• 11 المنشورات
  • 0 الصور
  • 0 الفيديوهات
  • Female
  • 12/12/1974
  • متابَع بواسطة 0 أشخاص
البحث
التحديثات الأخيرة

  • Interactions of multi-disciplines, reasonable coalesce between the medical treatment and theory, medical treatment and modern bioengineering techniques, as well as the integration of Chinese traditional and modern medicine will help promote the development of apparatuses of acupuncture-moxibustion for diagnosis and treatment of diseases. Such interdisciplinary efforts will make more contributions to the construction of healthy China and the health of all mankind.In recent years, the newly appeared closed-loop neuromodulation technique composed of closed-loop controlled stimulation system and neuromodulation is the product of medicine and inter-disciplines. In medical clinical practice, the idea of closed-loop controlled stimulation can be seen everywhere. When both the patient and acupuncturist achieve the state of "Deqi" simultaneously, it is a kind of feedback adjustment process similar to that of the closed-loop stimulation system. Cross-functional multidisciplinary development is the future trend of medical science progress. The acupuncture-moxibustion discipline can draw lessons from the research experience and achievements of closed-loop neuromodulation techniques to explore the origin of the compatibility of meridians, acupoints, and needling manipulations.Acupuncture-moxibustion, acupunctology and acupunctology discipline are three closely related concepts, with the first one being covered by the later one. In the present paper, we analyzed the formation, evolution and differentiation of acupunctology discipline and its significance. The knowledge system and academic institutions of acupuncture-moxibustion combine together to construct the acupunctology discipline. The introduction of interdisciplinary methods and academic perspectives is the core motivation of the formation, development and evolution of the acupunctology discipline, which not only enriches its problema-tic domains, but also interacts with the academically organizing force. The participation of interdiscipline promotes the broader and deeper development of the knowledge of acupunctology, and the knowledge expansion is also the inevitable result of infiltration of cross-disciplines. Hence, the maturity of the acupuntology discipline unavoidably leads to differentiation of the subject. At present, the acupunctology discipline can be divided into four main branches clinical acupuncture-moxibustion, techniques, mechanisms and humanities of acupuncture and moxibustion. Currently, the acupunctology subject has formed a direction of expansion in multiple dimensions of the knowledge system due to continuous collision, nourishment and infiltration from many other related disciplines. However, because it is from the classical learning, its knowledge system inevitably has the characteristics of inertial stability, insufficient motivation and vitality in breaking the traditional framework. These issues now need being faced up to and being solved at the moment.
    Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (**) has not yet been clarified.

    Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of ** cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays. Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p. Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting.

    NORAD expression was significantly reduced in ** cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed ** cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD.

    NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of ** cells.
    NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of ** cells.
    Trastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes.

    We retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group).

    Propensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%;
    = 0.002). https://www.selleckchem.com/products/shield-1.html The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07-8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer.

    Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.
    Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.
    Interactions of multi-disciplines, reasonable coalesce between the medical treatment and theory, medical treatment and modern bioengineering techniques, as well as the integration of Chinese traditional and modern medicine will help promote the development of apparatuses of acupuncture-moxibustion for diagnosis and treatment of diseases. Such interdisciplinary efforts will make more contributions to the construction of healthy China and the health of all mankind.In recent years, the newly appeared closed-loop neuromodulation technique composed of closed-loop controlled stimulation system and neuromodulation is the product of medicine and inter-disciplines. In medical clinical practice, the idea of closed-loop controlled stimulation can be seen everywhere. When both the patient and acupuncturist achieve the state of "Deqi" simultaneously, it is a kind of feedback adjustment process similar to that of the closed-loop stimulation system. Cross-functional multidisciplinary development is the future trend of medical science progress. The acupuncture-moxibustion discipline can draw lessons from the research experience and achievements of closed-loop neuromodulation techniques to explore the origin of the compatibility of meridians, acupoints, and needling manipulations.Acupuncture-moxibustion, acupunctology and acupunctology discipline are three closely related concepts, with the first one being covered by the later one. In the present paper, we analyzed the formation, evolution and differentiation of acupunctology discipline and its significance. The knowledge system and academic institutions of acupuncture-moxibustion combine together to construct the acupunctology discipline. The introduction of interdisciplinary methods and academic perspectives is the core motivation of the formation, development and evolution of the acupunctology discipline, which not only enriches its problema-tic domains, but also interacts with the academically organizing force. The participation of interdiscipline promotes the broader and deeper development of the knowledge of acupunctology, and the knowledge expansion is also the inevitable result of infiltration of cross-disciplines. Hence, the maturity of the acupuntology discipline unavoidably leads to differentiation of the subject. At present, the acupunctology discipline can be divided into four main branches clinical acupuncture-moxibustion, techniques, mechanisms and humanities of acupuncture and moxibustion. Currently, the acupunctology subject has formed a direction of expansion in multiple dimensions of the knowledge system due to continuous collision, nourishment and infiltration from many other related disciplines. However, because it is from the classical learning, its knowledge system inevitably has the characteristics of inertial stability, insufficient motivation and vitality in breaking the traditional framework. These issues now need being faced up to and being solved at the moment. Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays. Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p. Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells. NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells. Trastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes. We retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group). Propensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%; = 0.002). https://www.selleckchem.com/products/shield-1.html The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07-8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer. Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer. Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.
    0 التعليقات 0 المشاركات 245 مشاهدة 0 معاينة

  • Child malnutrition is a major epidemiological problem in developing countries, especially in African countries. Nutrition education for mothers can alleviate this malnutrition in their young children. https://www.selleckchem.com/products/triptolide.html The objective of this study was to make a systematic review to assess the effect of intervention programs in nutrition education for African mothers on the nutritional status of their infants.

    A bibliographic search was carried out in the PubMed database for clinical trials between November 2012 and 2021. The studies should contain educational programs to evaluate the impact on the infant's nutritional indicators in children under 5 years (food consumption, anthropometry and/or knowledge of nutrition in caretakers).

    A total of 20 articles were selected, of which 53% evaluated infant's food consumption, 82% anthropometric measurements and 30% nutritional knowledge. In general, nutritional education programs are accredited with some significant improvements in food and nutrient consumption, knowledge and dietary practices in complementary feeding, but only those studies that implemented strategies in agriculture, educational workshops and supplementation obtained reductions in chronic malnutrition figures.

    There is high heterogeneity in the articles included, since the intervention programs have different approaches.

    Programs that implemented actions of national agriculture or nutritional supplementation reap the greatest benefits in curbing infant malnutrition.
    Programs that implemented actions of national agriculture or nutritional supplementation reap the greatest benefits in curbing infant malnutrition.Increasing **** discomfort and spinal shrinkage during the workday is a problem that affects assembly line workers. The aim of this research was to analyze the effect of a spinal traction system on discomfort, spinal shrinkage, and spinal sagittal alignment in assembly line workers, who are in prolonged standing conditions during a workday. A total of 16 asymptomatic males were recruited to assess spinal shrinkage, spinal sagittal alignment, and **** discomfort during the workday. The measurement was carried out in two days of work, a normal day, and the other using a spinal traction device utilized in two breaks during the workday. Assembly line workers lost height significantly on both control and intervention days. No differences were found between days. No changes were found in spinal sagittal alignment on the control day. Lumbar lordosis angle increased significantly at the end of the intervention day. The use of a spinal traction device during the workday in two breaks time did not significantly reduce the spinal shrinkage of healthy workers. Lumbar lordosis angle increased significantly at the end of the spinal traction intervention day. Prospective studies would be necessary to clarify the possible benefits of the traction device.Studying abroad can be stressful due to culture shock and various other difficulties. However, with the current prevalence of information communication technology, we can surmise that study abroad difficulties should be minimal. Since it has been shown that an individual's personality is highly associated with their internet use behaviors, it would be interesting to determine the effects of personality traits on the relationship between internet use motives and perceived study abroad difficulties. Data were collected from 1870 volunteer study abroad students in Taiwan. Hierarchical regression analysis revealed that when controlling for the effects of age, gender, duration of stay, student status (short-term exchange or degree-seeking), and internet use motives (online benefits, habits, and facilitation), the personality trait neuroticism consistently showed significant relationships with the various study abroad difficulties. Moreover, moderation analyses revealed that all the personality traits except conscientiousness showed significant interactions with internet use, while simple slope comparisons showed significant differences between the high personality traits and their lower counterparts. In sum, an examination of the moderating role of personality traits in the relationship between internet use and study abroad difficulties may be useful for preemptively identifying at-risk students.Schizophrenia is associated with marked functional impairment and low levels of subjective happiness. The aim of the current study was to evaluate the relationship between subjective happiness and functioning in patients with schizophrenia, while considering the role of cognitive functioning.
    In total, 69 schizophrenia patients and 87 matched healthy controls participated in the study. Patients' clinical status was assessed, and a series of self-report questionnaires were administered to both patients and healthy controls to measure subjective happiness, satisfaction with life, well-being, functioning, and cognitive impairment. A multiple linear regression model identified significant predictors of subjective happiness and related constructs.

    Schizophrenia participants endorsed lower levels of happiness and well-being, and higher perceived stress compared to healthy controls. In schizophrenia patients, there was an inverse and significant correlation (r = -0.435;
    = 0.013) between subjective happiness anzophrenia.
    The relationship between subjective happiness and functioning in schizophrenia patients was influenced by level of cognitive impairment. Findings from this study suggest that rehabilitation programs may improve recovery outcomes with a focus on subjective happiness and functioning, especially in patients with cognitive impairment. Future research is needed to better understand the complex interplay between subjective happiness, functioning, and cognitive impairment in patients with schizophrenia.Active ageing can lead to better health outcomes in older people. Examining constraints to outdoor recreation for older people, including outdoor physical activity, may therefore assist with developing strategies for active ageing. Findings are presented from a study seeking to understand the constraints to older peoples' access to outdoor recreation in Scotland, and this paper aimed to examine the multitude of constraints that discourage or prevent older people from accessing the outdoors and the ways in which these constraints are hierarchical (or not). This paper adopted a qualitative methodology using the hierarchical leisure constraints model (HLCM) as a lens to analyse the data, presenting the data in three vignettes. The paper identified multiple co-occurring constraints and considered these in relation to expectations based on the HLCM. Recognising that constraints to outdoor recreation for older people are multiple, co-occurring and mutually reinforcing may enable more effective solutions to be developed to overcome them.
    Child malnutrition is a major epidemiological problem in developing countries, especially in African countries. Nutrition education for mothers can alleviate this malnutrition in their young children. https://www.selleckchem.com/products/triptolide.html The objective of this study was to make a systematic review to assess the effect of intervention programs in nutrition education for African mothers on the nutritional status of their infants. A bibliographic search was carried out in the PubMed database for clinical trials between November 2012 and 2021. The studies should contain educational programs to evaluate the impact on the infant's nutritional indicators in children under 5 years (food consumption, anthropometry and/or knowledge of nutrition in caretakers). A total of 20 articles were selected, of which 53% evaluated infant's food consumption, 82% anthropometric measurements and 30% nutritional knowledge. In general, nutritional education programs are accredited with some significant improvements in food and nutrient consumption, knowledge and dietary practices in complementary feeding, but only those studies that implemented strategies in agriculture, educational workshops and supplementation obtained reductions in chronic malnutrition figures. There is high heterogeneity in the articles included, since the intervention programs have different approaches. Programs that implemented actions of national agriculture or nutritional supplementation reap the greatest benefits in curbing infant malnutrition. Programs that implemented actions of national agriculture or nutritional supplementation reap the greatest benefits in curbing infant malnutrition.Increasing back discomfort and spinal shrinkage during the workday is a problem that affects assembly line workers. The aim of this research was to analyze the effect of a spinal traction system on discomfort, spinal shrinkage, and spinal sagittal alignment in assembly line workers, who are in prolonged standing conditions during a workday. A total of 16 asymptomatic males were recruited to assess spinal shrinkage, spinal sagittal alignment, and back discomfort during the workday. The measurement was carried out in two days of work, a normal day, and the other using a spinal traction device utilized in two breaks during the workday. Assembly line workers lost height significantly on both control and intervention days. No differences were found between days. No changes were found in spinal sagittal alignment on the control day. Lumbar lordosis angle increased significantly at the end of the intervention day. The use of a spinal traction device during the workday in two breaks time did not significantly reduce the spinal shrinkage of healthy workers. Lumbar lordosis angle increased significantly at the end of the spinal traction intervention day. Prospective studies would be necessary to clarify the possible benefits of the traction device.Studying abroad can be stressful due to culture shock and various other difficulties. However, with the current prevalence of information communication technology, we can surmise that study abroad difficulties should be minimal. Since it has been shown that an individual's personality is highly associated with their internet use behaviors, it would be interesting to determine the effects of personality traits on the relationship between internet use motives and perceived study abroad difficulties. Data were collected from 1870 volunteer study abroad students in Taiwan. Hierarchical regression analysis revealed that when controlling for the effects of age, gender, duration of stay, student status (short-term exchange or degree-seeking), and internet use motives (online benefits, habits, and facilitation), the personality trait neuroticism consistently showed significant relationships with the various study abroad difficulties. Moreover, moderation analyses revealed that all the personality traits except conscientiousness showed significant interactions with internet use, while simple slope comparisons showed significant differences between the high personality traits and their lower counterparts. In sum, an examination of the moderating role of personality traits in the relationship between internet use and study abroad difficulties may be useful for preemptively identifying at-risk students.Schizophrenia is associated with marked functional impairment and low levels of subjective happiness. The aim of the current study was to evaluate the relationship between subjective happiness and functioning in patients with schizophrenia, while considering the role of cognitive functioning. In total, 69 schizophrenia patients and 87 matched healthy controls participated in the study. Patients' clinical status was assessed, and a series of self-report questionnaires were administered to both patients and healthy controls to measure subjective happiness, satisfaction with life, well-being, functioning, and cognitive impairment. A multiple linear regression model identified significant predictors of subjective happiness and related constructs. Schizophrenia participants endorsed lower levels of happiness and well-being, and higher perceived stress compared to healthy controls. In schizophrenia patients, there was an inverse and significant correlation (r = -0.435; = 0.013) between subjective happiness anzophrenia. The relationship between subjective happiness and functioning in schizophrenia patients was influenced by level of cognitive impairment. Findings from this study suggest that rehabilitation programs may improve recovery outcomes with a focus on subjective happiness and functioning, especially in patients with cognitive impairment. Future research is needed to better understand the complex interplay between subjective happiness, functioning, and cognitive impairment in patients with schizophrenia.Active ageing can lead to better health outcomes in older people. Examining constraints to outdoor recreation for older people, including outdoor physical activity, may therefore assist with developing strategies for active ageing. Findings are presented from a study seeking to understand the constraints to older peoples' access to outdoor recreation in Scotland, and this paper aimed to examine the multitude of constraints that discourage or prevent older people from accessing the outdoors and the ways in which these constraints are hierarchical (or not). This paper adopted a qualitative methodology using the hierarchical leisure constraints model (HLCM) as a lens to analyse the data, presenting the data in three vignettes. The paper identified multiple co-occurring constraints and considered these in relation to expectations based on the HLCM. Recognising that constraints to outdoor recreation for older people are multiple, co-occurring and mutually reinforcing may enable more effective solutions to be developed to overcome them.
    0 التعليقات 0 المشاركات 127 مشاهدة 0 معاينة

  • Periodontal disease continues to be prevalent globally, but little clinical research has been undertaken to evaluate the long-term benefits of a daily oral hygiene regimen on progression of gingivitis/early periodontitis. The objective of this study was to evaluate the effects of an oral hygiene regimen (OHR) on the periodontal health of adults in good general health with established gingivitis and early periodontitis over 24 months.

    A randomized controlled trial was conducted in adults with established gingivitis, with isolated sites of probing pocket depth >4 mm. Study participants were randomized to the OHR (bioavailable stannous fluoride dentifrice, oscillating-rotating electric toothbrush, cetylpyridinium chloride rinse, and floss; P&G) or usual care products (sodium fluoride dentifrice and manual toothbrush; P&G) groups. At baseline and every 6 months, gingivitis and periodontal measures were assessed and a prophylaxis was conducted. The primary outcome was Gingival Bleeding Index-Bleeding Sites (GBI-BS). Analyses used ANCOVA at 5% significance levels.

    A total of 107 individuals were enrolled; 87 completed the study. Mean GBI-BS, Modified Gingival Index, and Probing Pocket Depth (PPD) scores were significantly lower at each visit for the OHR versus usual care group by 28% to 39%, 12% to 18%, and 6% to 13%, respectively (
    ≤ 0.0009). The magnitude of reduction in median number of ≥2 mm PPD loss events for OHR versus the usual care group at 24 months was 74%.

    Long-term use of the OHR produced significant periodontal health improvements versus the usual care products.
    Long-term use of the OHR produced significant periodontal health improvements versus the usual care products.
    Antibiotic resistance in bacteria is a major global health challenge. Reports on the prevalence of multidrug-resistant
    a common pathogenic bacterium implicated in nosocomial infections and poultry diseases, are limited in Ghana. This study therefore sought to determine the prevalence of
    from hospitals, poultry farms, and environmental samples from the Ashanti region of Ghana.
    . Stool, urine, and blood samples from 364 patients from two hospitals
    were randomly sampled
    was isolated and confirmed using routine selective media and PCR-based
    gene amplification. The Kirby-Bauer disk diffusion method employing EUCAST breakpoint values was used to identify multidrug-resistant strains. The occurrence of common antibiotic inactivating enzymes and resistance encoding genes and the assessment of strain efflux capacity were investigated with double disc synergy test (DDST), imipenem-EDTA synergy test, phenylboronic acid test, D-test, routine PCR, and ethidium bromide agar-cartwheel method.

    A total of 87 (9.7%,
     = 87/900)
    isolates were confirmed from the samples. 75% (
     = 65/87) were resistant to more than one group of antipseudomonal agents, while 43.6% (
     = 38/87) were multidrug-resistant (MDR). High prevalence of extended spectrum
    -lactamases (84.2%), metallo-
    -lactamases (34.1%), and AmpC inducible cephalosporinases (50%) was observed in the MDR strains. About 57.8% of the MDR strains showed moderate to very high efflux capacity. Class 1 integrons were detected in 89.4% of the MDR isolates but
    -lactamase encoding genes (

    ,

    ,

    ,

    , and

    ) were not detected.

    Surveillance of antibiotic-resistant strains of bacteria should be routinely conducted in clinical and veterinary practice in Ghana to inform selection of antibiotics for therapeutic use.
    Surveillance of antibiotic-resistant strains of bacteria should be routinely conducted in clinical and veterinary practice in Ghana to inform selection of antibiotics for therapeutic use.
    To promote oral health in society, medical and nursing students are required to have acceptable knowledge, attitude, and practice with respect to correct maintenance and use of a toothbrush. This study explored the knowledge, attitude, and practice of Iranian medical and nursing students about the correct maintenance and use of a toothbrush.

    A total of 260 nursing students and 320 medical students were randomly recruited. Data were collected by a researcher-made questionnaire on the knowledge, attitude, and practice about toothbrush maintenance and use. Data were analyzed using descriptive and inferential statistics.

    The mean scores of knowledge, attitude, and practice were 54.53 ± 17.18, 49.67 ± 19.17, and 19 ± 51.50 in the nursing students and 54.17 ± 21.42, 51.18 ± 87.28, and 49.87 ± 17.52 out of 100 in the medical students, respectively. There was no significant difference between the medical and nursing students in the mean score of knowledge. The medical and nursing students had a similar attitude and practice in most items of toothbrush maintenance and use.

    The medical and nursing students had average knowledge, attitude, and practice regarding toothbrush maintenance and use, which is not acceptable considering their job nature. Hence, interventional measures should be taken to enhance their knowledge, attitude, and practice.
    The medical and nursing students had average knowledge, attitude, and practice regarding toothbrush maintenance and use, which is not acceptable considering their job nature. Hence, interventional measures should be taken to enhance their knowledge, attitude, and practice.Malaria remains a major public health problem in Cameroon. Critical steps to improve disease control include assessing human population adherence to vector control interventions, especially in areas with different cultural backgrounds. The present study seeks to assess the knowledge, attitude, and practices (KAP) of populations towards malaria prevention in four ecoepidemiological settings in Cameroon. A cross-sectional malaria KAP survey was conducted from August to September 2019 in households of the localities of Kaélé, Tibati, Bertoua, and Santchou. A semistructured questionnaire was administered to randomly selected households in the localities. Data recorded were analysed using SPSS v. 20 and MedCalc v14.8.1. A total of 739 households were surveyed. The majority of participants had a secondary level of education (48.71%). https://www.selleckchem.com/products/U0126.html A substantial number of participants (over 90%) in all the localities were able to make an accurate association between malaria and mosquito bites. The main sources of information for community members were television sets in Santchou and Tibati and interpersonal conversations in Bertoua and Kaélé.
    Periodontal disease continues to be prevalent globally, but little clinical research has been undertaken to evaluate the long-term benefits of a daily oral hygiene regimen on progression of gingivitis/early periodontitis. The objective of this study was to evaluate the effects of an oral hygiene regimen (OHR) on the periodontal health of adults in good general health with established gingivitis and early periodontitis over 24 months. A randomized controlled trial was conducted in adults with established gingivitis, with isolated sites of probing pocket depth >4 mm. Study participants were randomized to the OHR (bioavailable stannous fluoride dentifrice, oscillating-rotating electric toothbrush, cetylpyridinium chloride rinse, and floss; P&G) or usual care products (sodium fluoride dentifrice and manual toothbrush; P&G) groups. At baseline and every 6 months, gingivitis and periodontal measures were assessed and a prophylaxis was conducted. The primary outcome was Gingival Bleeding Index-Bleeding Sites (GBI-BS). Analyses used ANCOVA at 5% significance levels. A total of 107 individuals were enrolled; 87 completed the study. Mean GBI-BS, Modified Gingival Index, and Probing Pocket Depth (PPD) scores were significantly lower at each visit for the OHR versus usual care group by 28% to 39%, 12% to 18%, and 6% to 13%, respectively ( ≤ 0.0009). The magnitude of reduction in median number of ≥2 mm PPD loss events for OHR versus the usual care group at 24 months was 74%. Long-term use of the OHR produced significant periodontal health improvements versus the usual care products. Long-term use of the OHR produced significant periodontal health improvements versus the usual care products. Antibiotic resistance in bacteria is a major global health challenge. Reports on the prevalence of multidrug-resistant a common pathogenic bacterium implicated in nosocomial infections and poultry diseases, are limited in Ghana. This study therefore sought to determine the prevalence of from hospitals, poultry farms, and environmental samples from the Ashanti region of Ghana. . Stool, urine, and blood samples from 364 patients from two hospitals were randomly sampled was isolated and confirmed using routine selective media and PCR-based gene amplification. The Kirby-Bauer disk diffusion method employing EUCAST breakpoint values was used to identify multidrug-resistant strains. The occurrence of common antibiotic inactivating enzymes and resistance encoding genes and the assessment of strain efflux capacity were investigated with double disc synergy test (DDST), imipenem-EDTA synergy test, phenylboronic acid test, D-test, routine PCR, and ethidium bromide agar-cartwheel method. A total of 87 (9.7%,  = 87/900) isolates were confirmed from the samples. 75% (  = 65/87) were resistant to more than one group of antipseudomonal agents, while 43.6% (  = 38/87) were multidrug-resistant (MDR). High prevalence of extended spectrum -lactamases (84.2%), metallo- -lactamases (34.1%), and AmpC inducible cephalosporinases (50%) was observed in the MDR strains. About 57.8% of the MDR strains showed moderate to very high efflux capacity. Class 1 integrons were detected in 89.4% of the MDR isolates but -lactamase encoding genes ( , , , , and ) were not detected. Surveillance of antibiotic-resistant strains of bacteria should be routinely conducted in clinical and veterinary practice in Ghana to inform selection of antibiotics for therapeutic use. Surveillance of antibiotic-resistant strains of bacteria should be routinely conducted in clinical and veterinary practice in Ghana to inform selection of antibiotics for therapeutic use. To promote oral health in society, medical and nursing students are required to have acceptable knowledge, attitude, and practice with respect to correct maintenance and use of a toothbrush. This study explored the knowledge, attitude, and practice of Iranian medical and nursing students about the correct maintenance and use of a toothbrush. A total of 260 nursing students and 320 medical students were randomly recruited. Data were collected by a researcher-made questionnaire on the knowledge, attitude, and practice about toothbrush maintenance and use. Data were analyzed using descriptive and inferential statistics. The mean scores of knowledge, attitude, and practice were 54.53 ± 17.18, 49.67 ± 19.17, and 19 ± 51.50 in the nursing students and 54.17 ± 21.42, 51.18 ± 87.28, and 49.87 ± 17.52 out of 100 in the medical students, respectively. There was no significant difference between the medical and nursing students in the mean score of knowledge. The medical and nursing students had a similar attitude and practice in most items of toothbrush maintenance and use. The medical and nursing students had average knowledge, attitude, and practice regarding toothbrush maintenance and use, which is not acceptable considering their job nature. Hence, interventional measures should be taken to enhance their knowledge, attitude, and practice. The medical and nursing students had average knowledge, attitude, and practice regarding toothbrush maintenance and use, which is not acceptable considering their job nature. Hence, interventional measures should be taken to enhance their knowledge, attitude, and practice.Malaria remains a major public health problem in Cameroon. Critical steps to improve disease control include assessing human population adherence to vector control interventions, especially in areas with different cultural backgrounds. The present study seeks to assess the knowledge, attitude, and practices (KAP) of populations towards malaria prevention in four ecoepidemiological settings in Cameroon. A cross-sectional malaria KAP survey was conducted from August to September 2019 in households of the localities of Kaélé, Tibati, Bertoua, and Santchou. A semistructured questionnaire was administered to randomly selected households in the localities. Data recorded were analysed using SPSS v. 20 and MedCalc v14.8.1. A total of 739 households were surveyed. The majority of participants had a secondary level of education (48.71%). https://www.selleckchem.com/products/U0126.html A substantial number of participants (over 90%) in all the localities were able to make an accurate association between malaria and mosquito bites. The main sources of information for community members were television sets in Santchou and Tibati and interpersonal conversations in Bertoua and Kaélé.
    0 التعليقات 0 المشاركات 107 مشاهدة 0 معاينة

  • The study aimed to investigate the effects of vitamin E injection for the prevention of transport stress on ewes. Kivircik ewes (2-3 years old, n = 24) were randomly separated into three groups; G1 (Control) and G2 treated with 14 ml. saline as the placebo, G3 treated with 2100 IU/ind. DL-alpha-tocopherol acetate prior to transport. G2 and G3 were transported at 80 km/h for 4 h on a truck. https://www.selleckchem.com/products/ro-3306.html Serum samples were obtained before (T0) and after (T1) transport. Serum cortisol, catalase, IgG, ceruloplasmin, C-reactive protein, complement component 4, interleukin-1 beta, tumour necrosis factor-alpha, glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde analyses performed by ELISA, and serum alpha-tocopherol concentrations were evaluated by HPLC-UV. Wilcoxon and Kruskal-Wallis tests were used for statistical assessments (p less then 0.05). Alpha-tocopherol concentrations were founded 1.22 ± 0.82, 0.27 ± 0.14 and 0.14 ± 0.07 µmol/L, respectively, in G1, G2 and G3 at T1. Alpha-tocopherol concentration decreased significantly in G2 between T0 and T1. GPx concentrations were increased twofold in G2 and G3 between T0 and T1 (p less then 0.01). As a result, G2 alpha-tocopherol concentrations decreased but, the stress and oxidative parameters tested in this study were not affected by treating 2100 IU/ind. DL-alpha-tocopherol acetate before transport.Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let-7c, miR-26b-5p, -29c-3p, -148a-3p, -196a-5p, -199b-5p and -374a-5p suppressed in iPSC-derived fibroblasts in vitro and in 3D dermis-like self-assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC-derived fibroblasts and was confirmed as a direct target of miR-196a-5p. miR-197-3p and miR-331-3p were found upregulated specifically in iPSC-derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR-197-3p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non-healing miR-mediated epigenetic signature and promoting a pro-healing cellular phenotype.A nickel-catalyzed thiolation of aryl nitriles has been developed to access functionalized aryl thioethers. The ligand dcype (1,2-bis(dicyclohexylphosphino)ethane) as well as the base KOt Bu (potassium tert-butoxide) are essential to achieve this transformation. This scalable and practical process involves both a C-C bond activation and a C-S bond formation. Furthermore, this reaction shows a high functional-group tolerance and enables the late-stage functionalization of important molecules.
    Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance.

    Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo.

    We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdownerapy.
    Adverse reactions to food are a common dermatological condition in dogs, requiring nutritional intervention using novel or hydrolysate protein-based foods.

    To evaluate a therapeutic food containing egg and phytonutrients in dogs with food allergies using an activity monitor and core outcome set for canine atopic dermatitis (COSCAD'18) in a controlled double-masked, multicenter, prospective clinical trial.

    Adult dogs with a history of adverse food reaction as diagnosed by a food elimination trial were recruited from general practices.

    After a 21-day baseline period, dogs were randomized to test or positive control (hydrolyzed protein) food for 21 days. Owner (pruritus visual analog score [PVAS], coat quality, food acceptance, and satisfaction) and veterinarian (canine atopic dermatitis lesion index [CADLI], physical examination) assessments were completed on days 0, 21, and 42. Dogs wore a collar-mounted activity monitor to record sleep, scratching, and shaking behavior throughout the study. Statistical analysis included within-group comparison to baseline and between-group comparison at study end using a significance threshold of alpha=0.05.

    At the end of the treatment period, all results were similar between groups for CADLI, PVAS, owner satisfaction, activity, and questionnaire data. Scores for hair dullness, brittleness, amount of dandruff, feces quality, and food acceptance were positive and were not statistically different between groups.

    The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food.
    The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food.
    The study aimed to investigate the effects of vitamin E injection for the prevention of transport stress on ewes. Kivircik ewes (2-3 years old, n = 24) were randomly separated into three groups; G1 (Control) and G2 treated with 14 ml. saline as the placebo, G3 treated with 2100 IU/ind. DL-alpha-tocopherol acetate prior to transport. G2 and G3 were transported at 80 km/h for 4 h on a truck. https://www.selleckchem.com/products/ro-3306.html Serum samples were obtained before (T0) and after (T1) transport. Serum cortisol, catalase, IgG, ceruloplasmin, C-reactive protein, complement component 4, interleukin-1 beta, tumour necrosis factor-alpha, glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde analyses performed by ELISA, and serum alpha-tocopherol concentrations were evaluated by HPLC-UV. Wilcoxon and Kruskal-Wallis tests were used for statistical assessments (p less then 0.05). Alpha-tocopherol concentrations were founded 1.22 ± 0.82, 0.27 ± 0.14 and 0.14 ± 0.07 µmol/L, respectively, in G1, G2 and G3 at T1. Alpha-tocopherol concentration decreased significantly in G2 between T0 and T1. GPx concentrations were increased twofold in G2 and G3 between T0 and T1 (p less then 0.01). As a result, G2 alpha-tocopherol concentrations decreased but, the stress and oxidative parameters tested in this study were not affected by treating 2100 IU/ind. DL-alpha-tocopherol acetate before transport.Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let-7c, miR-26b-5p, -29c-3p, -148a-3p, -196a-5p, -199b-5p and -374a-5p suppressed in iPSC-derived fibroblasts in vitro and in 3D dermis-like self-assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC-derived fibroblasts and was confirmed as a direct target of miR-196a-5p. miR-197-3p and miR-331-3p were found upregulated specifically in iPSC-derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR-197-3p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non-healing miR-mediated epigenetic signature and promoting a pro-healing cellular phenotype.A nickel-catalyzed thiolation of aryl nitriles has been developed to access functionalized aryl thioethers. The ligand dcype (1,2-bis(dicyclohexylphosphino)ethane) as well as the base KOt Bu (potassium tert-butoxide) are essential to achieve this transformation. This scalable and practical process involves both a C-C bond activation and a C-S bond formation. Furthermore, this reaction shows a high functional-group tolerance and enables the late-stage functionalization of important molecules. Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance. Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo. We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdownerapy. Adverse reactions to food are a common dermatological condition in dogs, requiring nutritional intervention using novel or hydrolysate protein-based foods. To evaluate a therapeutic food containing egg and phytonutrients in dogs with food allergies using an activity monitor and core outcome set for canine atopic dermatitis (COSCAD'18) in a controlled double-masked, multicenter, prospective clinical trial. Adult dogs with a history of adverse food reaction as diagnosed by a food elimination trial were recruited from general practices. After a 21-day baseline period, dogs were randomized to test or positive control (hydrolyzed protein) food for 21 days. Owner (pruritus visual analog score [PVAS], coat quality, food acceptance, and satisfaction) and veterinarian (canine atopic dermatitis lesion index [CADLI], physical examination) assessments were completed on days 0, 21, and 42. Dogs wore a collar-mounted activity monitor to record sleep, scratching, and shaking behavior throughout the study. Statistical analysis included within-group comparison to baseline and between-group comparison at study end using a significance threshold of alpha=0.05. At the end of the treatment period, all results were similar between groups for CADLI, PVAS, owner satisfaction, activity, and questionnaire data. Scores for hair dullness, brittleness, amount of dandruff, feces quality, and food acceptance were positive and were not statistically different between groups. The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food. The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food.
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  • Aim Since 2012 and to date, outbreak/new cases of Middle East respiratory syndrome-related coronavirus (MERS-CoV) were always reported in Saudi Arabia. Al-Jouf region is considered as one of the most vulnerable areas to the disease outbreak. This research aimed to assess (to the best of our knowledge), for the first time, the current level of awareness towards MERS-CoV among the Al-Jouf region population through a well-designed multistage questionnaire. Subjects and methods A cross-sectional study of 384 participants recruited from various places in Al-Jouf government was conducted through a valid and reliable questionnaire including sociodemographic and MERS-CoV knowledge data. Results The majority of the participants showed generally moderate knowledge about MERS-CoV. https://www.selleckchem.com/products/Cyclosporin-A(Cyclosporine-A).html Age, education, and occupation were the only significant predictors of the level of low awareness concern. Also, the public awareness about the nature, communicability, and lethal effect of the disease was good overall; however, knowledge about incubation period, clinical picture, and epidemiology of the disease needs more governmental concern. The Ministry of Health was the main source of information. Conclusion Empowering public information regarding the incubation period and epidemiology of the disease is needed. Frequent communication between healthcare providers and both school students and non-educated individuals is recommended to help the Saudi government in controlling the disease outbreak. © Springer-Verlag GmbH Germany, part of Springer Nature 2020.Coronary artery perforation secondary to percutaneous coronary intervention (PCI) is a rare, but a potentially life-threatening complication. There is a misconception that cardiac tamponade rarely occurs in patients with prior coronary artery bypass grafting (CABG). We first describe a giant right ventricular intramural hematoma following PCI via a saphenous vein graft to treat a distal stenosis of the right coronary artery, and its successful treatment with redo cardiac surgery. Complex elective PCIs on patients after CABG should be performed in specialized centers with a well-established heart team that has the expertise to treat any of the potential complications.Coronary artery fistulae are an incidental finding in patients undergoing coronary angiography or computed tomography (CT) coronary angiography. A 60-year-old man with known coronary artery disease presented with dyspnea. Coronary angiography revealed a large fistula arising from the circumflex artery (CX) without a clear intrathoracic target vessel or chamber in the heart. CT angiography revealed the agenesis of the left pulmonary artery. The fistula arising from the CX ensured left lung tissue supply. Unilateral absence of a pulmonary artery is an extremely rare condition. In this case, the identification of a fistula from the heart triggered the correct diagnosis.Introduction  Textiloma (Txm) is a nonmedical term that has been given to foreign body-related inflammatory pseudotumor arising from retained nonabsorbable cotton matrix that is either inadvertently or deliberately left behind during surgery, which may trigger an inflammatory reaction. This report describes a case of Txm mimicking a recurrent high-grade astrocytoma. Case Report  We, here, present the case of a 69-year-old female with a 6-month history of progressive left-sided weakness. Neuroimaging studies revealed a large nonenhancing mass in the right frontoparietal lobe. Pathology reported a World Health Organization tumor classification grade II, diffuse astrocytoma. After surgical intervention, external beam radiation was given to the remaining areas of residual tumor. Routine magnetic resonance imaging (MRI) revealed a nodular area of contrast enhancement in the dorsal and inferior margin of the biopsy tract, growing between interval scans, and perfusion-weighted imaging parameters were elevated being clinically asymptomatic. She underwent a complete resection of this area of interest and pathology returned as a Txm with Surgicel fibers. Conclusion  After treatment of a neoplasm, if unexpected clinical or imaging evidence of recurrence is present, a foreign body reaction to hemostatic material used during the initial surgery should be included in the differential diagnosis.Background  Thirty-day readmission has become a significant health care metric reflecting the quality of care and on the cost of service delivery. There is little data on the impact of complications following skull base surgery (SBS) on emergency readmission. Identifying modifiable risk factors for readmission may improve care and reduce cost. Design  The study was designed as a single-center retrospective cohort study. Methods  Records for a consecutive series of 165 patients who underwent open or endoscopic SBS by a single surgeon reviewed. Patients with pituitary adenoma were excluded. The diagnosis, procedure, complications, length of stay (LOS), body mass index (BMI), and smoking status were recorded. Readmission to the neurosurgical department or regional hospitals was either noted prospectively or the patient contacted. Cause and length of readmission was documented. Results  Of the 165 cases, 14 (8.5%) were readmitted within 30 days. Causes for readmission included cerebrospinal fluid (CSF) leak in 5/14 or 35.7% (overall rate for readmission for this complication in the series is 3.1%), infection in 4/14 (28.6%), hyponatraemia in 2/14 (14.3%), vascular sinus thrombosis in 1/14 (7.1%), seizures in 1/14 (7.1%), and epistaxis in 1/14 (7.1%). Initial and readmission LOS was 6 and 14 days, respectively. BMI was higher in those readmitted within 30 days (33.2 kg/m 2 ) versus no readmission (27.1 kg/m 2 ). In addition, of those readmitted within 30 days, 35.7% were smokers compared with 20.8% in those not readmitted. Conclusion  In this series, smoking and raised BMI may be indicators for within 30-day readmission and complications in this population, raising the question of risk factor modification prior to elective intervention. © Thieme Medical Publishers.Objectives  The aim of this study was to analyze the effect of the multimodality treatment on survival in sinonasal minor salivary gland tumors. Methods  Adult clinical American Joint Committee on Cancer (AJCC) tumor (T) 1-4a staged cases of sinonasal minor salivary gland tumors were isolated from the National Cancer Database (2004-2014). Multivariate regressions were performed to analyze the effect of multimodality treatment. A subset analysis was also performed in patients with positive margins following surgical management. Results  We identified 556 cases, of which 293 (52.7%) patients were treated with surgery and radiotherapy (RT), 160 (28.8%) were treated with surgery alone, and 52 (9.4%) were treated with surgery and chemoradiotherapy (CRT). No patients were treated with chemotherapy alone. With surgery and CRT as a reference, the only treatment modality associated with decreased survival was RT alone (hazard ratio [HR] 3.213 [95% confidence interval (CI) 1.578-6.543]; p  = 0.001). Within a subset analysis of patients with positive margins, surgery was associated with decreased survival (HR 2.
    Aim Since 2012 and to date, outbreak/new cases of Middle East respiratory syndrome-related coronavirus (MERS-CoV) were always reported in Saudi Arabia. Al-Jouf region is considered as one of the most vulnerable areas to the disease outbreak. This research aimed to assess (to the best of our knowledge), for the first time, the current level of awareness towards MERS-CoV among the Al-Jouf region population through a well-designed multistage questionnaire. Subjects and methods A cross-sectional study of 384 participants recruited from various places in Al-Jouf government was conducted through a valid and reliable questionnaire including sociodemographic and MERS-CoV knowledge data. Results The majority of the participants showed generally moderate knowledge about MERS-CoV. https://www.selleckchem.com/products/Cyclosporin-A(Cyclosporine-A).html Age, education, and occupation were the only significant predictors of the level of low awareness concern. Also, the public awareness about the nature, communicability, and lethal effect of the disease was good overall; however, knowledge about incubation period, clinical picture, and epidemiology of the disease needs more governmental concern. The Ministry of Health was the main source of information. Conclusion Empowering public information regarding the incubation period and epidemiology of the disease is needed. Frequent communication between healthcare providers and both school students and non-educated individuals is recommended to help the Saudi government in controlling the disease outbreak. © Springer-Verlag GmbH Germany, part of Springer Nature 2020.Coronary artery perforation secondary to percutaneous coronary intervention (PCI) is a rare, but a potentially life-threatening complication. There is a misconception that cardiac tamponade rarely occurs in patients with prior coronary artery bypass grafting (CABG). We first describe a giant right ventricular intramural hematoma following PCI via a saphenous vein graft to treat a distal stenosis of the right coronary artery, and its successful treatment with redo cardiac surgery. Complex elective PCIs on patients after CABG should be performed in specialized centers with a well-established heart team that has the expertise to treat any of the potential complications.Coronary artery fistulae are an incidental finding in patients undergoing coronary angiography or computed tomography (CT) coronary angiography. A 60-year-old man with known coronary artery disease presented with dyspnea. Coronary angiography revealed a large fistula arising from the circumflex artery (CX) without a clear intrathoracic target vessel or chamber in the heart. CT angiography revealed the agenesis of the left pulmonary artery. The fistula arising from the CX ensured left lung tissue supply. Unilateral absence of a pulmonary artery is an extremely rare condition. In this case, the identification of a fistula from the heart triggered the correct diagnosis.Introduction  Textiloma (Txm) is a nonmedical term that has been given to foreign body-related inflammatory pseudotumor arising from retained nonabsorbable cotton matrix that is either inadvertently or deliberately left behind during surgery, which may trigger an inflammatory reaction. This report describes a case of Txm mimicking a recurrent high-grade astrocytoma. Case Report  We, here, present the case of a 69-year-old female with a 6-month history of progressive left-sided weakness. Neuroimaging studies revealed a large nonenhancing mass in the right frontoparietal lobe. Pathology reported a World Health Organization tumor classification grade II, diffuse astrocytoma. After surgical intervention, external beam radiation was given to the remaining areas of residual tumor. Routine magnetic resonance imaging (MRI) revealed a nodular area of contrast enhancement in the dorsal and inferior margin of the biopsy tract, growing between interval scans, and perfusion-weighted imaging parameters were elevated being clinically asymptomatic. She underwent a complete resection of this area of interest and pathology returned as a Txm with Surgicel fibers. Conclusion  After treatment of a neoplasm, if unexpected clinical or imaging evidence of recurrence is present, a foreign body reaction to hemostatic material used during the initial surgery should be included in the differential diagnosis.Background  Thirty-day readmission has become a significant health care metric reflecting the quality of care and on the cost of service delivery. There is little data on the impact of complications following skull base surgery (SBS) on emergency readmission. Identifying modifiable risk factors for readmission may improve care and reduce cost. Design  The study was designed as a single-center retrospective cohort study. Methods  Records for a consecutive series of 165 patients who underwent open or endoscopic SBS by a single surgeon reviewed. Patients with pituitary adenoma were excluded. The diagnosis, procedure, complications, length of stay (LOS), body mass index (BMI), and smoking status were recorded. Readmission to the neurosurgical department or regional hospitals was either noted prospectively or the patient contacted. Cause and length of readmission was documented. Results  Of the 165 cases, 14 (8.5%) were readmitted within 30 days. Causes for readmission included cerebrospinal fluid (CSF) leak in 5/14 or 35.7% (overall rate for readmission for this complication in the series is 3.1%), infection in 4/14 (28.6%), hyponatraemia in 2/14 (14.3%), vascular sinus thrombosis in 1/14 (7.1%), seizures in 1/14 (7.1%), and epistaxis in 1/14 (7.1%). Initial and readmission LOS was 6 and 14 days, respectively. BMI was higher in those readmitted within 30 days (33.2 kg/m 2 ) versus no readmission (27.1 kg/m 2 ). In addition, of those readmitted within 30 days, 35.7% were smokers compared with 20.8% in those not readmitted. Conclusion  In this series, smoking and raised BMI may be indicators for within 30-day readmission and complications in this population, raising the question of risk factor modification prior to elective intervention. © Thieme Medical Publishers.Objectives  The aim of this study was to analyze the effect of the multimodality treatment on survival in sinonasal minor salivary gland tumors. Methods  Adult clinical American Joint Committee on Cancer (AJCC) tumor (T) 1-4a staged cases of sinonasal minor salivary gland tumors were isolated from the National Cancer Database (2004-2014). Multivariate regressions were performed to analyze the effect of multimodality treatment. A subset analysis was also performed in patients with positive margins following surgical management. Results  We identified 556 cases, of which 293 (52.7%) patients were treated with surgery and radiotherapy (RT), 160 (28.8%) were treated with surgery alone, and 52 (9.4%) were treated with surgery and chemoradiotherapy (CRT). No patients were treated with chemotherapy alone. With surgery and CRT as a reference, the only treatment modality associated with decreased survival was RT alone (hazard ratio [HR] 3.213 [95% confidence interval (CI) 1.578-6.543]; p  = 0.001). Within a subset analysis of patients with positive margins, surgery was associated with decreased survival (HR 2.
    0 التعليقات 0 المشاركات 122 مشاهدة 0 معاينة

  • 0%), and ventilation mode was changed for 11 patients (4.10%) during transport.

    The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making.
    The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making.
    The pressure within an endotracheal tube cuff is of particular importance in helicopter emergency medical services (HEMS) transport because the unpressurized cabin is subjected to decreases in atmospheric pressure. This can cause the cuff to overinflate and may be associated with clinical complications. We sought to evaluate endotracheal tube cuff pressure changes among intubated patients during HEMS transport.

    A prospective observational study was performed including adult patients who were intubated and transported by helicopter between April 2017 and October 2018. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Cuff pressures were measured before, during, and after HEMS transport with a commercial manometer.

    A total of 208 patients were included. The median maximum flight altitude was 3,000 (interquartile range [IQR], 2,000-5,000) ft. The median initial cuff pressure before takeoff was 35 (IQR, 24-50) cm H
    O, which increased to 50 (IQR, 35-70) cm H
    O at maximum altitude. A total of 169 (81.3%) patients had a cuff pressure > 30 cm H
    O at maximum altitude. There was a moderate correlation between altitude and cuff pressure (r = 0.532, P < .001).

    Cuff pressure increased during HEMS transport, demonstrating the need for routine cuff pressure monitoring during flight. Further research is required to determine if exposure to transient increases in cuff pressure for short durations is clinically significant.
    Cuff pressure increased during HEMS transport, demonstrating the need for routine cuff pressure monitoring during flight. Further research is required to determine if exposure to transient increases in cuff pressure for short durations is clinically significant.
    As part of the humanitarian response to the coronavirus disease 2019 (COVID-19) pandemic, the German and French Armed Forces provided air transport for patients from overwhelmed regional hospitals in Italy and France. The objective of this study was to analyze the characteristics of the missions and the medical conditions of COVID-19 patients transported during an air medical evacuation on fixed wing aircraft in March and April 2020.

    This was a retrospective analysis of transport records as well as other documents for 58 COVID-19 patients requiring artificial ventilation.

    The median age of the transported patients was 61.5 years, and 61% of them had preexisting medical conditions. They had been ventilated for a median of 5 days and experienced the first symptoms 18 days before transport. The patients flown out of France had less days of ventilation before flight, a lower end-tidal carbon dioxide level at the beginning of the flight, and a lower Charlson Comorbidity Index. There were also some differences between the ventilation and the flight level flown by the 2 air forces.

    The intensive care transport of ventilated COVID-19 patients requires highly qualified personnel and appropriate equipment and should be planned appropriately.
    The intensive care transport of ventilated COVID-19 patients requires highly qualified personnel and appropriate equipment and should be planned appropriately.
    Medical simulation is used in helicopter emergency services as a tool for training the crew. Using in situ simulation, we aimed to evaluate the degree of implementation, the barriers to completing simulation training, and the crew's attitude toward this form of training.

    This was a 1-year prospective study on simulation at all 14 Norwegian helicopter emergency services bases and 1 search and rescue base. Local facilitators were educated and conducted simulations at their discretion.

    All bases agreed to participate initially, but 1 opted out because of technical difficulties. The number of simulations attempted at each base ranged from 1 to 46 (median = 17). Regardless of the base and the number of attempted simulations, participating crews scored self-evaluated satisfaction with this form of training highly. Having 2 local facilitators increased the number of attempted simulations, whereas facilitators' travel distance to work seemed to make no difference on the number of attempted simulations.

    Our study reveals considerable differences in the number of attempted simulations between bases despite being given the same prerequisites. The busiest bases completed fewer simulations than the rest of the bases. Our findings suggest that conditions related to the local facilitator are important for the successful implementation of simulation-based training in helicopter emergency services.
    Our study reveals considerable differences in the number of attempted simulations between bases despite being given the same prerequisites. The busiest bases completed fewer simulations than the rest of the bases. Our findings suggest that conditions related to the local facilitator are important for the successful implementation of simulation-based training in helicopter emergency services.Laryngeal stenosis is certainly one of the most severe complications of airway intubation in children, eventually leading to tracheostomy and sometimes to additional surgical procedures. Primary prophylaxis through modification of its risk factors and secondary prophylaxis through the management of post-extubation laryngeal acute lesions seem to be key to avoidance of this fearful complication. The present article addresses known risk factors for the development of laryngeal acute lesions with emphasis on sedation level and intubation time. It also discusses available classification systems proposed in medical literature, especially the Classification of Acute Laryngeal Injuries (CALI) conceived by our research group, and its positive predictive value for the development of chronic lesions. Finally, debate focuses on treatment of each individual lesion. Despite excellent results observed with endoscopic methods for treating these lesions, there is still doubts pending over their management, and there is need for further studies to define adequate treatment for each patient and for each type of lesion.
    0%), and ventilation mode was changed for 11 patients (4.10%) during transport. The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making. The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making. The pressure within an endotracheal tube cuff is of particular importance in helicopter emergency medical services (HEMS) transport because the unpressurized cabin is subjected to decreases in atmospheric pressure. This can cause the cuff to overinflate and may be associated with clinical complications. We sought to evaluate endotracheal tube cuff pressure changes among intubated patients during HEMS transport. A prospective observational study was performed including adult patients who were intubated and transported by helicopter between April 2017 and October 2018. https://www.selleckchem.com/products/Pomalidomide(CC-4047).html Cuff pressures were measured before, during, and after HEMS transport with a commercial manometer. A total of 208 patients were included. The median maximum flight altitude was 3,000 (interquartile range [IQR], 2,000-5,000) ft. The median initial cuff pressure before takeoff was 35 (IQR, 24-50) cm H O, which increased to 50 (IQR, 35-70) cm H O at maximum altitude. A total of 169 (81.3%) patients had a cuff pressure > 30 cm H O at maximum altitude. There was a moderate correlation between altitude and cuff pressure (r = 0.532, P < .001). Cuff pressure increased during HEMS transport, demonstrating the need for routine cuff pressure monitoring during flight. Further research is required to determine if exposure to transient increases in cuff pressure for short durations is clinically significant. Cuff pressure increased during HEMS transport, demonstrating the need for routine cuff pressure monitoring during flight. Further research is required to determine if exposure to transient increases in cuff pressure for short durations is clinically significant. As part of the humanitarian response to the coronavirus disease 2019 (COVID-19) pandemic, the German and French Armed Forces provided air transport for patients from overwhelmed regional hospitals in Italy and France. The objective of this study was to analyze the characteristics of the missions and the medical conditions of COVID-19 patients transported during an air medical evacuation on fixed wing aircraft in March and April 2020. This was a retrospective analysis of transport records as well as other documents for 58 COVID-19 patients requiring artificial ventilation. The median age of the transported patients was 61.5 years, and 61% of them had preexisting medical conditions. They had been ventilated for a median of 5 days and experienced the first symptoms 18 days before transport. The patients flown out of France had less days of ventilation before flight, a lower end-tidal carbon dioxide level at the beginning of the flight, and a lower Charlson Comorbidity Index. There were also some differences between the ventilation and the flight level flown by the 2 air forces. The intensive care transport of ventilated COVID-19 patients requires highly qualified personnel and appropriate equipment and should be planned appropriately. The intensive care transport of ventilated COVID-19 patients requires highly qualified personnel and appropriate equipment and should be planned appropriately. Medical simulation is used in helicopter emergency services as a tool for training the crew. Using in situ simulation, we aimed to evaluate the degree of implementation, the barriers to completing simulation training, and the crew's attitude toward this form of training. This was a 1-year prospective study on simulation at all 14 Norwegian helicopter emergency services bases and 1 search and rescue base. Local facilitators were educated and conducted simulations at their discretion. All bases agreed to participate initially, but 1 opted out because of technical difficulties. The number of simulations attempted at each base ranged from 1 to 46 (median = 17). Regardless of the base and the number of attempted simulations, participating crews scored self-evaluated satisfaction with this form of training highly. Having 2 local facilitators increased the number of attempted simulations, whereas facilitators' travel distance to work seemed to make no difference on the number of attempted simulations. Our study reveals considerable differences in the number of attempted simulations between bases despite being given the same prerequisites. The busiest bases completed fewer simulations than the rest of the bases. Our findings suggest that conditions related to the local facilitator are important for the successful implementation of simulation-based training in helicopter emergency services. Our study reveals considerable differences in the number of attempted simulations between bases despite being given the same prerequisites. The busiest bases completed fewer simulations than the rest of the bases. Our findings suggest that conditions related to the local facilitator are important for the successful implementation of simulation-based training in helicopter emergency services.Laryngeal stenosis is certainly one of the most severe complications of airway intubation in children, eventually leading to tracheostomy and sometimes to additional surgical procedures. Primary prophylaxis through modification of its risk factors and secondary prophylaxis through the management of post-extubation laryngeal acute lesions seem to be key to avoidance of this fearful complication. The present article addresses known risk factors for the development of laryngeal acute lesions with emphasis on sedation level and intubation time. It also discusses available classification systems proposed in medical literature, especially the Classification of Acute Laryngeal Injuries (CALI) conceived by our research group, and its positive predictive value for the development of chronic lesions. Finally, debate focuses on treatment of each individual lesion. Despite excellent results observed with endoscopic methods for treating these lesions, there is still doubts pending over their management, and there is need for further studies to define adequate treatment for each patient and for each type of lesion.
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  • CD47, overexpressed on kinds of tumor cells, activates a "don't eat me" signal through binding to signal regulatory protein α (SIRPα), leading to immune escape from the mononuclear phagocyte system (MPS). It is also a huge challenge to deliver therapeutic drugs to the tumor sites due to the short retention time in blood, poor targeting of tumor cells and accelerated clearance by MPS. Herein, we designed a hybrid therapeutic nanovesicles, named as hGLV, by fusing gene-engineered exosomes with drug-loaded thermosensitive liposomes. We demonstrated that the CD47-overexpressed hGLV exhibited the long blood circulation and improved the macrophages-mediated the phagocytosis of tumor cells by blocking CD47 signal. Moreover, the resulted hGLV could remarkably target the homologous tumor in ****, achieving the preferential accumulation at the tumor sites. Importantly, hGLV loading the photothermal agent could achieve the excellent photothermal therapy (PTT) under laser irradiation after the intravenous injection, completely eliminating the tumors, leading to immunogenic cell death and generating substantial tumor-associated antigens, which could promote the maturation of immature dendritic cells with the help of the co-encapsulated immune adjuvant to trigger strong immune responses. Generally, the hybrid nanovesicles based on CD47 immune check point blockade can be a promising platform for the drug delivery in cancer treatment.It remains a great challenge for targeted therapy of heart diseases. To achieve desirable heart targeting, we developed a polyphenol-assisted nanoprecipitation/self-assembly approach for facile engineering of functional nanoparticles. Three different materials were employed as representative carriers, while gallic acid, catechin, epigallocatechin gallate, and tannic acid (TA) served as typical polyphenols with varied numbers of phenolic hydroxyl groups. By optimizing different parameters, such as polyphenol types and the weight ratio of carrier materials and polyphenols, well-defined nanoparticles with excellent physicochemical properties can be easily prepared. Regardless of various carrier materials, TA-derived nanoparticles showed potent reactive oxygen species-scavenging activity, especially nanoparticles produced from a cyclodextrin-derived bioactive material (TPCD). By internalization into cardiomyocytes, TPCD/TA nanoparticles (defined as TPTN) effectively protected cells from hypoxic-ischemic injury. After intravenous injection, TPTN considerably accumulated in the injured heart in two murine models of ventricular fibrillation cardiac arrest in rats and myocardial hypertrophy in ****. Correspondingly, intravenously delivered TPTN afforded excellent therapeutic effects in both heart diseases. Preliminary experiments also revealed good safety of TPTN. These results substantiated that TPTN is a promising nanotherapy for targeted treatment of heart diseases, while polyphenol-assisted self-assembly is a facile but robust strategy to develop heart-targeting delivery systems.Healing of large calvarial bone defects in adults adopts intramembranous pathway and is difficult. Implantation of adipose-derived stem cells (ASC) that differentiate towards chondrogenic lineage can switch the bone repair pathway and improve calvarial bone healing. Long non-coding RNA DANCR was recently uncovered to promote chondrogenesis, but its roles in rat ASC (rASC) chondrogenesis and bone healing stimulation have yet to be explored. Here we first verified that DANCR expression promoted rASC chondrogenesis, thus we harnessed CRISPR activation (CRISPRa) technology to upregulate endogenous DANCR, stimulate rASC chondrogenesis and improve calvarial bone healing in rats. We generated 4 different dCas9-VPR orthologues by fusing a tripartite transcription activator domain VPR to catalytically dead Cas9 (dCas9) derived from 4 different bacteria, and compared the degree of activation using the 4 different dCas9-VPR. We unveiled surprisingly that the most commonly used dCas9-VPR derived from Streptococcus pyogenes barely activated DANCR. Nonetheless dCas9-VPR from Staphylococcus aureus (SadCas9-VPR) triggered efficient activation of DANCR in rASC. Delivery of SadCas9-VPR and the associated guide RNA into rASC substantially enhanced chondrogenic differentiation of rASC and augmented cartilage formation in vitro. Implantation of the engineered rASC remarkably potentiated the calvarial bone healing in rats. Furthermore, we identified that DANCR improved the rASC chondrogenesis through inhibition of miR-203a and miR-214. These results collectively proved that DANCR activation by SadCas9-VPR-based CRISPRa provides a novel therapeutic approach to improving calvarial bone healing.The blood-brain barrier (BBB) tightly controls entry of molecules and cells into the brain, restricting the delivery of therapeutics. Blood-brain barrier opening (BBBO) utilizes reversible disruption of cell-cell junctions between brain microvascular endothelial cells to enable transient entry into the brain. Here, we demonstrate that melittin, a membrane active peptide present in bee venom, supports transient BBBO. From endothelial and neuronal viability studies, we first identify the accessible concentration range for BBBO. We then use a tissue-engineered model of the human BBB to optimize dosing and elucidate the mechanism of opening. Melittin and other membrane active variants transiently increase paracellular permeability via disruption of cell-cell junctions that result in transient focal leaks. To validate the results from the tissue-engineered model, we then demonstrate that transient BBBO can be reproduced in a mouse model. We identify a minimum clinically effective intra-arterial dose of 3 μM min melittin, which is reversible within one day and neurologically safe. Melittin-induced BBBO represents a novel technology for delivery of therapeutics into the brain.Nanotechnology provides a powerful tool to overcome many disadvantages of small-molecule photosensitizers for photodynamic cancer therapy, such as hydrophobicity, rapid blood clearance, low accumulation in tumor tissue and low cell penetration, etc. The occurrence of quench in photosensitizer-loaded nanoparticle greatly downregulates the ability to generate singlet oxygen with light irradiation. Stimuli-responsive nanocarriers can improve the efficacy of PDT to a certain extent. However, insufficient release of photosensitizer from either endogenous or exogenous stimuli responsive nanocarriers in the short period of light irradiation restricts full usage of the photosensitizer delivered into cancer cells. We here report a dual-step light irradiation strategy to enhance the efficacy of cancer PDT. https://www.selleckchem.com/products/bpv-hopic.html Ce6 as a photosensitizer is loaded in singlet oxygen-sensitive micelles (Ce6-M) via self-assembly of amphiphilic polymer mPEG2000-TK-C16. After co-incubation of Ce6-M with cancer cells or i.v. injection of Ce6-M, cancer cells or tumor tissues are irradiated with light for a short time to trigger Ce6 release, and 2 h later, re-irradiated for relatively long time.
    CD47, overexpressed on kinds of tumor cells, activates a "don't eat me" signal through binding to signal regulatory protein α (SIRPα), leading to immune escape from the mononuclear phagocyte system (MPS). It is also a huge challenge to deliver therapeutic drugs to the tumor sites due to the short retention time in blood, poor targeting of tumor cells and accelerated clearance by MPS. Herein, we designed a hybrid therapeutic nanovesicles, named as hGLV, by fusing gene-engineered exosomes with drug-loaded thermosensitive liposomes. We demonstrated that the CD47-overexpressed hGLV exhibited the long blood circulation and improved the macrophages-mediated the phagocytosis of tumor cells by blocking CD47 signal. Moreover, the resulted hGLV could remarkably target the homologous tumor in mice, achieving the preferential accumulation at the tumor sites. Importantly, hGLV loading the photothermal agent could achieve the excellent photothermal therapy (PTT) under laser irradiation after the intravenous injection, completely eliminating the tumors, leading to immunogenic cell death and generating substantial tumor-associated antigens, which could promote the maturation of immature dendritic cells with the help of the co-encapsulated immune adjuvant to trigger strong immune responses. Generally, the hybrid nanovesicles based on CD47 immune check point blockade can be a promising platform for the drug delivery in cancer treatment.It remains a great challenge for targeted therapy of heart diseases. To achieve desirable heart targeting, we developed a polyphenol-assisted nanoprecipitation/self-assembly approach for facile engineering of functional nanoparticles. Three different materials were employed as representative carriers, while gallic acid, catechin, epigallocatechin gallate, and tannic acid (TA) served as typical polyphenols with varied numbers of phenolic hydroxyl groups. By optimizing different parameters, such as polyphenol types and the weight ratio of carrier materials and polyphenols, well-defined nanoparticles with excellent physicochemical properties can be easily prepared. Regardless of various carrier materials, TA-derived nanoparticles showed potent reactive oxygen species-scavenging activity, especially nanoparticles produced from a cyclodextrin-derived bioactive material (TPCD). By internalization into cardiomyocytes, TPCD/TA nanoparticles (defined as TPTN) effectively protected cells from hypoxic-ischemic injury. After intravenous injection, TPTN considerably accumulated in the injured heart in two murine models of ventricular fibrillation cardiac arrest in rats and myocardial hypertrophy in mice. Correspondingly, intravenously delivered TPTN afforded excellent therapeutic effects in both heart diseases. Preliminary experiments also revealed good safety of TPTN. These results substantiated that TPTN is a promising nanotherapy for targeted treatment of heart diseases, while polyphenol-assisted self-assembly is a facile but robust strategy to develop heart-targeting delivery systems.Healing of large calvarial bone defects in adults adopts intramembranous pathway and is difficult. Implantation of adipose-derived stem cells (ASC) that differentiate towards chondrogenic lineage can switch the bone repair pathway and improve calvarial bone healing. Long non-coding RNA DANCR was recently uncovered to promote chondrogenesis, but its roles in rat ASC (rASC) chondrogenesis and bone healing stimulation have yet to be explored. Here we first verified that DANCR expression promoted rASC chondrogenesis, thus we harnessed CRISPR activation (CRISPRa) technology to upregulate endogenous DANCR, stimulate rASC chondrogenesis and improve calvarial bone healing in rats. We generated 4 different dCas9-VPR orthologues by fusing a tripartite transcription activator domain VPR to catalytically dead Cas9 (dCas9) derived from 4 different bacteria, and compared the degree of activation using the 4 different dCas9-VPR. We unveiled surprisingly that the most commonly used dCas9-VPR derived from Streptococcus pyogenes barely activated DANCR. Nonetheless dCas9-VPR from Staphylococcus aureus (SadCas9-VPR) triggered efficient activation of DANCR in rASC. Delivery of SadCas9-VPR and the associated guide RNA into rASC substantially enhanced chondrogenic differentiation of rASC and augmented cartilage formation in vitro. Implantation of the engineered rASC remarkably potentiated the calvarial bone healing in rats. Furthermore, we identified that DANCR improved the rASC chondrogenesis through inhibition of miR-203a and miR-214. These results collectively proved that DANCR activation by SadCas9-VPR-based CRISPRa provides a novel therapeutic approach to improving calvarial bone healing.The blood-brain barrier (BBB) tightly controls entry of molecules and cells into the brain, restricting the delivery of therapeutics. Blood-brain barrier opening (BBBO) utilizes reversible disruption of cell-cell junctions between brain microvascular endothelial cells to enable transient entry into the brain. Here, we demonstrate that melittin, a membrane active peptide present in bee venom, supports transient BBBO. From endothelial and neuronal viability studies, we first identify the accessible concentration range for BBBO. We then use a tissue-engineered model of the human BBB to optimize dosing and elucidate the mechanism of opening. Melittin and other membrane active variants transiently increase paracellular permeability via disruption of cell-cell junctions that result in transient focal leaks. To validate the results from the tissue-engineered model, we then demonstrate that transient BBBO can be reproduced in a mouse model. We identify a minimum clinically effective intra-arterial dose of 3 μM min melittin, which is reversible within one day and neurologically safe. Melittin-induced BBBO represents a novel technology for delivery of therapeutics into the brain.Nanotechnology provides a powerful tool to overcome many disadvantages of small-molecule photosensitizers for photodynamic cancer therapy, such as hydrophobicity, rapid blood clearance, low accumulation in tumor tissue and low cell penetration, etc. The occurrence of quench in photosensitizer-loaded nanoparticle greatly downregulates the ability to generate singlet oxygen with light irradiation. Stimuli-responsive nanocarriers can improve the efficacy of PDT to a certain extent. However, insufficient release of photosensitizer from either endogenous or exogenous stimuli responsive nanocarriers in the short period of light irradiation restricts full usage of the photosensitizer delivered into cancer cells. We here report a dual-step light irradiation strategy to enhance the efficacy of cancer PDT. https://www.selleckchem.com/products/bpv-hopic.html Ce6 as a photosensitizer is loaded in singlet oxygen-sensitive micelles (Ce6-M) via self-assembly of amphiphilic polymer mPEG2000-TK-C16. After co-incubation of Ce6-M with cancer cells or i.v. injection of Ce6-M, cancer cells or tumor tissues are irradiated with light for a short time to trigger Ce6 release, and 2 h later, re-irradiated for relatively long time.
    0 التعليقات 0 المشاركات 117 مشاهدة 0 معاينة

  • Many researchers from scientific and industrial fields have devoted their efforts to the laser interferometer, aiming to improve the measurement accuracy and extend the practical applications. Here, we present a modified homodyne laser interferometer based on phase modulation for simultaneously measuring displacement and angle. The active sawtooth wave phase modulation enhances immunity of this interferometer to the environmental fluctuations and laser power drift. Based on polarized optic theory and the sinusoidal measurement retro-reflector, a modified Michelson-type interferometer configuration is designed to simultaneously measure displacement and angle. Phase difference between the reference and measurement interference signals can be obtained using the sawtooth wave phase modulation and zero crossing detection technique, where the real-time displacement and angle values can be derived directly. Experimental results demonstrate our proposed interferometer has good static and dynamic performance.Quantitative phase imaging using holographic microscopy is a powerful and non-invasive imaging method, ideal for studying cells and quantifying their features such as size, thickness, and dry mass. However, biological materials scatter little light, and the resulting low signal-to-noise ratio in holograms complicates any downstream feature extraction and hence applications. More specifically, unwrapping phase maps from noisy holograms often fails or requires extensive computational resources. We present a strategy for overcoming the noise limitation rather than a traditional phase-unwrapping method, we extract the continuous phase values from holograms by using a phase-generation technique based on conditional generative adversarial networks employing a Pix2Pix architecture. We demonstrate that a network trained on random surfaces can accurately generate phase maps for test objects such as dumbbells, spheres, and biconcave discoids. Furthermore, we show that even a rapidly trained network can generate faithful phase maps when trained on related objects. We are able to accurately extract both morphological and quantitative features from the noisy phase maps of human leukemia (HL-60) cells, where traditional phase unwrapping algorithms fail. We conclude that deep learning can decouple noise from signal, expanding potential applications to real-world systems that may be noisy.A spectral polarization camera based on ghost imaging via sparsity constraints (GISC) is presented. The proposed imager modulates three-dimensional spatial and spectral information of the target into two-dimensional speckle patterns using a spatial random phase modulator and then acquires the speckle patterns at four linear polarization channels through a polarized CCD. The experimental results verify the feasibility of the system structure and reconstruction algorithm. The GISC spectral polarization camera, which has a simple structure and achieves compressive sampling during the imaging acquisition process, provides a simple scheme for obtaining multi-dimensional information of the light field.Conducting research using micrometer-sized X-ray beams with small samples is common at modern synchrotron X-ray sources. Often, the relative alignment between the X-ray beam and sample is time consuming. https://www.selleckchem.com/products/jg98.html An on-axis or coaxial camera system with a view of the sample in a direction along the path of the X-ray beam with its depth of field set to coincide with the location of the focal spot of the X-ray beam is preferred. Besides the use of a drilled mirror, I propose the use of a Pellicle mirror to create an on-axis viewer that allows various sample environments and X-ray beam sizes.A photonic scheme that can simultaneously estimate the microwave Doppler-frequency shift (DFS) and angle-of-arrive (AOA) is demonstrated. In the proposed system, the transmitted signal is independently mixed with two echo signals by a dual-channel microwave photonic mixer. By measuring the frequency of the intermediate frequency (IF) signal output from the two channels and the phase difference between them, the DFS (with direction identification) and AOA parameters can be obtained. In a proof-of-concept experiment, the errors are less than $\pm\;0.08\;\rmHz$ for the DFS measurement within a range of $\rm\pm 100\;\rmkHz$ and less than $\rm\pm 1.3\deg$ for the AOA measurement ranging from 0° to 90°, respectively.We report a detailed experimental and theoretical analysis of the $^4\rm F_9/2$ to $^6\rm H_13/2$ lasing transition of a dysprosium ($\rm Dy^3 +$)-doped ZBLAN fiber, a strong candidate for future compact and highly efficient yellow laser emission. Experimentally, we used a gallium nitride laser diode emitting at 447 nm as a pump source and measured yellow laser output generated with a maximum slope efficiency of 33%, which is less than half of the Stokes limit (of $\sim78\%$). This result is commensurate with two other reports of yellow emission from $\rm Dy^3 +$. As a result, we developed a numerical model to understand and analyze the improvement potential of this fiber laser system. For reliable spectroscopic data input to the numerical model, we measured the absorption and emission cross sections from $\rm Dy^3 +$-doped ZBLAN glass. We investigated the potential causes of the low experimental slope efficiency and found contributions from the background loss of the fiber and excited-state absorption (ESA) of the intracavity yellow light. We estimated the signal re-absorption cross section using the emission cross section and the McCumber relation, which was subsequently used in our numerical model to compare successfully with our experimental results. We show that the ESA can be reduced for future $\rm Dy^3 +$-doped yellow laser systems by cascade lasing or co-doping with a suitable rare earth ion desensitizer.For the current problems of extremely complex visible light indoor positioning algorithms and devices and low positioning accuracy, this paper proposes an improved indoor positioning method combining light-emitting diode (LED) visible light and quick response (QR) codes. First, initial positioning is achieved by loading a QR code image containing LED position information on the LED light, which is recognized and decoded by the receiver. Then the position of the receiver is precisely located by proposing an improved indoor positioning method. The experiment shows the smallest average error of 4.0326 cm in positioning, which greatly improves the indoor positioning accuracy.
    Many researchers from scientific and industrial fields have devoted their efforts to the laser interferometer, aiming to improve the measurement accuracy and extend the practical applications. Here, we present a modified homodyne laser interferometer based on phase modulation for simultaneously measuring displacement and angle. The active sawtooth wave phase modulation enhances immunity of this interferometer to the environmental fluctuations and laser power drift. Based on polarized optic theory and the sinusoidal measurement retro-reflector, a modified Michelson-type interferometer configuration is designed to simultaneously measure displacement and angle. Phase difference between the reference and measurement interference signals can be obtained using the sawtooth wave phase modulation and zero crossing detection technique, where the real-time displacement and angle values can be derived directly. Experimental results demonstrate our proposed interferometer has good static and dynamic performance.Quantitative phase imaging using holographic microscopy is a powerful and non-invasive imaging method, ideal for studying cells and quantifying their features such as size, thickness, and dry mass. However, biological materials scatter little light, and the resulting low signal-to-noise ratio in holograms complicates any downstream feature extraction and hence applications. More specifically, unwrapping phase maps from noisy holograms often fails or requires extensive computational resources. We present a strategy for overcoming the noise limitation rather than a traditional phase-unwrapping method, we extract the continuous phase values from holograms by using a phase-generation technique based on conditional generative adversarial networks employing a Pix2Pix architecture. We demonstrate that a network trained on random surfaces can accurately generate phase maps for test objects such as dumbbells, spheres, and biconcave discoids. Furthermore, we show that even a rapidly trained network can generate faithful phase maps when trained on related objects. We are able to accurately extract both morphological and quantitative features from the noisy phase maps of human leukemia (HL-60) cells, where traditional phase unwrapping algorithms fail. We conclude that deep learning can decouple noise from signal, expanding potential applications to real-world systems that may be noisy.A spectral polarization camera based on ghost imaging via sparsity constraints (GISC) is presented. The proposed imager modulates three-dimensional spatial and spectral information of the target into two-dimensional speckle patterns using a spatial random phase modulator and then acquires the speckle patterns at four linear polarization channels through a polarized CCD. The experimental results verify the feasibility of the system structure and reconstruction algorithm. The GISC spectral polarization camera, which has a simple structure and achieves compressive sampling during the imaging acquisition process, provides a simple scheme for obtaining multi-dimensional information of the light field.Conducting research using micrometer-sized X-ray beams with small samples is common at modern synchrotron X-ray sources. Often, the relative alignment between the X-ray beam and sample is time consuming. https://www.selleckchem.com/products/jg98.html An on-axis or coaxial camera system with a view of the sample in a direction along the path of the X-ray beam with its depth of field set to coincide with the location of the focal spot of the X-ray beam is preferred. Besides the use of a drilled mirror, I propose the use of a Pellicle mirror to create an on-axis viewer that allows various sample environments and X-ray beam sizes.A photonic scheme that can simultaneously estimate the microwave Doppler-frequency shift (DFS) and angle-of-arrive (AOA) is demonstrated. In the proposed system, the transmitted signal is independently mixed with two echo signals by a dual-channel microwave photonic mixer. By measuring the frequency of the intermediate frequency (IF) signal output from the two channels and the phase difference between them, the DFS (with direction identification) and AOA parameters can be obtained. In a proof-of-concept experiment, the errors are less than $\pm\;0.08\;\rmHz$ for the DFS measurement within a range of $\rm\pm 100\;\rmkHz$ and less than $\rm\pm 1.3\deg$ for the AOA measurement ranging from 0° to 90°, respectively.We report a detailed experimental and theoretical analysis of the $^4\rm F_9/2$ to $^6\rm H_13/2$ lasing transition of a dysprosium ($\rm Dy^3 +$)-doped ZBLAN fiber, a strong candidate for future compact and highly efficient yellow laser emission. Experimentally, we used a gallium nitride laser diode emitting at 447 nm as a pump source and measured yellow laser output generated with a maximum slope efficiency of 33%, which is less than half of the Stokes limit (of $\sim78\%$). This result is commensurate with two other reports of yellow emission from $\rm Dy^3 +$. As a result, we developed a numerical model to understand and analyze the improvement potential of this fiber laser system. For reliable spectroscopic data input to the numerical model, we measured the absorption and emission cross sections from $\rm Dy^3 +$-doped ZBLAN glass. We investigated the potential causes of the low experimental slope efficiency and found contributions from the background loss of the fiber and excited-state absorption (ESA) of the intracavity yellow light. We estimated the signal re-absorption cross section using the emission cross section and the McCumber relation, which was subsequently used in our numerical model to compare successfully with our experimental results. We show that the ESA can be reduced for future $\rm Dy^3 +$-doped yellow laser systems by cascade lasing or co-doping with a suitable rare earth ion desensitizer.For the current problems of extremely complex visible light indoor positioning algorithms and devices and low positioning accuracy, this paper proposes an improved indoor positioning method combining light-emitting diode (LED) visible light and quick response (QR) codes. First, initial positioning is achieved by loading a QR code image containing LED position information on the LED light, which is recognized and decoded by the receiver. Then the position of the receiver is precisely located by proposing an improved indoor positioning method. The experiment shows the smallest average error of 4.0326 cm in positioning, which greatly improves the indoor positioning accuracy.
    0 التعليقات 0 المشاركات 135 مشاهدة 0 معاينة

  • Members of the transient receptor potential (TRP) channels that are expressed in the kidney have gained prominence in recent years following discoveries of their role in maintaining the integrity of the filtration barrier, regulating tubular reabsorption of Ca2+ and Mg2+, and sensing osmotic stimuli. Furthermore, evidence has linked mutations in TRP channels to kidney disease pathophysiological mechanisms, including focal segmental glomerulosclerosis, disturbances in Mg2+ homeostasis, and polycystic kidney disease. Several subtypes of TRP channels are expressed in the renal vasculature, from preglomerular arteries and arterioles to the descending vasa recta. Although investigations on the physiological and pathological significance of renal vascular TRP channels are sparse, studies on isolated vessels and cells have suggested their involvement in renal vasoregulation. Renal blood flow (RBF) is an essential determinant of kidney function, including glomerular filtration, water and solute reabsorption, and waste product excretion. Functional alterations in ion channels that are expressed in the endothelium and smooth muscle of renal vessels can modulate renal vascular resistance, arterial pressure, and RBF. Hence, renal vascular TRP channels are potential therapeutic targets for the treatment of kidney disease. This review summarizes the current knowledge of TRP channel expression in renal vasculature and their role in controlling kidney function in health and disease.
    Tai Chi (TC) has shown beneficial effects on joint function in knee osteoarthritis (OA). Biomechanical mechanisms of knee joint contact load (JCL) and muscle activations during TC are less understood. The purpose of this biomechanical simulation study was to examine JCL of TC gait, the most common used TC from and its causal interactions with muscle activations in knee OA.

    Six knee OA and five healthy participants were recruited. Their full body motion of TC gait was collected. The JCL and muscle forces were quantified using a musculoskeletal simulation approach based on collected kinematics and kinetics. The JCL and muscle activations were compared between knee OA and healthy control group. In addition, the muscle contributions to the JCL were determined and compared between the two groups.

    Knee OA subjects had lower peak anterior-posterior shear forces and higher lateral shear forces than healthy control subjects during TC gait. Knee OA subjects also showed higher activations of knee flexor muscles than control subjects. Both knee extensor and flexors of the knee OA group were contributing to JCL and in the control group mainly the knee extensors.

    Our simulation results showed the JCL, muscle forces profiles, and muscle contributions to the JCL during TC gait in knee OA. https://www.selleckchem.com/products/ON-01910.html The findings of this study provided a direct scientific link between JCL and muscle forces during TC gait in knee OA. This would allow us to develop more effective TC interventions for knee OA in the future.
    Our simulation results showed the JCL, muscle forces profiles, and muscle contributions to the JCL during TC gait in knee OA. The findings of this study provided a direct scientific link between JCL and muscle forces during TC gait in knee OA. This would allow us to develop more effective TC interventions for knee OA in the future.Coronary artery disease (***) is the commonest type of heart disease and over 80% of the deaths resulted from the diseases occurred in developing countries including Nigeria, with majority being in those victims are below 70 years of age. Though, *** is not a well known disease in Nigeria but however in year 2014, 2.82% of the total of deaths occurred in the country were due to the disease. In this study, a machine leaning predictive models for *** has been developed with diagnostic *** dataset obtained in the two General Hospitals in Kano State-Nigeria. The dataset applied on machine learning algorithms which include support vector machine, K nearest neighbor, random tree, Naïve Bayes, gradient boosting and logistic regression algorithms to build the predictive models and the models were evaluated based accuracy, specificity, sensitivity and receiver operating curve (ROC) performance evaluation techniques. In terms of accuracy random forest-based machine learning model emerged to be the best model with 92.04%, for specificity Naive Bayes based machine learning model emerged to be the best model with 92.40%, while for sensitivity support vector machine based machine learning model emerged to be the best model with 87.34% and for ROC, random forest-based machine learning model emerged to be the best model with 92.20%. The decision tree generated with random forest machine learning algorithm which happened to be best model in terms accuracy and ROC can be converted into production rules and be used develop expert system for diagnosis of *** patients in Nigeria.With the world facing the new virus SARS-CoV-2, many countries have introduced instant Internet applications to identify people carrying the infection. Internet-of-Medical-Things (IoMT) have proven useful in collecting medical data as well in tracing an individual carrying the virus. The data collected or traced belongs to an individual and should be revealed to themselves and hospital providers, but not to any third-party unauthorized agencies. In this paper we use an off-chain distributed storage solution for loading large medical data sets and a blockchain implementation to securely transfer the data from the infected person to the hospital system using the edge infrastructure, and call it CoviChain. The Coronavirus Disease (COVID-19) statistics are loaded on to the edge, and moved to InterPlanetary File Systems (IPFS) storage to retrieve the hash of the data file. Once the hash is obtained, it is moved to the blockchain by means of smart contracts. As the information is being hashed twice, CoviChain addresses the security and privacy issues and avoid exposing individuals' data while achieving larger data storage on the blockchain with reduced cost and time.DNA polymerase theta (POLθ) is synthetic lethal with Homologous Recombination (HR) deficiency and thus a candidate target for HR-deficient cancers. Through high-throughput small molecule screens we identified the antibiotic Novobiocin (NVB) as a specific POLθ inhibitor that selectively kills HR-deficient tumor cells in vitro and in vivo. NVB directly binds to the POLθ ATPase domain, inhibits its ATPase activity, and phenocopies POLθ depletion. NVB kills HR-deficient breast and ovarian tumors in GEMM, xenograft and PDX models. Increased POLθ levels predict NVB sensitivity, and ****-deficient tumor cells with acquired resistance to PARP inhibitors (PARPi) are sensitive to NVB in vitro and in vivo. Mechanistically, NVB-mediated cell death in PARPi-resistant cells arises from increased double-strand break end resection, leading to accumulation of single-strand DNA intermediates and non-functional RAD51 foci. Our results demonstrate that NVB may be useful alone or in combination with PARPi in treating HR-deficient tumors, including those with acquired PARPi resistance.
    Members of the transient receptor potential (TRP) channels that are expressed in the kidney have gained prominence in recent years following discoveries of their role in maintaining the integrity of the filtration barrier, regulating tubular reabsorption of Ca2+ and Mg2+, and sensing osmotic stimuli. Furthermore, evidence has linked mutations in TRP channels to kidney disease pathophysiological mechanisms, including focal segmental glomerulosclerosis, disturbances in Mg2+ homeostasis, and polycystic kidney disease. Several subtypes of TRP channels are expressed in the renal vasculature, from preglomerular arteries and arterioles to the descending vasa recta. Although investigations on the physiological and pathological significance of renal vascular TRP channels are sparse, studies on isolated vessels and cells have suggested their involvement in renal vasoregulation. Renal blood flow (RBF) is an essential determinant of kidney function, including glomerular filtration, water and solute reabsorption, and waste product excretion. Functional alterations in ion channels that are expressed in the endothelium and smooth muscle of renal vessels can modulate renal vascular resistance, arterial pressure, and RBF. Hence, renal vascular TRP channels are potential therapeutic targets for the treatment of kidney disease. This review summarizes the current knowledge of TRP channel expression in renal vasculature and their role in controlling kidney function in health and disease. Tai Chi (TC) has shown beneficial effects on joint function in knee osteoarthritis (OA). Biomechanical mechanisms of knee joint contact load (JCL) and muscle activations during TC are less understood. The purpose of this biomechanical simulation study was to examine JCL of TC gait, the most common used TC from and its causal interactions with muscle activations in knee OA. Six knee OA and five healthy participants were recruited. Their full body motion of TC gait was collected. The JCL and muscle forces were quantified using a musculoskeletal simulation approach based on collected kinematics and kinetics. The JCL and muscle activations were compared between knee OA and healthy control group. In addition, the muscle contributions to the JCL were determined and compared between the two groups. Knee OA subjects had lower peak anterior-posterior shear forces and higher lateral shear forces than healthy control subjects during TC gait. Knee OA subjects also showed higher activations of knee flexor muscles than control subjects. Both knee extensor and flexors of the knee OA group were contributing to JCL and in the control group mainly the knee extensors. Our simulation results showed the JCL, muscle forces profiles, and muscle contributions to the JCL during TC gait in knee OA. https://www.selleckchem.com/products/ON-01910.html The findings of this study provided a direct scientific link between JCL and muscle forces during TC gait in knee OA. This would allow us to develop more effective TC interventions for knee OA in the future. Our simulation results showed the JCL, muscle forces profiles, and muscle contributions to the JCL during TC gait in knee OA. The findings of this study provided a direct scientific link between JCL and muscle forces during TC gait in knee OA. This would allow us to develop more effective TC interventions for knee OA in the future.Coronary artery disease (CAD) is the commonest type of heart disease and over 80% of the deaths resulted from the diseases occurred in developing countries including Nigeria, with majority being in those victims are below 70 years of age. Though, CAD is not a well known disease in Nigeria but however in year 2014, 2.82% of the total of deaths occurred in the country were due to the disease. In this study, a machine leaning predictive models for CAD has been developed with diagnostic CAD dataset obtained in the two General Hospitals in Kano State-Nigeria. The dataset applied on machine learning algorithms which include support vector machine, K nearest neighbor, random tree, Naïve Bayes, gradient boosting and logistic regression algorithms to build the predictive models and the models were evaluated based accuracy, specificity, sensitivity and receiver operating curve (ROC) performance evaluation techniques. In terms of accuracy random forest-based machine learning model emerged to be the best model with 92.04%, for specificity Naive Bayes based machine learning model emerged to be the best model with 92.40%, while for sensitivity support vector machine based machine learning model emerged to be the best model with 87.34% and for ROC, random forest-based machine learning model emerged to be the best model with 92.20%. The decision tree generated with random forest machine learning algorithm which happened to be best model in terms accuracy and ROC can be converted into production rules and be used develop expert system for diagnosis of CAD patients in Nigeria.With the world facing the new virus SARS-CoV-2, many countries have introduced instant Internet applications to identify people carrying the infection. Internet-of-Medical-Things (IoMT) have proven useful in collecting medical data as well in tracing an individual carrying the virus. The data collected or traced belongs to an individual and should be revealed to themselves and hospital providers, but not to any third-party unauthorized agencies. In this paper we use an off-chain distributed storage solution for loading large medical data sets and a blockchain implementation to securely transfer the data from the infected person to the hospital system using the edge infrastructure, and call it CoviChain. The Coronavirus Disease (COVID-19) statistics are loaded on to the edge, and moved to InterPlanetary File Systems (IPFS) storage to retrieve the hash of the data file. Once the hash is obtained, it is moved to the blockchain by means of smart contracts. As the information is being hashed twice, CoviChain addresses the security and privacy issues and avoid exposing individuals' data while achieving larger data storage on the blockchain with reduced cost and time.DNA polymerase theta (POLθ) is synthetic lethal with Homologous Recombination (HR) deficiency and thus a candidate target for HR-deficient cancers. Through high-throughput small molecule screens we identified the antibiotic Novobiocin (NVB) as a specific POLθ inhibitor that selectively kills HR-deficient tumor cells in vitro and in vivo. NVB directly binds to the POLθ ATPase domain, inhibits its ATPase activity, and phenocopies POLθ depletion. NVB kills HR-deficient breast and ovarian tumors in GEMM, xenograft and PDX models. Increased POLθ levels predict NVB sensitivity, and BRCA-deficient tumor cells with acquired resistance to PARP inhibitors (PARPi) are sensitive to NVB in vitro and in vivo. Mechanistically, NVB-mediated cell death in PARPi-resistant cells arises from increased double-strand break end resection, leading to accumulation of single-strand DNA intermediates and non-functional RAD51 foci. Our results demonstrate that NVB may be useful alone or in combination with PARPi in treating HR-deficient tumors, including those with acquired PARPi resistance.
    0 التعليقات 0 المشاركات 49 مشاهدة 0 معاينة

  • Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.The usage of 3D-printing for drug-eluting implants combines the advantages of a targeted local drug therapy over longer periods of time at the precise location of the disease with a manufacturing technique that easily allows modifications of the implant shape to comply with the individual needs of each patient. Research until now has been focused on several aspects of this topic such as 3D-printing with different materials or printing techniques to achieve implants with different shapes, mechanical properties or release profiles. This review is intended to provide an overview of the developments currently described in the literature. The topic is very multifaceted and several of the investigated aspects are not related to just one type of application. Consequently, this overview deals with the topic of 3D-printed drug-eluting implants in the application fields of stents and catheters, gynecological devices, devices for bone treatment and surgical screws, antitumoral devices and surgical meshes, as well as other devices with either simple or complex geometry. Overall, the current findings highlight the great potential of the manufacturing of drug-eluting implants via 3D-printing technology for advanced individualized medicine despite remaining challenges such as the regulatory approval of individualized implants.Herein, we present the synthesis and crystal structures determination of five 4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenol derivatives containing halogen atoms, 6a-e, which may be used as an excellent mimic of steroids in the drug development process. Good quality crystals obtained for all of the synthesized compounds allowed the analysis of their molecular structures. Subsequently, the determined crystal structures were used to calculate the Hirshfeld surfaces for each of the synthesized compounds. Furthermore, results of our docking studies indicated that synthesized derivatives are able to bind effectively to the active sites of selected enzymes and receptors involved in the hormone biosynthesis and signaling pathways, analogously to the native steroids.A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host-guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L-α-amino acid esters (all cryptochiral molecules) tested as possible guests. The host-guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. https://www.selleckchem.com/products/SB-202190.html This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host-guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.Pincer complexes play an important role in organometallic chemistry; in particular, their use as homogeneous catalysts for organic transformations has increased dramatically in recent years. The high catalytic activity of such bis-cyclometallic complexes is associated with the easy tunability of their properties. Moreover, the phosphorus-based unsymmetrical pincers showed higher catalytic activity than the corresponding symmetrical analogues in several catalytic reactions. However, in modern literature, an increasing interest in the development of catalysts based on non-precious metals is observed. For example, nickel, which is an affordable and sustainable analogue of platinum and palladium, known for its low toxicity, has attracted increasing attention in the catalytic chemistry of transition metals in recent years. Thus, this mini-review is devoted to the recent advances in the chemistry of unsymmetrical phosphorus-based pincer nickel complexes, including the ligand design, the synthesis of nickel complexes and their catalytic applications.The membrane is a crucial component of Zn slurry-air flow battery since it provides ionic conductivity between the electrodes while avoiding the mixing of the two compartments. Herein, six commercial membranes (Cellophane™ 350PØØ, Zirfon®, Fumatech® PBI, Celgard® 3501, 3401 and 5550) were first characterized in terms of electrolyte uptake, ion conductivity and zincate ion crossover, and tested in Zn slurry-air flow battery. The peak power density of the battery employing the membranes was found to depend on the in-situ cell resistance. Among them, the cell using Celgard® 3501 membrane, with in-situ area resistance of 2 Ω cm2 at room temperature displayed the highest peak power density (90 mW cm-2). However, due to the porous nature of most of these membranes, a significant crossover of zincate ions was observed. To address this issue, an ion-selective ionomer containing modified poly(phenylene oxide) (PPO) and N-spirocyclic quaternary ammonium monomer was coated on a Celgard® 3501 membrane and crosslinked via UV irradiation (PPO-3.
    Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.The usage of 3D-printing for drug-eluting implants combines the advantages of a targeted local drug therapy over longer periods of time at the precise location of the disease with a manufacturing technique that easily allows modifications of the implant shape to comply with the individual needs of each patient. Research until now has been focused on several aspects of this topic such as 3D-printing with different materials or printing techniques to achieve implants with different shapes, mechanical properties or release profiles. This review is intended to provide an overview of the developments currently described in the literature. The topic is very multifaceted and several of the investigated aspects are not related to just one type of application. Consequently, this overview deals with the topic of 3D-printed drug-eluting implants in the application fields of stents and catheters, gynecological devices, devices for bone treatment and surgical screws, antitumoral devices and surgical meshes, as well as other devices with either simple or complex geometry. Overall, the current findings highlight the great potential of the manufacturing of drug-eluting implants via 3D-printing technology for advanced individualized medicine despite remaining challenges such as the regulatory approval of individualized implants.Herein, we present the synthesis and crystal structures determination of five 4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenol derivatives containing halogen atoms, 6a-e, which may be used as an excellent mimic of steroids in the drug development process. Good quality crystals obtained for all of the synthesized compounds allowed the analysis of their molecular structures. Subsequently, the determined crystal structures were used to calculate the Hirshfeld surfaces for each of the synthesized compounds. Furthermore, results of our docking studies indicated that synthesized derivatives are able to bind effectively to the active sites of selected enzymes and receptors involved in the hormone biosynthesis and signaling pathways, analogously to the native steroids.A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host-guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L-α-amino acid esters (all cryptochiral molecules) tested as possible guests. The host-guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. https://www.selleckchem.com/products/SB-202190.html This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host-guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.Pincer complexes play an important role in organometallic chemistry; in particular, their use as homogeneous catalysts for organic transformations has increased dramatically in recent years. The high catalytic activity of such bis-cyclometallic complexes is associated with the easy tunability of their properties. Moreover, the phosphorus-based unsymmetrical pincers showed higher catalytic activity than the corresponding symmetrical analogues in several catalytic reactions. However, in modern literature, an increasing interest in the development of catalysts based on non-precious metals is observed. For example, nickel, which is an affordable and sustainable analogue of platinum and palladium, known for its low toxicity, has attracted increasing attention in the catalytic chemistry of transition metals in recent years. Thus, this mini-review is devoted to the recent advances in the chemistry of unsymmetrical phosphorus-based pincer nickel complexes, including the ligand design, the synthesis of nickel complexes and their catalytic applications.The membrane is a crucial component of Zn slurry-air flow battery since it provides ionic conductivity between the electrodes while avoiding the mixing of the two compartments. Herein, six commercial membranes (Cellophane™ 350PØØ, Zirfon®, Fumatech® PBI, Celgard® 3501, 3401 and 5550) were first characterized in terms of electrolyte uptake, ion conductivity and zincate ion crossover, and tested in Zn slurry-air flow battery. The peak power density of the battery employing the membranes was found to depend on the in-situ cell resistance. Among them, the cell using Celgard® 3501 membrane, with in-situ area resistance of 2 Ω cm2 at room temperature displayed the highest peak power density (90 mW cm-2). However, due to the porous nature of most of these membranes, a significant crossover of zincate ions was observed. To address this issue, an ion-selective ionomer containing modified poly(phenylene oxide) (PPO) and N-spirocyclic quaternary ammonium monomer was coated on a Celgard® 3501 membrane and crosslinked via UV irradiation (PPO-3.
    0 التعليقات 0 المشاركات 33 مشاهدة 0 معاينة

  • Interaction effects between the 2.856 and 1.5 GHz microwaves were found in the EEG and p-CREB changes. Our findings indicated that 2.856 GHz and 1.5 GHz microwave exposure induced a decline in spatial memory, which might be related to p-AKT, p-CaMK II, p-CREB and p-ERK1/2.Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC. We used RNA-sequencing and computational techniques to compare gene expression patterns in human fetal/infant livers, adult liver, and iHLC. We identified distinct gene expression profiles between the human feta/infant livers compared to adult liver, and close resemblance of iHLC to human developing livers. Compared to adult, both developing livers and iHLC had significant downregulation of xenobiotic, bile acid, and fatty acid metabolism; and lower expression of the sterol metabolizing gene ABCG8. When challenged with stigmasterol, a plant sterol found in intravenous soy lipids, lipid accumulation was significantly higher in iHLC compared to adult-derived HepG2 cells. Our findings provide insights into altered bile acid and lipid metabolizing processes in the immature human liver, and support the use of iHLC as a relevant model system of developing liver to study lipid metabolism and PNAC.Metabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2-/- murine macrophages. In vivo, the impact of AMPK and Parkin was determined in **** subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. **** were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient ****/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed ****. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. https://www.selleckchem.com/products/mptp-hydrochloride.html AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.In this paper, a new powerful deep learning framework, named as DENTECT, is developed in order to instantly detect five different dental treatment approaches and simultaneously number the dentition based on the FDI notation on panoramic X-ray images. This makes DENTECT the first system that focuses on identification of multiple dental treatments; namely periapical lesion therapy, fillings, root canal treatment (RCT), surgical extraction, and conventional extraction all of which are accurately located within their corresponding borders and tooth numbers. Although DENTECT is trained on only 1005 images, the annotations supplied by experts provide satisfactory results for both treatment and enumeration detection. This framework carries out enumeration with an average precision (AP) score of 89.4% and performs treatment identification with a 59.0% AP score. Clinically, DENTECT is a practical and adoptable tool that accelerates the process of treatment planning with a level of accuracy which could compete with that of dental clinicians.Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P  less then  0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P  less then  0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P  less then  0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.
    Interaction effects between the 2.856 and 1.5 GHz microwaves were found in the EEG and p-CREB changes. Our findings indicated that 2.856 GHz and 1.5 GHz microwave exposure induced a decline in spatial memory, which might be related to p-AKT, p-CaMK II, p-CREB and p-ERK1/2.Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC. We used RNA-sequencing and computational techniques to compare gene expression patterns in human fetal/infant livers, adult liver, and iHLC. We identified distinct gene expression profiles between the human feta/infant livers compared to adult liver, and close resemblance of iHLC to human developing livers. Compared to adult, both developing livers and iHLC had significant downregulation of xenobiotic, bile acid, and fatty acid metabolism; and lower expression of the sterol metabolizing gene ABCG8. When challenged with stigmasterol, a plant sterol found in intravenous soy lipids, lipid accumulation was significantly higher in iHLC compared to adult-derived HepG2 cells. Our findings provide insights into altered bile acid and lipid metabolizing processes in the immature human liver, and support the use of iHLC as a relevant model system of developing liver to study lipid metabolism and PNAC.Metabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2-/- murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. https://www.selleckchem.com/products/mptp-hydrochloride.html AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.In this paper, a new powerful deep learning framework, named as DENTECT, is developed in order to instantly detect five different dental treatment approaches and simultaneously number the dentition based on the FDI notation on panoramic X-ray images. This makes DENTECT the first system that focuses on identification of multiple dental treatments; namely periapical lesion therapy, fillings, root canal treatment (RCT), surgical extraction, and conventional extraction all of which are accurately located within their corresponding borders and tooth numbers. Although DENTECT is trained on only 1005 images, the annotations supplied by experts provide satisfactory results for both treatment and enumeration detection. This framework carries out enumeration with an average precision (AP) score of 89.4% and performs treatment identification with a 59.0% AP score. Clinically, DENTECT is a practical and adoptable tool that accelerates the process of treatment planning with a level of accuracy which could compete with that of dental clinicians.Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P  less then  0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P  less then  0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P  less then  0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.
    0 التعليقات 0 المشاركات 16 مشاهدة 0 معاينة
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