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  • BACKGROUND Distracted driving is a global epidemic, injuring and killing thousands of people every year. To better understand why people still engage in this dangerous behavior, we need to assess how the public gets informed about this issue. Knowing that many people use the internet as their primary source of initial research on topics of interest, we conducted an assessment of popular distracted driving videos found on YouTube. OBJECTIVE This study aimed to gauge the popularity of distracted driving videos and to assess the messages portrayed by classifying the content, context, and quality of the information available on YouTube. METHODS We conducted a search on YouTube using 5 different phrases related to distracted driving. Videos with more than 3000 views that mentioned or portrayed any aspect of distracted driving were identified, collected, and analyzed. We measured popularity by the number of videos uploaded annually and the number of views and reactions. Two independent researchers reviewed all the ll Ristevski. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 10.02.2020.BACKGROUND To achieve universal access to medical resources, China introduced its second health care reform in 2010, with health information technologies (HIT) as an important technical support point. OBJECTIVE This study is the first attempt to explore the unique contributions and characteristics of HIT development in Chinese hospitals from the three major aspects of hospital HIT-human resources, funding, and materials-in an all-around, multi-angled, and time-longitudinal manner, so as to serve as a reference for decision makers in China and the rest of the world when formulating HIT development strategies. METHODS A longitudinal research method is used to analyze the results of the CHIMA Annual Survey of Hospital Information System in China carried out by a Chinese national industrial association, CHIMA, from 2007 to 2018. The development characteristics of human resources, funding, and materials of HIT in China for the past 12 years are summarized. The Bass model is used to fit and predict the popularizati average level of their US counterparts in 2015 and their German counterparts in 2017 (85.26% vs. 83.8% vs. 68.4%, respectively). The results of the Bass prediction model show that Chinese hospitals will likely reach an adoption rate of 91.4% by 2020 (R2=0.95). CONCLUSIONS In more than 10 years, based on this top-down approach, China's medical care industry has accepted government instructions and implemented the unified model planned by administrative intervention. With only about one-fifth of the required funding, and about one-fourth of the required human resources per hospital as compared to the US HITECH project, China's EMR coverage in 2018 exceeded the average level of its US counterparts in 2015 and German counterparts in 2017. This experience deserves further study and analysis by other countries. ©Jun Liang, Ying Li, Zhongan Zhang, Dongxia Shen, Jie Xu, Gang Yu, Siqi Dai, Fangmin Ge, Jianbo Lei. Originally published in JMIR Medical Informatics (http//medinform.jmir.org), 10.02.2020.BACKGROUND Hepatocellular carcinoma (HCC) is a worldwide health concern because of a continued increase in cases globally; furthermore, the prognosis for patients with HCC remains poor. Transarterial chemoembolization (TACE) has been established as the standard of care for the intermediate stage of HCC; however, no therapeutic agents are available to reduce the high rate of recurrence. OBJECTIVE This study aims to evaluate the safety of alpha-fetoprotein (AFP)-derived peptides for patients with HCC post-TACE. https://www.selleckchem.com/products/Masitinib-(AB1010).html METHODS This will be an open-label, single-arm, multicenter study to evaluate the safety of AFP-derived peptides (AFP 357 and AFP 403), which contain histocompatibility antigen-A24-restricted cytotoxic T lymphocyte epitopes from tumor antigens expressed in HCC and is recognized at a high rate by lymphocytes in patients with HCC. Protocol treatment will consist of six courses of the subcutaneous administration of 3 mg each of AFP 357 and AFP 403. A total of 14 patients will be included in this study, the published in JMIR Research Protocols (http//www.researchprotocols.org), 02.02.2020.BACKGROUND Presently, 6.5 million Americans are living with heart failure (HF). These patients are expected to follow a complex self-management regimen at home. Several demographic and psychosocial factors limit patients with HF in following the prescribed self-management recommendations at home. Poor self-care is associated with increased hospital re-admissions. Under the Affordable Care Act, there are financial implications related to hospital re-admissions for hospitals and programs such as the Program of All-Inclusive Care for the Elderly (PACE) in Pinellas County, Florida. Previous studies and systematic reviews demonstrated improvement in self-management and quality of life (QoL) in patients with HF with structured telephone support (STS) and short message service text messaging (SMS). OBJECTIVE This study aimed to evaluate the effects of STS and SMS on self-care, knowledge, medication adherence, and QoL of patients with HF. METHODS A prospective quality improvement project using a pre-post design was ierformed extremely well compared with older adults. CONCLUSIONS STS and SMS were feasible to use among PACE participants with sustained benefits at 3 months. Implementing STS and SMS may serve as viable options to improve HF outcomes. Improving outcomes with HF affects hospital systems and the agencies that monitor and provide care for outpatients and those in independent or assisted-living facilities. Investigating viable options and support for implementation will improve outcomes. ©Marcia Johansson, Ponrathi Athilingam. Originally published in JMIR Aging (http//aging.jmir.org), 09.02.2020.BACKGROUND There is a need for tools to decrease cancer patients' and survivors' long-term symptom burden. Complementary strategies, such as meditation, can accompany pharmacologic therapy to improve symptoms. Although support programs with targeted content have wider reach, higher adherence, and greater impact, there are no consumer-based meditation apps designed specifically for cancer. OBJECTIVE This study aimed to gather information to advise the development of a cancer-specific meditation app in a small convenience sample of cancer patients and survivors who currently use the Calm app. METHODS Adult cancer patients and survivors who are Calm users (N=82) were recruited through the Daily Calm Facebook page. Participants completed a Web-based survey related to Calm app use and satisfaction, interest in and ideas for a cancer-specific Calm app, and demographic characteristics. Open-ended responses were inductively coded. RESULTS Participants were aged between 18 and 72 years (mean 48.60 years, SD 15.20), mostly female (77/82, 94%), white (65/79, 82%), and non-Hispanic (70/75, 93%), and reported using Calm at least 5 times per week (49/82, 60%).
    BACKGROUND Distracted driving is a global epidemic, injuring and killing thousands of people every year. To better understand why people still engage in this dangerous behavior, we need to assess how the public gets informed about this issue. Knowing that many people use the internet as their primary source of initial research on topics of interest, we conducted an assessment of popular distracted driving videos found on YouTube. OBJECTIVE This study aimed to gauge the popularity of distracted driving videos and to assess the messages portrayed by classifying the content, context, and quality of the information available on YouTube. METHODS We conducted a search on YouTube using 5 different phrases related to distracted driving. Videos with more than 3000 views that mentioned or portrayed any aspect of distracted driving were identified, collected, and analyzed. We measured popularity by the number of videos uploaded annually and the number of views and reactions. Two independent researchers reviewed all the ll Ristevski. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 10.02.2020.BACKGROUND To achieve universal access to medical resources, China introduced its second health care reform in 2010, with health information technologies (HIT) as an important technical support point. OBJECTIVE This study is the first attempt to explore the unique contributions and characteristics of HIT development in Chinese hospitals from the three major aspects of hospital HIT-human resources, funding, and materials-in an all-around, multi-angled, and time-longitudinal manner, so as to serve as a reference for decision makers in China and the rest of the world when formulating HIT development strategies. METHODS A longitudinal research method is used to analyze the results of the CHIMA Annual Survey of Hospital Information System in China carried out by a Chinese national industrial association, CHIMA, from 2007 to 2018. The development characteristics of human resources, funding, and materials of HIT in China for the past 12 years are summarized. The Bass model is used to fit and predict the popularizati average level of their US counterparts in 2015 and their German counterparts in 2017 (85.26% vs. 83.8% vs. 68.4%, respectively). The results of the Bass prediction model show that Chinese hospitals will likely reach an adoption rate of 91.4% by 2020 (R2=0.95). CONCLUSIONS In more than 10 years, based on this top-down approach, China's medical care industry has accepted government instructions and implemented the unified model planned by administrative intervention. With only about one-fifth of the required funding, and about one-fourth of the required human resources per hospital as compared to the US HITECH project, China's EMR coverage in 2018 exceeded the average level of its US counterparts in 2015 and German counterparts in 2017. This experience deserves further study and analysis by other countries. ©Jun Liang, Ying Li, Zhongan Zhang, Dongxia Shen, Jie Xu, Gang Yu, Siqi Dai, Fangmin Ge, Jianbo Lei. Originally published in JMIR Medical Informatics (http//medinform.jmir.org), 10.02.2020.BACKGROUND Hepatocellular carcinoma (HCC) is a worldwide health concern because of a continued increase in cases globally; furthermore, the prognosis for patients with HCC remains poor. Transarterial chemoembolization (TACE) has been established as the standard of care for the intermediate stage of HCC; however, no therapeutic agents are available to reduce the high rate of recurrence. OBJECTIVE This study aims to evaluate the safety of alpha-fetoprotein (AFP)-derived peptides for patients with HCC post-TACE. https://www.selleckchem.com/products/Masitinib-(AB1010).html METHODS This will be an open-label, single-arm, multicenter study to evaluate the safety of AFP-derived peptides (AFP 357 and AFP 403), which contain histocompatibility antigen-A24-restricted cytotoxic T lymphocyte epitopes from tumor antigens expressed in HCC and is recognized at a high rate by lymphocytes in patients with HCC. Protocol treatment will consist of six courses of the subcutaneous administration of 3 mg each of AFP 357 and AFP 403. A total of 14 patients will be included in this study, the published in JMIR Research Protocols (http//www.researchprotocols.org), 02.02.2020.BACKGROUND Presently, 6.5 million Americans are living with heart failure (HF). These patients are expected to follow a complex self-management regimen at home. Several demographic and psychosocial factors limit patients with HF in following the prescribed self-management recommendations at home. Poor self-care is associated with increased hospital re-admissions. Under the Affordable Care Act, there are financial implications related to hospital re-admissions for hospitals and programs such as the Program of All-Inclusive Care for the Elderly (PACE) in Pinellas County, Florida. Previous studies and systematic reviews demonstrated improvement in self-management and quality of life (QoL) in patients with HF with structured telephone support (STS) and short message service text messaging (SMS). OBJECTIVE This study aimed to evaluate the effects of STS and SMS on self-care, knowledge, medication adherence, and QoL of patients with HF. METHODS A prospective quality improvement project using a pre-post design was ierformed extremely well compared with older adults. CONCLUSIONS STS and SMS were feasible to use among PACE participants with sustained benefits at 3 months. Implementing STS and SMS may serve as viable options to improve HF outcomes. Improving outcomes with HF affects hospital systems and the agencies that monitor and provide care for outpatients and those in independent or assisted-living facilities. Investigating viable options and support for implementation will improve outcomes. ©Marcia Johansson, Ponrathi Athilingam. Originally published in JMIR Aging (http//aging.jmir.org), 09.02.2020.BACKGROUND There is a need for tools to decrease cancer patients' and survivors' long-term symptom burden. Complementary strategies, such as meditation, can accompany pharmacologic therapy to improve symptoms. Although support programs with targeted content have wider reach, higher adherence, and greater impact, there are no consumer-based meditation apps designed specifically for cancer. OBJECTIVE This study aimed to gather information to advise the development of a cancer-specific meditation app in a small convenience sample of cancer patients and survivors who currently use the Calm app. METHODS Adult cancer patients and survivors who are Calm users (N=82) were recruited through the Daily Calm Facebook page. Participants completed a Web-based survey related to Calm app use and satisfaction, interest in and ideas for a cancer-specific Calm app, and demographic characteristics. Open-ended responses were inductively coded. RESULTS Participants were aged between 18 and 72 years (mean 48.60 years, SD 15.20), mostly female (77/82, 94%), white (65/79, 82%), and non-Hispanic (70/75, 93%), and reported using Calm at least 5 times per week (49/82, 60%).
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  • In the course of their work, psychologists must make judgments and complex decisions, skills that are part of clinical reasoning. Recent models approach the analysis of such process using the dual-process theories framework. This study provides an assessment of the two systems, System 1 and System 2, in forty-five clinical psychologists with different levels of experience (novices, intermediates and experts) with the purpose of exploring their level of activation and evolution throughout such stages of expertise. According to the results, clinical psychologists mainly activate System 2, M = 70.91, SD = 6.71, than System 1, M = 60.49, SD = 3.78; $ F_\left(1,\kern0.5em 41\right)=7.99;p less then .01;\upeta^2=.163, $ when performing their clinical duties. However, no significant changes have been observed regarding the preferential use of thinking Systems 1 or 2 throughout the experience, both systems are used in a similar way in the different levels of expertise analyzed, with an increase of System 2 at the intermediate level of expertise. The results are analyzed in terms of intermediate effect and discussed focusing on the unremitting need for System 2 in psychologist work given the idiosyncratic characteristics of each case requiring treatment in the area of psychology and on the relationship of the two systems in clinical reasoning.Background Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. Methods Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. Results A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. Conclusions Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.Background Although it has been preclinically suggested that adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy could effectively treat chronic liver diseases, the hepatic engraftment of ADSCs is still extremely low, which severely limits their long-term efficacy for chronic liver diseases. This study was designed to investigate the impact of antioxidant preconditioning on hepatic engraftment efficiency and therapeutic outcomes of ADSC transplantation in liver fibrotic ****. Methods Liver fibrosis model was established by using intraperitoneal injection of carbon tetrachloride (CCl4) in the male C57BL/6 ****. Subsequently, the ADSCs with or without antioxidant pretreatment (including melatonin and reduced glutathione (GSH)) were administrated into fibrotic **** via tail vein injection. Afterwards, the ADSC transplantation efficiency was analyzed by ex vivo imaging, and the liver functions were assessed by biochemical analysis and histopathological examination, respectively. https://www.selleckchem.com/products/tradipitant.html Additionally, a typical hydrogen peroxide (H2O2)-induced cell injury model was applied to mimic the cell oxidative injury to further investigate the protective effects of antioxidant preconditioning on cell migration, proliferation, and apoptosis of ADSCs. Results Our data showed that antioxidant preconditioning could enhance the therapeutic effects of ADSCs on liver function recovery by reducing the level of AST, ALT, and TBIL, as well as the content of hepatic hydroxyproline and fibrotic area in liver tissues. Particularly, we also found that antioxidant preconditioning could enhance hepatic engraftment efficiency of ADSCs in liver fibrosis model through inhibiting oxidative injury. Conclusions Antioxidant preconditioning could effectively improve therapeutic effects of ADSC transplantation for liver fibrosis through enhancing intrahepatic engraftment efficiency by reducing oxidative injuries. These findings might provide a practical strategy for enhancing ADSC transplantation and therapeutic efficiency.Background The Onchocercidae is a family of filarial nematodes with several species of medical or veterinary importance. Microfilariae are found in the blood and/or the dermis and are usually diagnosed in humans by microscopy examination of a blood sample or skin biopsy. The main objectives of this study were to evaluate whether filariae DNA can be detected in faecal samples of wild non-human primates (NHPs), whether the detected parasites were closely related to those infecting humans and whether filarial DNA detection in faeces is associated with co-infections with nematodes (Oesophagostumum sp. and Necator sp.) known to cause blood loss while feeding on the host intestinal mucosa. Methods A total of 315 faecal samples from 6 species of NHPs from Cameroon and Gabon were analysed. PCRs targeted DNA fragments of cox1 and 12S rDNA genes, to detect the presence of filariae, and the internal transcribed spacer 2 (ITS2), to detect the presence of Oesophagostomum sp. and Necator sp. infections. Results Among the 3ildlife, their role as sylvatic reservoirs and their potential for zoonotic transmission. Future studies should focus on detecting variants circulating in both human and NHPs, and improve the molecular information to resolve or support taxonomy classification based on morphological descriptions.
    In the course of their work, psychologists must make judgments and complex decisions, skills that are part of clinical reasoning. Recent models approach the analysis of such process using the dual-process theories framework. This study provides an assessment of the two systems, System 1 and System 2, in forty-five clinical psychologists with different levels of experience (novices, intermediates and experts) with the purpose of exploring their level of activation and evolution throughout such stages of expertise. According to the results, clinical psychologists mainly activate System 2, M = 70.91, SD = 6.71, than System 1, M = 60.49, SD = 3.78; $ F_\left(1,\kern0.5em 41\right)=7.99;p less then .01;\upeta^2=.163, $ when performing their clinical duties. However, no significant changes have been observed regarding the preferential use of thinking Systems 1 or 2 throughout the experience, both systems are used in a similar way in the different levels of expertise analyzed, with an increase of System 2 at the intermediate level of expertise. The results are analyzed in terms of intermediate effect and discussed focusing on the unremitting need for System 2 in psychologist work given the idiosyncratic characteristics of each case requiring treatment in the area of psychology and on the relationship of the two systems in clinical reasoning.Background Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. Methods Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. Results A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. Conclusions Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.Background Although it has been preclinically suggested that adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy could effectively treat chronic liver diseases, the hepatic engraftment of ADSCs is still extremely low, which severely limits their long-term efficacy for chronic liver diseases. This study was designed to investigate the impact of antioxidant preconditioning on hepatic engraftment efficiency and therapeutic outcomes of ADSC transplantation in liver fibrotic mice. Methods Liver fibrosis model was established by using intraperitoneal injection of carbon tetrachloride (CCl4) in the male C57BL/6 mice. Subsequently, the ADSCs with or without antioxidant pretreatment (including melatonin and reduced glutathione (GSH)) were administrated into fibrotic mice via tail vein injection. Afterwards, the ADSC transplantation efficiency was analyzed by ex vivo imaging, and the liver functions were assessed by biochemical analysis and histopathological examination, respectively. https://www.selleckchem.com/products/tradipitant.html Additionally, a typical hydrogen peroxide (H2O2)-induced cell injury model was applied to mimic the cell oxidative injury to further investigate the protective effects of antioxidant preconditioning on cell migration, proliferation, and apoptosis of ADSCs. Results Our data showed that antioxidant preconditioning could enhance the therapeutic effects of ADSCs on liver function recovery by reducing the level of AST, ALT, and TBIL, as well as the content of hepatic hydroxyproline and fibrotic area in liver tissues. Particularly, we also found that antioxidant preconditioning could enhance hepatic engraftment efficiency of ADSCs in liver fibrosis model through inhibiting oxidative injury. Conclusions Antioxidant preconditioning could effectively improve therapeutic effects of ADSC transplantation for liver fibrosis through enhancing intrahepatic engraftment efficiency by reducing oxidative injuries. These findings might provide a practical strategy for enhancing ADSC transplantation and therapeutic efficiency.Background The Onchocercidae is a family of filarial nematodes with several species of medical or veterinary importance. Microfilariae are found in the blood and/or the dermis and are usually diagnosed in humans by microscopy examination of a blood sample or skin biopsy. The main objectives of this study were to evaluate whether filariae DNA can be detected in faecal samples of wild non-human primates (NHPs), whether the detected parasites were closely related to those infecting humans and whether filarial DNA detection in faeces is associated with co-infections with nematodes (Oesophagostumum sp. and Necator sp.) known to cause blood loss while feeding on the host intestinal mucosa. Methods A total of 315 faecal samples from 6 species of NHPs from Cameroon and Gabon were analysed. PCRs targeted DNA fragments of cox1 and 12S rDNA genes, to detect the presence of filariae, and the internal transcribed spacer 2 (ITS2), to detect the presence of Oesophagostomum sp. and Necator sp. infections. Results Among the 3ildlife, their role as sylvatic reservoirs and their potential for zoonotic transmission. Future studies should focus on detecting variants circulating in both human and NHPs, and improve the molecular information to resolve or support taxonomy classification based on morphological descriptions.
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  • The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.Diabetes mellitus (DM) contributes to intervertebral disc degeneration (IDD). The long non‑coding RNA MALAT1 has been revealed to play an important role in diabetes‑associated complications. However, the specific role of MALAT1 in diabetes‑associated IDD has not been determined. The aim of the present study was to evaluate the roles of MALAT1 in the apoptosis of cartilage endplate (CEP) cells induced by high glucose and to explore the mechanisms underlying this effect. Rat CEP cells were cultured in high‑glucose medium (25 mM glucose) for 24 or 72 h. Cells cultured in medium containing 5 mM glucose were used as a control. Flow cytometry was used to detect the degree of apoptosis. Reverse transcription‑quantitative PCR was used to measure the expression of MALAT1 mRNA. In addition, CEP cells were treated with different conditions (high glucose, high glucose + MALAT1 negative control, high glucose + MALAT1 RNAi, normal control) for 72 h. Flow cytometry was subsequently used to detect apoptosis and western blotting was used to measure the expression levels of total and phosphorylated p38. The results revealed that high glucose concentration promoted apoptosis and enhanced expression of MALAT1 in CEP cells. Furthermore, MALAT1 knockout decreased the expression levels of total and phosphorylated p38 and reduced the apoptosis of rat CEP cells. The results obtained in the present study indicated that MALAT1 may serve as an important therapeutic target for curing or delaying IDD in patients with diabetes.Vascular remodeling plays an important role in the pathogenesis of diabetic cardiovascular complications. Previous published research has indicated that microRNA‑24 (miR‑24) is involved in diabetic vascular remodeling, but the underlying molecular mechanisms have yet to be fully elucidated. The aim of the present study was to investigate whether adenovirus‑mediated miR‑24 overexpression can suppress the NOD‑like receptor family pyrin domain‑containing 3 (NLRP3)‑related inflammatory signaling pathway and attenuate diabetic vascular remodeling. The carotid arteries of diabetic rats were harvested and prepared for analysis. Reverse transcription‑quantitative PCR and western blotting assays were used to detect the expressions of related mRNAs and proteins. Morphological examinations, including hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, were also performed. The results of the present study demonstrated that miR‑24 upregulation suppressed neointimal hyperplasia and accelerated reendothelialization in the injured arteries, lowered the expression of NLRP3, apoptosis‑associated speck‑like protein, caspase‑1, proliferating cell nuclear antigen, CD45, interleukin (IL)‑1β, IL‑18 and tumor necrosis factor‑α, and increased the expression of CD31, smooth muscle (SM) α‑actin and SM‑myosin heavy chain. These data indicated that miR‑24 overexpression can attenuate vascular remodeling in a diabetic rat model through suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway.Over the last few decades, copper‑containing amine oxidase (Cu‑AO) from vegetal sources, and belonging to the class of diamine oxidase, has been documented to exhibit beneficial effects in both in vivo and ex vivo animal models of inflammatory or allergic conditions, including asthma‑like reaction and myocardial or intestinal ischemia‑reperfusion injuries. The aim of the present study was to assess the potential of vegetal Cu‑AO as an anti‑inflammatory and an antiallergic agent and to clarify its antioxidant properties. In cell‑free systems, the reactive oxygen species and reactive nitrogen species scavenging properties of Cu‑AO that is purified from Lathyrus sativus were investigated. Its effect on the formyl‑methionyl‑leucyl‑phenylalanine peptide (fMLP)‑activated cellular functions of human neutrophils were subsequently analyzed. The obtained results demonstrated that Cu‑AO is not a scavenger of superoxide or nitric oxide, and does not decompose hydrogen peroxide. However, it inhibits the fMLP‑dependent superoxide generation, elastase release and cell migration, and interferes with the process of calcium flux, supporting the idea that plant Cu‑AO can interact with human neutrophils to modulate their inflammatory function. Therefore, the importance of these properties on the possible use of vegetal Cu‑AO to control inflammatory conditions, particularly intestinal inflammation, is discussed in the current study.Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR‑106b‑5p on APE was demonstrated in platelet‑derived growth factor (PDGF)‑induced PASMCs in vitro and in an APE‑mouse model in vivo. The results showed that miR‑106b‑5p expression was downregulated in PDGF‑induced PASMCs and APE ****, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR‑106b‑5p agomiR, and increased following treatment with miR‑106b‑5p antagomiR. miR‑106b‑5p targeted the 3' untranslated region of NOR‑1 mRNA and reduced NOR1 expression. https://www.selleckchem.com/products/dn02.html NOR1 overexpression reversed the effects of miR‑106‑5p on PDGF‑induced PASMCs. The functional roles of miR‑106b‑5p in PDGF‑induced PASMCs and an APE mouse‑model, and the underlying molecular mechanisms were evaluated. AgomiR‑106b‑5p improved APE‑induced mortality and pulmonary vascular proliferation in ****. These data suggest that miR‑106‑5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF‑induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.
    The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.Diabetes mellitus (DM) contributes to intervertebral disc degeneration (IDD). The long non‑coding RNA MALAT1 has been revealed to play an important role in diabetes‑associated complications. However, the specific role of MALAT1 in diabetes‑associated IDD has not been determined. The aim of the present study was to evaluate the roles of MALAT1 in the apoptosis of cartilage endplate (CEP) cells induced by high glucose and to explore the mechanisms underlying this effect. Rat CEP cells were cultured in high‑glucose medium (25 mM glucose) for 24 or 72 h. Cells cultured in medium containing 5 mM glucose were used as a control. Flow cytometry was used to detect the degree of apoptosis. Reverse transcription‑quantitative PCR was used to measure the expression of MALAT1 mRNA. In addition, CEP cells were treated with different conditions (high glucose, high glucose + MALAT1 negative control, high glucose + MALAT1 RNAi, normal control) for 72 h. Flow cytometry was subsequently used to detect apoptosis and western blotting was used to measure the expression levels of total and phosphorylated p38. The results revealed that high glucose concentration promoted apoptosis and enhanced expression of MALAT1 in CEP cells. Furthermore, MALAT1 knockout decreased the expression levels of total and phosphorylated p38 and reduced the apoptosis of rat CEP cells. The results obtained in the present study indicated that MALAT1 may serve as an important therapeutic target for curing or delaying IDD in patients with diabetes.Vascular remodeling plays an important role in the pathogenesis of diabetic cardiovascular complications. Previous published research has indicated that microRNA‑24 (miR‑24) is involved in diabetic vascular remodeling, but the underlying molecular mechanisms have yet to be fully elucidated. The aim of the present study was to investigate whether adenovirus‑mediated miR‑24 overexpression can suppress the NOD‑like receptor family pyrin domain‑containing 3 (NLRP3)‑related inflammatory signaling pathway and attenuate diabetic vascular remodeling. The carotid arteries of diabetic rats were harvested and prepared for analysis. Reverse transcription‑quantitative PCR and western blotting assays were used to detect the expressions of related mRNAs and proteins. Morphological examinations, including hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, were also performed. The results of the present study demonstrated that miR‑24 upregulation suppressed neointimal hyperplasia and accelerated reendothelialization in the injured arteries, lowered the expression of NLRP3, apoptosis‑associated speck‑like protein, caspase‑1, proliferating cell nuclear antigen, CD45, interleukin (IL)‑1β, IL‑18 and tumor necrosis factor‑α, and increased the expression of CD31, smooth muscle (SM) α‑actin and SM‑myosin heavy chain. These data indicated that miR‑24 overexpression can attenuate vascular remodeling in a diabetic rat model through suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway.Over the last few decades, copper‑containing amine oxidase (Cu‑AO) from vegetal sources, and belonging to the class of diamine oxidase, has been documented to exhibit beneficial effects in both in vivo and ex vivo animal models of inflammatory or allergic conditions, including asthma‑like reaction and myocardial or intestinal ischemia‑reperfusion injuries. The aim of the present study was to assess the potential of vegetal Cu‑AO as an anti‑inflammatory and an antiallergic agent and to clarify its antioxidant properties. In cell‑free systems, the reactive oxygen species and reactive nitrogen species scavenging properties of Cu‑AO that is purified from Lathyrus sativus were investigated. Its effect on the formyl‑methionyl‑leucyl‑phenylalanine peptide (fMLP)‑activated cellular functions of human neutrophils were subsequently analyzed. The obtained results demonstrated that Cu‑AO is not a scavenger of superoxide or nitric oxide, and does not decompose hydrogen peroxide. However, it inhibits the fMLP‑dependent superoxide generation, elastase release and cell migration, and interferes with the process of calcium flux, supporting the idea that plant Cu‑AO can interact with human neutrophils to modulate their inflammatory function. Therefore, the importance of these properties on the possible use of vegetal Cu‑AO to control inflammatory conditions, particularly intestinal inflammation, is discussed in the current study.Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR‑106b‑5p on APE was demonstrated in platelet‑derived growth factor (PDGF)‑induced PASMCs in vitro and in an APE‑mouse model in vivo. The results showed that miR‑106b‑5p expression was downregulated in PDGF‑induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR‑106b‑5p agomiR, and increased following treatment with miR‑106b‑5p antagomiR. miR‑106b‑5p targeted the 3' untranslated region of NOR‑1 mRNA and reduced NOR1 expression. https://www.selleckchem.com/products/dn02.html NOR1 overexpression reversed the effects of miR‑106‑5p on PDGF‑induced PASMCs. The functional roles of miR‑106b‑5p in PDGF‑induced PASMCs and an APE mouse‑model, and the underlying molecular mechanisms were evaluated. AgomiR‑106b‑5p improved APE‑induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR‑106‑5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF‑induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.
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  • Metastasis is known as a key step in cancer recurrence and could be stimulated by multiple factors. Calumenin (CALU) is one of these factors which has a direct impact on cancer metastasis and yet, its underlined mechanisms have not been completely elucidated. The current study was aimed to identify CALU co-expressed genes, their signaling pathways, and expression status within the human cancers. To this point, CALU associated genes were visualized using the Cytoscape plugin BisoGenet and annotated with the Enrichr web-based application. The list of CALU related diseases was retrieved using the DisGenNet, and cancer datasets were downloaded from The Cancer Genome Atlas (TCGA) and analyzed with the Cufflink software. ROC curve analysis was used to estimate the diagnostic accuracy of DEGs in each cancer, and the Kaplan-Meier survival analysis was performed to plot the overall survival of patients. The protein level of the signature biomarkers was measured in 40 biopsy specimens and matched adjacent normal tissues collected from CRC and lung cancer patients. Analysis of CALU co-expressed genes network in TCGA datasets indicated that the network is markedly altered in human colon (COAD) and lung (LUAD) cancers. Diagnostic accuracy estimation of differentially expressed genes showed that a gene panel consisted of CALU, AURKA, and MCM2 was able to successfully distinguish cancer tumors from healthy samples. Cancer cases with abnormal expression of the signature genes had a significantly lower survival rate than other patients. Additionally, comparison of CALU, AURKA, and MCM2 proteins between healthy samples, early and advanced tumors showed that the level of these proteins was increased through normal-carcinoma transition in both types of cancers. These data indicate that the interactions between CALU, AURKA, and MCM2 has a pivotal role in cancer development, and thereby needs to be explored in the future.American households discard a significant amount of food that represent a sizable portion of their food expenditures. https://www.selleckchem.com/products/pfi-2.html This study adds to our understanding of product attributes associated with food waste, with a focus on cosmetic deterioration during home storage. Specifically, we profile a sample of U.S. individuals by patterns of common food-related behaviors and determine the effects of product attributes on food waste tendencies at the point of consumption by distinct behavioral profiles. An interactive survey at the Minnesota State Fair (N = 333) was used to obtain measurements on food-related behavior and sociodemographic factors. The survey included a conjoint task to elicit food discard tendencies to construct the food waste proxy. The study considered cosmetic deterioration, date labels, implied shelf life, package size, and prices paid, in fresh, packaged spinach and ground beef products. Factor analysis and latent class modeling categorized the sample into two classes, revealing distinct food-related behavioral patterns. Planners, who constituted a slight majority in our sample, were likely to have established pre-shopping and in-store behavior and food management and cooking skills. Extemporaneous Consumers had inferior food handling routines and were less knowledgeable and skilled in the kitchen. Regression analysis using a random-effects tobit model showed Extemporaneous Consumers were prone to waste a greater portion of the spinach product than Planners. Otherwise, both classes showed similar increases in likelihood to discard the products, as their appearance deteriorated. Their tendency to waste increased with shorter remaining shelf life for spinach but not for ground beef, and was not affected by the date label type. Results suggest an intervention that targets a general audience designed to enhance people's skills to discern edibility of food in home storage by manipulating sensory expectations from cosmetic deterioration could be impactful in efforts to curtail food waste.Introduction Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease. Methods In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy. Results We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequhealth of people living with HIV. Trial registration ISRCTN registry (ISRCTN38386321).Transference of RNAs and ribosomes from Schwann cell-to-axon was demonstrated in normal and regenerating peripheral nerves. Previously, we have shown that RNAs transfer is dependent on F-actin cytoskeleton and Myosin Va. Here, we explored the contribution of microtubules to newly synthesized RNAs transport from Schwann cell nuclei up to nodal microvilli in sciatic nerves. Results using immunohistochemistry and quantitative confocal FRET analysis indicate that Schwann cell-derived RNAs co-localize with microtubules in Schwann cell cytoplasm. Additionally, transport of Schwann cell-derived RNAs is nocodazole and colchicine sensitive demonstrating its dependence on microtubule network integrity. Moreover, mRNAs codifying neuron-specific proteins are among Schwann cell newly synthesized RNAs population, and some of them are associated with KIF1B and KIF5B microtubules-based motors.Disruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG but increased expression in trigeminal ganglia; no changes were seen in trigeminal nucleus caudalis.
    Metastasis is known as a key step in cancer recurrence and could be stimulated by multiple factors. Calumenin (CALU) is one of these factors which has a direct impact on cancer metastasis and yet, its underlined mechanisms have not been completely elucidated. The current study was aimed to identify CALU co-expressed genes, their signaling pathways, and expression status within the human cancers. To this point, CALU associated genes were visualized using the Cytoscape plugin BisoGenet and annotated with the Enrichr web-based application. The list of CALU related diseases was retrieved using the DisGenNet, and cancer datasets were downloaded from The Cancer Genome Atlas (TCGA) and analyzed with the Cufflink software. ROC curve analysis was used to estimate the diagnostic accuracy of DEGs in each cancer, and the Kaplan-Meier survival analysis was performed to plot the overall survival of patients. The protein level of the signature biomarkers was measured in 40 biopsy specimens and matched adjacent normal tissues collected from CRC and lung cancer patients. Analysis of CALU co-expressed genes network in TCGA datasets indicated that the network is markedly altered in human colon (COAD) and lung (LUAD) cancers. Diagnostic accuracy estimation of differentially expressed genes showed that a gene panel consisted of CALU, AURKA, and MCM2 was able to successfully distinguish cancer tumors from healthy samples. Cancer cases with abnormal expression of the signature genes had a significantly lower survival rate than other patients. Additionally, comparison of CALU, AURKA, and MCM2 proteins between healthy samples, early and advanced tumors showed that the level of these proteins was increased through normal-carcinoma transition in both types of cancers. These data indicate that the interactions between CALU, AURKA, and MCM2 has a pivotal role in cancer development, and thereby needs to be explored in the future.American households discard a significant amount of food that represent a sizable portion of their food expenditures. https://www.selleckchem.com/products/pfi-2.html This study adds to our understanding of product attributes associated with food waste, with a focus on cosmetic deterioration during home storage. Specifically, we profile a sample of U.S. individuals by patterns of common food-related behaviors and determine the effects of product attributes on food waste tendencies at the point of consumption by distinct behavioral profiles. An interactive survey at the Minnesota State Fair (N = 333) was used to obtain measurements on food-related behavior and sociodemographic factors. The survey included a conjoint task to elicit food discard tendencies to construct the food waste proxy. The study considered cosmetic deterioration, date labels, implied shelf life, package size, and prices paid, in fresh, packaged spinach and ground beef products. Factor analysis and latent class modeling categorized the sample into two classes, revealing distinct food-related behavioral patterns. Planners, who constituted a slight majority in our sample, were likely to have established pre-shopping and in-store behavior and food management and cooking skills. Extemporaneous Consumers had inferior food handling routines and were less knowledgeable and skilled in the kitchen. Regression analysis using a random-effects tobit model showed Extemporaneous Consumers were prone to waste a greater portion of the spinach product than Planners. Otherwise, both classes showed similar increases in likelihood to discard the products, as their appearance deteriorated. Their tendency to waste increased with shorter remaining shelf life for spinach but not for ground beef, and was not affected by the date label type. Results suggest an intervention that targets a general audience designed to enhance people's skills to discern edibility of food in home storage by manipulating sensory expectations from cosmetic deterioration could be impactful in efforts to curtail food waste.Introduction Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease. Methods In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy. Results We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequhealth of people living with HIV. Trial registration ISRCTN registry (ISRCTN38386321).Transference of RNAs and ribosomes from Schwann cell-to-axon was demonstrated in normal and regenerating peripheral nerves. Previously, we have shown that RNAs transfer is dependent on F-actin cytoskeleton and Myosin Va. Here, we explored the contribution of microtubules to newly synthesized RNAs transport from Schwann cell nuclei up to nodal microvilli in sciatic nerves. Results using immunohistochemistry and quantitative confocal FRET analysis indicate that Schwann cell-derived RNAs co-localize with microtubules in Schwann cell cytoplasm. Additionally, transport of Schwann cell-derived RNAs is nocodazole and colchicine sensitive demonstrating its dependence on microtubule network integrity. Moreover, mRNAs codifying neuron-specific proteins are among Schwann cell newly synthesized RNAs population, and some of them are associated with KIF1B and KIF5B microtubules-based motors.Disruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG but increased expression in trigeminal ganglia; no changes were seen in trigeminal nucleus caudalis.
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  • Background Returning to work following occupational injury is a key outcome for both workers' compensation boards and injured workers. Predictive factors for returning remain unclear. Aims To describe factors associated with unsuccessful return-to-work (RTW) in a hand injury population to identify target areas through which occupational rehabilitation programmes can help injured workers achieve successful RTW outcomes. Methods Demographic data, functional, pain and psychosocial scores were recorded for injured workers discharged between April 2011 and September 2015 from a multidisciplinary upper extremity treatment programme. The primary outcome of RTW status was assessed at programme discharge. Bivariate analyses and multivariable logistic regression were used to identify factors associated with being unable to RTW. Results Of 872 participants who met the inclusion criteria, 65% were male and the mean age was 46 (standard deviation [SD] 11) years. In unadjusted bivariate analyses, the group with an unsuccessful RTW outcome had higher mean baseline pain, catastrophizing and QuickDASH scores; a higher baseline prevalence of depression, and reported a high level of pain more frequently than those who were working at discharge. In the adjusted logistic regression model, not working at baseline, higher QuickDASH score and presence of depression at baseline were independently associated with unsuccessful work status outcome. Conclusions Negative baseline work status, greater self-reported functional disability and presence of depression were associated with greater odds of unsuccessful RTW following a workplace upper extremity injury. Integrating mental healthcare provision with occupational rehabilitation is a potential programmatic approach to improve RTW.Background To investigate the spatial distribution of congenital syphilis (CS) and its association to social vulnerability indexes in northeast Brazil. Methods This was an ecological study referring to all cases of CS and CS deaths recorded in the northeast region of Brazil from 2008 to 2015. Data were obtained from three Brazilian information systems. We examined statistical correlations between CS indicators by state and municipality and their socioeconomic and social vulnerability characteristics. We used Bayesian empirical local models to identify fluctuations of the indicators. Spatial statistical tests were used to identify spatial clusters and the municipalities at high risk of CS. Results The incidence of CS ranged from 2.1 cases/1000 live births (LB) in 2008 to 6.9/1000 LB in 2015, with an annual increase of 19.9% (p less then 0.001). The mortality coefficient of CS ranged from 2.9/1000 LB in 2008 to 6.5/1000 LB in 2015, resulting in an annual increase of 15.1% (p less then 0.001). Nine spatial clusters were identified. Cases of congenital syphilis occurred in well-defined spatiotemporal clusters and in areas with high levels of social vulnerability. Conclusions CS incidence is associated with social vulnerability. CS control programmes should target spatial clusters and populations with high levels of social vulnerability.Background Past research on work engagement has focused almost exclusively on either psychological or work-related factors in almost wholly separate literature. There is therefore a need to examine how these factors collectively influence work engagement. Aims To determine levels of work engagement and to identify psychological and work-related characteristics predicting work engagement in employees in Malaysia. Methods We recruited 5235 employees from 47 public and private organizations in Malaysia who responded to an online health survey. We assessed work engagement with the 9-item Utrecht Work Engagement Scale (UWES-9) and psychological distress using the 6-item Kessler scale. We performed multiple linear regression to determine predictors of work engagement. https://www.selleckchem.com/products/l-ornithine-l-aspartate.html Results Employee mean age was 33.8 years (standard deviation [SD] ± 8.8). The mean work engagement score on the UWES-9 was 3.53 (SD ± 0.94). Eleven of 18 variables on multiple regression predicted work engagement, F(18, 4925) = 69.02, P less then 0.001, R2 = 0.201. Factors that predicted higher work engagement were age, marital status, education level, job type, job permanency, longer sleep duration, lower psychological distress and no history of workplace bullying. Conclusions Key factors associated with poorer work engagement in Malaysian employees include inadequate sleep, psychological distress and a history of workplace bullying. These are modifiable factors that individuals and employers can target to improve work engagement, ideally tailored according to occupational type.The lysine histone demethylase KDM4B is overexpressed in several types of cancers and plays dual roles in genome stability maintenance. Although KDM4B is able to recognize several histone methylations, the underlying molecular mechanism is still unknown. In this study, we purified the KDM4B chromatin-associated hybrid tudor domains (HTDs) and plant home domains (PHDs) and performed the pull-down assay to screen the tri-methyl modified histone peptides that could be efficiently recognized by KDM4B. Our results showed that both HTD alone and the combination of HTD and PHD were able to specifically bind to H3K4me3 and H4K20me3. Because H4K20me3 is essential for KDM4B's rapid recruitment to DNA damage site, we further aligned the multiple tudor peptide sequence and identified two conserved residues Y993 and W987 that are critical for KDM4B-H4K20me3 interaction. The surface plasmon resonance analysis revealed that HTD displayed a rapid H4K20me3 bind-dissociate pattern. These findings therefore provided mechanistic insights into the binding of tudor domain of KDM4B protein with H4K20me3.Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that have been verified to participate in cancer pathophysiological processes. We aim to investigate the roles of circRNAs in osteosarcoma tumorigenesis. In the present study, we showed that hsa_circ_0003732 was up-regulated in OS tissues and elevated level of hsa_circ_0003732 was linked to poor prognosis of OS patients. Functional investigation indicated that hsa_circ_0003732 promoted proliferation of OS cells. Furthermore, we identified miR-545 as the hsa_circ_0003732-associated microRNA and CCNA2 was a direct target of miR-545. In addition, hsa_circ_0003732 could elevate CCNA2 expression via miR-545, resulting in the promotion of OS cells proliferation. Altogether, our findings demonstrate that hsa_circ_0003732 promotes OS cells proliferation via miR-545/CCNA2 axis and imply hsa_circ_0003732 may be a potential prognosis biomarker and therapeutic target for OS.
    Background Returning to work following occupational injury is a key outcome for both workers' compensation boards and injured workers. Predictive factors for returning remain unclear. Aims To describe factors associated with unsuccessful return-to-work (RTW) in a hand injury population to identify target areas through which occupational rehabilitation programmes can help injured workers achieve successful RTW outcomes. Methods Demographic data, functional, pain and psychosocial scores were recorded for injured workers discharged between April 2011 and September 2015 from a multidisciplinary upper extremity treatment programme. The primary outcome of RTW status was assessed at programme discharge. Bivariate analyses and multivariable logistic regression were used to identify factors associated with being unable to RTW. Results Of 872 participants who met the inclusion criteria, 65% were male and the mean age was 46 (standard deviation [SD] 11) years. In unadjusted bivariate analyses, the group with an unsuccessful RTW outcome had higher mean baseline pain, catastrophizing and QuickDASH scores; a higher baseline prevalence of depression, and reported a high level of pain more frequently than those who were working at discharge. In the adjusted logistic regression model, not working at baseline, higher QuickDASH score and presence of depression at baseline were independently associated with unsuccessful work status outcome. Conclusions Negative baseline work status, greater self-reported functional disability and presence of depression were associated with greater odds of unsuccessful RTW following a workplace upper extremity injury. Integrating mental healthcare provision with occupational rehabilitation is a potential programmatic approach to improve RTW.Background To investigate the spatial distribution of congenital syphilis (CS) and its association to social vulnerability indexes in northeast Brazil. Methods This was an ecological study referring to all cases of CS and CS deaths recorded in the northeast region of Brazil from 2008 to 2015. Data were obtained from three Brazilian information systems. We examined statistical correlations between CS indicators by state and municipality and their socioeconomic and social vulnerability characteristics. We used Bayesian empirical local models to identify fluctuations of the indicators. Spatial statistical tests were used to identify spatial clusters and the municipalities at high risk of CS. Results The incidence of CS ranged from 2.1 cases/1000 live births (LB) in 2008 to 6.9/1000 LB in 2015, with an annual increase of 19.9% (p less then 0.001). The mortality coefficient of CS ranged from 2.9/1000 LB in 2008 to 6.5/1000 LB in 2015, resulting in an annual increase of 15.1% (p less then 0.001). Nine spatial clusters were identified. Cases of congenital syphilis occurred in well-defined spatiotemporal clusters and in areas with high levels of social vulnerability. Conclusions CS incidence is associated with social vulnerability. CS control programmes should target spatial clusters and populations with high levels of social vulnerability.Background Past research on work engagement has focused almost exclusively on either psychological or work-related factors in almost wholly separate literature. There is therefore a need to examine how these factors collectively influence work engagement. Aims To determine levels of work engagement and to identify psychological and work-related characteristics predicting work engagement in employees in Malaysia. Methods We recruited 5235 employees from 47 public and private organizations in Malaysia who responded to an online health survey. We assessed work engagement with the 9-item Utrecht Work Engagement Scale (UWES-9) and psychological distress using the 6-item Kessler scale. We performed multiple linear regression to determine predictors of work engagement. https://www.selleckchem.com/products/l-ornithine-l-aspartate.html Results Employee mean age was 33.8 years (standard deviation [SD] ± 8.8). The mean work engagement score on the UWES-9 was 3.53 (SD ± 0.94). Eleven of 18 variables on multiple regression predicted work engagement, F(18, 4925) = 69.02, P less then 0.001, R2 = 0.201. Factors that predicted higher work engagement were age, marital status, education level, job type, job permanency, longer sleep duration, lower psychological distress and no history of workplace bullying. Conclusions Key factors associated with poorer work engagement in Malaysian employees include inadequate sleep, psychological distress and a history of workplace bullying. These are modifiable factors that individuals and employers can target to improve work engagement, ideally tailored according to occupational type.The lysine histone demethylase KDM4B is overexpressed in several types of cancers and plays dual roles in genome stability maintenance. Although KDM4B is able to recognize several histone methylations, the underlying molecular mechanism is still unknown. In this study, we purified the KDM4B chromatin-associated hybrid tudor domains (HTDs) and plant home domains (PHDs) and performed the pull-down assay to screen the tri-methyl modified histone peptides that could be efficiently recognized by KDM4B. Our results showed that both HTD alone and the combination of HTD and PHD were able to specifically bind to H3K4me3 and H4K20me3. Because H4K20me3 is essential for KDM4B's rapid recruitment to DNA damage site, we further aligned the multiple tudor peptide sequence and identified two conserved residues Y993 and W987 that are critical for KDM4B-H4K20me3 interaction. The surface plasmon resonance analysis revealed that HTD displayed a rapid H4K20me3 bind-dissociate pattern. These findings therefore provided mechanistic insights into the binding of tudor domain of KDM4B protein with H4K20me3.Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that have been verified to participate in cancer pathophysiological processes. We aim to investigate the roles of circRNAs in osteosarcoma tumorigenesis. In the present study, we showed that hsa_circ_0003732 was up-regulated in OS tissues and elevated level of hsa_circ_0003732 was linked to poor prognosis of OS patients. Functional investigation indicated that hsa_circ_0003732 promoted proliferation of OS cells. Furthermore, we identified miR-545 as the hsa_circ_0003732-associated microRNA and CCNA2 was a direct target of miR-545. In addition, hsa_circ_0003732 could elevate CCNA2 expression via miR-545, resulting in the promotion of OS cells proliferation. Altogether, our findings demonstrate that hsa_circ_0003732 promotes OS cells proliferation via miR-545/CCNA2 axis and imply hsa_circ_0003732 may be a potential prognosis biomarker and therapeutic target for OS.
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  • Furthermore, 4E-BP1 regulated translation levels of inhibitory Smads, which decreased the accumulation of nuclear Smad2/3 complexes on the promoter of ACAN and Col II genes, subsequently affecting transcription of ACAN and Col II. These results demonstrated that TGF-β1-modulated phosphorylation of 4EBP1 plays a role in the expression of Col II and ACAN through differential alteration of Smad signaling pathway.Compared to level running (LR), different strategies might be implemented by runners to cope with specific challenges of graded running at different speeds. The changes in joint kinetics and kinematics associated with graded running have been investigated, but their interactions with speed are unknown. Nineteen participants ran on an instrumented treadmill at five grades (0°, ±5° and ± 10°) and three speeds (2.50, 3.33 and 4.17 m/s), while 3D motion and forces were recorded. Three speed × five-grade repeated-measures ANOVA was used to analyze kinetic and kinematic variables. A speed × grade interaction was observed for hip range of motion (ROM). Downhill running (DR) at fastest speed did not reduce ROM at the hip, compared to LR. Compared to LR, it was observed that the hip joint was responsible for a greater contribution of energy generation while running at the fastest speed at +10°. Speed × grade interactions were also observed for the energy absorption, peak moment, and peak power at the knee. Contrary to LR, running faster during UR did not require higher peak power at the knee. Finally, DR at the fastest speed did not increase peak negative power at the knee compared to LR. This study demonstrates that ankle, knee, and hip joint kinetics depend on speed and grade of running, while the effect of grade on joint kinematics was not substantially modulated by speed.Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium and a causative agent of tuberculosis (TB), a disease that kills more than 1.5 million people worldwide annually. One of the main reasons for this high mortality rate is the evolution of new Mtb strains that are resistant to available antibiotics. Therefore, new therapeutics for TB are in constant demand. Here we report the development of such inhibitors that target two DNA replication enzymes of Mtb, namely DnaG primase and DNA gyrase, which share a conserved TOPRIM fold near the inhibitors' binding site. The molecules were developed on the basis of previously reported inhibitors for T7 DNA primase that bind near the TOPRIM fold. In order to improve the physicochemical properties of the molecules as well as their inhibitory effect on primase and gyrase, 49 novel compounds were synthesized as potential drug candidates in three stages of optimization. The last stage of chemical optimization yielded two novel inhibitors for the fast-growing nonpathogenic model Mycobacterium smegmatis (Msmg).Herein we report a facile, mild reaction protocol to form carbon-carbon bonds in the absence of transition metal catalysts. We demonstrate the metal-free alkenylation reactions of aryl esters with α-diazoesters to give highly functionalized enyne products. Catalytic amounts of tris(pentafluorophenyl)borane (10-20 mol%) are employed to afford the C=C coupled products (31 examples) in good to excellent yields (36-87%). DFT studies have been undertaken to elucidate the mechanism for this alkenylation reaction.Objective Anxiety and depression are common in individuals with cancer and may impact healthcare service use and costs in this population. This study examined the effects of anxiety alone, depression alone, and comorbid anxiety and depressive disorder on healthcare use and costs among patients with cancer. Method This was a retrospective cohort analysis of administrative data of patients aged 18 or older with an International Classification of Diseases, Ninth Revision diagnosis of cancer. Key outcomes were any visit to emergency department (ED), any inpatient hospitalization, length of hospital stays, and annual healthcare costs 1 year from cancer diagnosis. Results A total of 13,426 patients were included. Relative to patients with neither anxiety nor depression, those with anxiety alone, depression alone, or comorbid anxiety and depression were more likely to experience an ED visit and be hospitalized. https://www.selleckchem.com/products/pf-06952229.html Length of hospital stays were also longer and annual healthcare costs were significantly higher in all three clinical groups. Conclusions Cancer patients with anxiety and depression were at greater risk for ED visits and hospitalizations, experienced longer hospital stays, and accrued higher healthcare costs. Future researchers should determine whether screening and treating comorbid anxiety and depression may decrease healthcare utilization and improve turnover wellbeing among cancer patients.Aim We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. Methods PIBD patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011-2018. Weight and height standard-deviation-scores (SDS) were retrieved. Mean SDS-values, SDS-change and anti-TNF status were analysed at diagnosis and during follow-up. Results 490 patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height-SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5-years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1-year and remained at the 50th -centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (p=0.036). Anti-TNF treatment (p=0.013) and surgical resection (p=0.005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1-year (-0.2 vs -0.01, p=0.22), 2-years (-0.27 vs -0.01, p=0.07) and 5-years (-0.21 vs 0.25, p=0.051). Conclusion Height was generally maintained in Crohn's disease and impaired linear growth was rare in this cohort.
    Furthermore, 4E-BP1 regulated translation levels of inhibitory Smads, which decreased the accumulation of nuclear Smad2/3 complexes on the promoter of ACAN and Col II genes, subsequently affecting transcription of ACAN and Col II. These results demonstrated that TGF-β1-modulated phosphorylation of 4EBP1 plays a role in the expression of Col II and ACAN through differential alteration of Smad signaling pathway.Compared to level running (LR), different strategies might be implemented by runners to cope with specific challenges of graded running at different speeds. The changes in joint kinetics and kinematics associated with graded running have been investigated, but their interactions with speed are unknown. Nineteen participants ran on an instrumented treadmill at five grades (0°, ±5° and ± 10°) and three speeds (2.50, 3.33 and 4.17 m/s), while 3D motion and forces were recorded. Three speed × five-grade repeated-measures ANOVA was used to analyze kinetic and kinematic variables. A speed × grade interaction was observed for hip range of motion (ROM). Downhill running (DR) at fastest speed did not reduce ROM at the hip, compared to LR. Compared to LR, it was observed that the hip joint was responsible for a greater contribution of energy generation while running at the fastest speed at +10°. Speed × grade interactions were also observed for the energy absorption, peak moment, and peak power at the knee. Contrary to LR, running faster during UR did not require higher peak power at the knee. Finally, DR at the fastest speed did not increase peak negative power at the knee compared to LR. This study demonstrates that ankle, knee, and hip joint kinetics depend on speed and grade of running, while the effect of grade on joint kinematics was not substantially modulated by speed.Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium and a causative agent of tuberculosis (TB), a disease that kills more than 1.5 million people worldwide annually. One of the main reasons for this high mortality rate is the evolution of new Mtb strains that are resistant to available antibiotics. Therefore, new therapeutics for TB are in constant demand. Here we report the development of such inhibitors that target two DNA replication enzymes of Mtb, namely DnaG primase and DNA gyrase, which share a conserved TOPRIM fold near the inhibitors' binding site. The molecules were developed on the basis of previously reported inhibitors for T7 DNA primase that bind near the TOPRIM fold. In order to improve the physicochemical properties of the molecules as well as their inhibitory effect on primase and gyrase, 49 novel compounds were synthesized as potential drug candidates in three stages of optimization. The last stage of chemical optimization yielded two novel inhibitors for the fast-growing nonpathogenic model Mycobacterium smegmatis (Msmg).Herein we report a facile, mild reaction protocol to form carbon-carbon bonds in the absence of transition metal catalysts. We demonstrate the metal-free alkenylation reactions of aryl esters with α-diazoesters to give highly functionalized enyne products. Catalytic amounts of tris(pentafluorophenyl)borane (10-20 mol%) are employed to afford the C=C coupled products (31 examples) in good to excellent yields (36-87%). DFT studies have been undertaken to elucidate the mechanism for this alkenylation reaction.Objective Anxiety and depression are common in individuals with cancer and may impact healthcare service use and costs in this population. This study examined the effects of anxiety alone, depression alone, and comorbid anxiety and depressive disorder on healthcare use and costs among patients with cancer. Method This was a retrospective cohort analysis of administrative data of patients aged 18 or older with an International Classification of Diseases, Ninth Revision diagnosis of cancer. Key outcomes were any visit to emergency department (ED), any inpatient hospitalization, length of hospital stays, and annual healthcare costs 1 year from cancer diagnosis. Results A total of 13,426 patients were included. Relative to patients with neither anxiety nor depression, those with anxiety alone, depression alone, or comorbid anxiety and depression were more likely to experience an ED visit and be hospitalized. https://www.selleckchem.com/products/pf-06952229.html Length of hospital stays were also longer and annual healthcare costs were significantly higher in all three clinical groups. Conclusions Cancer patients with anxiety and depression were at greater risk for ED visits and hospitalizations, experienced longer hospital stays, and accrued higher healthcare costs. Future researchers should determine whether screening and treating comorbid anxiety and depression may decrease healthcare utilization and improve turnover wellbeing among cancer patients.Aim We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. Methods PIBD patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011-2018. Weight and height standard-deviation-scores (SDS) were retrieved. Mean SDS-values, SDS-change and anti-TNF status were analysed at diagnosis and during follow-up. Results 490 patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height-SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5-years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1-year and remained at the 50th -centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (p=0.036). Anti-TNF treatment (p=0.013) and surgical resection (p=0.005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1-year (-0.2 vs -0.01, p=0.22), 2-years (-0.27 vs -0.01, p=0.07) and 5-years (-0.21 vs 0.25, p=0.051). Conclusion Height was generally maintained in Crohn's disease and impaired linear growth was rare in this cohort.
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  • OBJECTIVE In a previous study of patients newly enrolled in HIV care, we observed that clinicians were less likely to address emotional issues expressed by African-American patients compared to whites. We sought to verify and expand these findings in a larger group of patients established in HIV care. METHODS We used VR-CoDES to analyze transcripts from 342 audio-recorded medical visits in the United States. We used random intercept multilevel logistic regression to assess associations between patient and clinician characteristics and patterns of emotional talk. RESULTS African-American patients were less likely than others to spontaneously express emotions (OR 0.50; 95 % CI 0.29-0.85). Clinicians, who were predominantly white, were more likely to respond to emotional expressions by African-American patients explicitly (OR 1.56; 95 % CI 1.11-2.20) but less likely to offer neutral/passive responses that provide space for emotional conversation (OR 0.56; 95 % CI 0.37-0.84) and more likely to block discussion of the emotional issue (OR 2.20; 95 % CI 1.05-4.63). Emotional talk did not vary by patient age or gender. CONCLUSION These results confirm our prior findings, demonstrating less open emotional communication between African-American patients and their providers. https://www.selleckchem.com/products/SB-743921.html PRACTICE IMPLICATIONS Addressing racial differences in communicating about emotions may reduce disparities in patient-clinician relationships. Published by Elsevier B.V.The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need. Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells. PURPOSE Forearm deformity is common in hereditary multiple osteochondromas (HMO). The results of ulnar lengthening and osteochondroma excision are generally favorable, both clinically and radiographically. This study aimed to assess the clinical, radiographic, and functional results of forearm reconstruction in patients with Masada type I deformity (osteochondroma in the distal ulna with radial bowing, without radial head dislocation). METHODS A retrospective review was performed on patients with HMO who underwent surgical reconstruction for a Masada type I forearm deformity over a 10-year period. Eleven forearms in 10 patients underwent gradual ulnar lengthening with an external fixator. Age at the time of surgery was 5 to 12 years. Radiographic evaluation included ulnar shortening, radial articular angle, and carpal slip. Clinical evaluation included range of motion of the elbow and wrist. Functional outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short Fortion, improved range of motion, and better cosmesis, which future research may help to clarify. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V. PURPOSE Psittacosis is a bacterial zoonosis caused by Chlamydia (Chlamydophila) psittaci that infects birds. Although potentially fatal, infections can be reduced by controlling the source of infection. We therefore described the epidemiology of psittacosis, focusing on the infection source. METHODS We descriptively analyzed psittacosis cases reported through national surveillance in Japan from 2007 to 2016. We also analyzed Chlamydia psittaci prevalence among captive psittaciformes during the same period. RESULTS One hundred eleven cases were reported, and the annual number and notification rate of psittacosis declined. While 58% were male and the median age was 61 years, the median age differed by gender (males 63 years, females 53 years), with more female cases in those aged less then 50 years. In addition, the most common infection source differed by gender (men columbiformes; women psittaciformes). The decline in notifications was associated with a decline in psittaciformes-associated cases, with a concomitant decline in female cases. The prevalence of C. psittaci among captive psittaciformes also decreased over the period. CONCLUSIONS We found important differences in the epidemiology of psittacosis by gender, and the recent decrease in notifications correlated with decreasing C. psittaci prevalence in birds. Risk communications for psittacosis should consider the current epidemiology regarding gender, age, and infection source.
    OBJECTIVE In a previous study of patients newly enrolled in HIV care, we observed that clinicians were less likely to address emotional issues expressed by African-American patients compared to whites. We sought to verify and expand these findings in a larger group of patients established in HIV care. METHODS We used VR-CoDES to analyze transcripts from 342 audio-recorded medical visits in the United States. We used random intercept multilevel logistic regression to assess associations between patient and clinician characteristics and patterns of emotional talk. RESULTS African-American patients were less likely than others to spontaneously express emotions (OR 0.50; 95 % CI 0.29-0.85). Clinicians, who were predominantly white, were more likely to respond to emotional expressions by African-American patients explicitly (OR 1.56; 95 % CI 1.11-2.20) but less likely to offer neutral/passive responses that provide space for emotional conversation (OR 0.56; 95 % CI 0.37-0.84) and more likely to block discussion of the emotional issue (OR 2.20; 95 % CI 1.05-4.63). Emotional talk did not vary by patient age or gender. CONCLUSION These results confirm our prior findings, demonstrating less open emotional communication between African-American patients and their providers. https://www.selleckchem.com/products/SB-743921.html PRACTICE IMPLICATIONS Addressing racial differences in communicating about emotions may reduce disparities in patient-clinician relationships. Published by Elsevier B.V.The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need. Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells. PURPOSE Forearm deformity is common in hereditary multiple osteochondromas (HMO). The results of ulnar lengthening and osteochondroma excision are generally favorable, both clinically and radiographically. This study aimed to assess the clinical, radiographic, and functional results of forearm reconstruction in patients with Masada type I deformity (osteochondroma in the distal ulna with radial bowing, without radial head dislocation). METHODS A retrospective review was performed on patients with HMO who underwent surgical reconstruction for a Masada type I forearm deformity over a 10-year period. Eleven forearms in 10 patients underwent gradual ulnar lengthening with an external fixator. Age at the time of surgery was 5 to 12 years. Radiographic evaluation included ulnar shortening, radial articular angle, and carpal slip. Clinical evaluation included range of motion of the elbow and wrist. Functional outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short Fortion, improved range of motion, and better cosmesis, which future research may help to clarify. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V. PURPOSE Psittacosis is a bacterial zoonosis caused by Chlamydia (Chlamydophila) psittaci that infects birds. Although potentially fatal, infections can be reduced by controlling the source of infection. We therefore described the epidemiology of psittacosis, focusing on the infection source. METHODS We descriptively analyzed psittacosis cases reported through national surveillance in Japan from 2007 to 2016. We also analyzed Chlamydia psittaci prevalence among captive psittaciformes during the same period. RESULTS One hundred eleven cases were reported, and the annual number and notification rate of psittacosis declined. While 58% were male and the median age was 61 years, the median age differed by gender (males 63 years, females 53 years), with more female cases in those aged less then 50 years. In addition, the most common infection source differed by gender (men columbiformes; women psittaciformes). The decline in notifications was associated with a decline in psittaciformes-associated cases, with a concomitant decline in female cases. The prevalence of C. psittaci among captive psittaciformes also decreased over the period. CONCLUSIONS We found important differences in the epidemiology of psittacosis by gender, and the recent decrease in notifications correlated with decreasing C. psittaci prevalence in birds. Risk communications for psittacosis should consider the current epidemiology regarding gender, age, and infection source.
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  • peripheral microvasculature. There was no change in microvascular responsiveness to neuropeptide Y after cardiopulmonary bypass nor were there any synergistic effects of neuropeptide Y on phenylephrine-induced vasoconstriction in the skeletal muscle microvasculature.Background Early recognition of postoperative vocal cord palsy enhances postoperative care. Translaryngeal ultrasonography can assess vocal cord function accurately and noninvasively, but it is unclear whether it is feasible or accurate when done immediately after extubation in the recovery room owing to possible interference from laryngeal swelling. This study assessed the feasibility and accuracy of translaryngeal ultrasonography in this setting. Methods Consecutive patients undergoing neck operations were subjected to translaryngeal ultrasonography and flexible direct laryngoscopy 1 day before and day 7 after thyroidectomy and parathyroidectomy. Translaryngeal ultrasonography was also performed immediately after extubation in the recovery room. A standardized assessment protocol was used. Patient parameters were compared between those with assessable and unassessable vocal cords. Results Sixty-five patients (91 recurrent laryngeal nerves-at-risk) were analyzed after excluding 2 male patients who failed preoperative translaryngeal ultrasonography. Fifty-six patients underwent thyroidectomy and 9 parathyroidectomy. The median age (range) was 57 (46-69); 44 (68%) were women. Sixty-one patients (94%) had assessable bilateral vocal cords on translaryngeal ultrasonography in the recovery room. Translaryngeal ultrasonography in the recovery room findings corresponded completely with day-7 findings on direct laryngoscopy. Long operative time was associated with nonassessable vocal cords on translaryngeal ultrasonography in the recovery room (P = .026). Conclusion Very early postoperative translaryngeal ultrasonography in the recovery room after neck surgery is highly feasible and accurate. Long operative time may hinder the use of translaryngeal ultrasonography in the recovery room.Introduction To address a disjuncture between medical workforce research and policy activities in Ireland, a series of national level policy dialogues were held between policy stakeholders and researchers to promote the use of research evidence in medical workforce planning. This article reports on findings from a qualitative study of four policy dialogues (2013-2016), the aim of which was to analyse policy dialogues as a mechanism for knowledge-sharing and interaction to support medical workforce planning. Methods Descriptive qualitative study design involving in-depth interviews with policy stakeholders and researchers (n = 13) who participated in the policy dialogues; thematic analysis of interview transcripts. Findings Periodic policy dialogues, with discussion focused on research evidence, provided an enabling environment for exchange and interaction between policy stakeholders and researchers, and between policy stakeholders themselves. Findings foreground the significance of the policy-making context, in terms of how people interact during policy dialogues, and how research can potentially (or not) inform medical workforce planning. Conclusion Policy dialogues provide a mechanism for improving knowledge exchange and interaction between policy stakeholders and researchers. Situated within the policy context, policy dialogues also add value to a) policy-making processes by facilitating interactions between policy stakeholders outside the day-to-day business of formal and sometimes adversarial negotiation; b) research processes, including exposing researchers to the complexity of health workforce planning, and health policy more generally.Background The use of hormone therapy (tamoxifen and aromatase inhibitors) has been shown to increase venous thromboembolism. However, while estrogens play a crucial role in wound healing, no study has assessed the impact of tamoxifen or aromatase inhibitors on other postoperative breast reconstruction complications, including infections, necrosis, capsular contracture and seroma. As breast cancer patients undergoing Implants-ADMs breast reconstruction are often receiving hormone therapy, it is unclear whether this increased infection risk is associated with increased infections cases. Methods A prospective study was performed on patients undergoing breast reconstruction at an academic institution from 2013 to 2016. Patients were divided by use of hormone therapy at the time of surgery. Complication rates, including infections, necrosis, seroma and hematomas, were compared and analyzed using univariate and logistic regression models. Results Among a total of 112 patients (183breasts), 58 patients (91 breasts) were receiving hormone therapy and 54 patients (92 breasts) were not. The hormone therapy group had a higher incidence of postoperative mastectomy skin infection (20.7% versus 7.4%; P=0.0447), we didn't find any significant differences in necrosis. Conclusions Hormone therapy was associated with a higher incidence of Infections after breast reconstruction with ADMs and implants. The authors propose an individualized approach to the preoperative cessation of tamoxifen or aromatase inhibitors. Immediate breast reconstruction surgery with expander/direct implant and use of acellular dermal matrix does hormone therapy increases the risk of infection?Objective The objective of this study was to explore how bedside micro-decisions were made between conscious patients on mechanical ventilation in intensive care and their healthcare providers. Methods Using video recordings to collect data, we explored micro-decisions between 10 mechanically ventilated patients and 60 providers in interactions at the bedside. We first identified the types of micro-decisions before using an interpretative approach to analyze the decision-making processes and create prominent themes. Results We identified six types of bedside micro-decisions; non-invited, substituted, guided, invited, shared and self-determined decisions. https://www.selleckchem.com/products/r16.html Three themes were identified in the decision-making processes 1) being an observer versus a participant in treatment and care, 2) negotiating decisions about individualized care (such as tracheal suctioning or medication),and 3) balancing empowering activities with the need for energy restoration. Conclusion This study revealed that bedside decision-making processes in intensive care were characterized by a high degree of variability between and within patients.
    peripheral microvasculature. There was no change in microvascular responsiveness to neuropeptide Y after cardiopulmonary bypass nor were there any synergistic effects of neuropeptide Y on phenylephrine-induced vasoconstriction in the skeletal muscle microvasculature.Background Early recognition of postoperative vocal cord palsy enhances postoperative care. Translaryngeal ultrasonography can assess vocal cord function accurately and noninvasively, but it is unclear whether it is feasible or accurate when done immediately after extubation in the recovery room owing to possible interference from laryngeal swelling. This study assessed the feasibility and accuracy of translaryngeal ultrasonography in this setting. Methods Consecutive patients undergoing neck operations were subjected to translaryngeal ultrasonography and flexible direct laryngoscopy 1 day before and day 7 after thyroidectomy and parathyroidectomy. Translaryngeal ultrasonography was also performed immediately after extubation in the recovery room. A standardized assessment protocol was used. Patient parameters were compared between those with assessable and unassessable vocal cords. Results Sixty-five patients (91 recurrent laryngeal nerves-at-risk) were analyzed after excluding 2 male patients who failed preoperative translaryngeal ultrasonography. Fifty-six patients underwent thyroidectomy and 9 parathyroidectomy. The median age (range) was 57 (46-69); 44 (68%) were women. Sixty-one patients (94%) had assessable bilateral vocal cords on translaryngeal ultrasonography in the recovery room. Translaryngeal ultrasonography in the recovery room findings corresponded completely with day-7 findings on direct laryngoscopy. Long operative time was associated with nonassessable vocal cords on translaryngeal ultrasonography in the recovery room (P = .026). Conclusion Very early postoperative translaryngeal ultrasonography in the recovery room after neck surgery is highly feasible and accurate. Long operative time may hinder the use of translaryngeal ultrasonography in the recovery room.Introduction To address a disjuncture between medical workforce research and policy activities in Ireland, a series of national level policy dialogues were held between policy stakeholders and researchers to promote the use of research evidence in medical workforce planning. This article reports on findings from a qualitative study of four policy dialogues (2013-2016), the aim of which was to analyse policy dialogues as a mechanism for knowledge-sharing and interaction to support medical workforce planning. Methods Descriptive qualitative study design involving in-depth interviews with policy stakeholders and researchers (n = 13) who participated in the policy dialogues; thematic analysis of interview transcripts. Findings Periodic policy dialogues, with discussion focused on research evidence, provided an enabling environment for exchange and interaction between policy stakeholders and researchers, and between policy stakeholders themselves. Findings foreground the significance of the policy-making context, in terms of how people interact during policy dialogues, and how research can potentially (or not) inform medical workforce planning. Conclusion Policy dialogues provide a mechanism for improving knowledge exchange and interaction between policy stakeholders and researchers. Situated within the policy context, policy dialogues also add value to a) policy-making processes by facilitating interactions between policy stakeholders outside the day-to-day business of formal and sometimes adversarial negotiation; b) research processes, including exposing researchers to the complexity of health workforce planning, and health policy more generally.Background The use of hormone therapy (tamoxifen and aromatase inhibitors) has been shown to increase venous thromboembolism. However, while estrogens play a crucial role in wound healing, no study has assessed the impact of tamoxifen or aromatase inhibitors on other postoperative breast reconstruction complications, including infections, necrosis, capsular contracture and seroma. As breast cancer patients undergoing Implants-ADMs breast reconstruction are often receiving hormone therapy, it is unclear whether this increased infection risk is associated with increased infections cases. Methods A prospective study was performed on patients undergoing breast reconstruction at an academic institution from 2013 to 2016. Patients were divided by use of hormone therapy at the time of surgery. Complication rates, including infections, necrosis, seroma and hematomas, were compared and analyzed using univariate and logistic regression models. Results Among a total of 112 patients (183breasts), 58 patients (91 breasts) were receiving hormone therapy and 54 patients (92 breasts) were not. The hormone therapy group had a higher incidence of postoperative mastectomy skin infection (20.7% versus 7.4%; P=0.0447), we didn't find any significant differences in necrosis. Conclusions Hormone therapy was associated with a higher incidence of Infections after breast reconstruction with ADMs and implants. The authors propose an individualized approach to the preoperative cessation of tamoxifen or aromatase inhibitors. Immediate breast reconstruction surgery with expander/direct implant and use of acellular dermal matrix does hormone therapy increases the risk of infection?Objective The objective of this study was to explore how bedside micro-decisions were made between conscious patients on mechanical ventilation in intensive care and their healthcare providers. Methods Using video recordings to collect data, we explored micro-decisions between 10 mechanically ventilated patients and 60 providers in interactions at the bedside. We first identified the types of micro-decisions before using an interpretative approach to analyze the decision-making processes and create prominent themes. Results We identified six types of bedside micro-decisions; non-invited, substituted, guided, invited, shared and self-determined decisions. https://www.selleckchem.com/products/r16.html Three themes were identified in the decision-making processes 1) being an observer versus a participant in treatment and care, 2) negotiating decisions about individualized care (such as tracheal suctioning or medication),and 3) balancing empowering activities with the need for energy restoration. Conclusion This study revealed that bedside decision-making processes in intensive care were characterized by a high degree of variability between and within patients.
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  • The linear array's one-dimensional spatial geometry is simple but suffices for univariate direction finding, i.e., is adequate for the estimation of an incident source's direction-of-arrival relative to the linear array axis. However, this nominal one-dimensional ideality could be often physically compromised in the real world, as the constituent sensors may dislocate three-dimensionally from their nominal positions. For example, a towed array is subject to ocean-surface waves and to oceanic currents [Tichavsky and Wong (2004). IEEE Trans. Sign. Process. 52(1), 36-47]. This paper analyzes how a nominally linear array's one-dimensional direction-finding accuracy would be degraded by the three-dimensional random dislocation of the constituent sensors. This analysis derives the hybrid Cramér-Rao bound (HCRB) of the arrival-angle estimate in a closed form expressed in terms of the sensors' dislocation statistics. Surprisingly, the sensors' dislocation could improve and not necessarily degrade the HCRB, depending on the dislocation variances but also on the incident source's arrival angle and the signal-to-noise power ratio.This paper investigates the performance of active noise control (ANC) systems with two reflecting surfaces that are placed vertically on ground in parallel. It employs the modal expansion method and the boundary element method to calculate the noise reduction of the systems with infinitely large and finite size reflecting surfaces, respectively. Both experimental and simulation results show that the noise reduction of the system can be significantly increased after optimizing the surface separation distance and their locations with the sound sources. It is found that the sound radiation of the primary source can be completely reduced in principle if the surface interval is less than half the wavelength and the source line is perpendicular to the surfaces for infinitely large reflecting surfaces. https://www.selleckchem.com/products/dihexa.html Even with finite size ones, the noise reduction performance improvement is still significant compared with those without any reflecting surfaces. For example, for an ANC system with a source distance of 0.074 m, experiments achieve an improvement of 8.6 dB at 800 Hz where two 0.2 m × 0.2 m parallel reflecting surfaces are placed with a distance of 0.15 m around the system on ground. The mechanisms for the performance improvement are discussed.In noisy environments, the acoustic wave is complicated and consists of the radiated wave, the incident wave, as well as its scattering wave. Double-layered pressure measurement is introduced to the boundary element method based near field acoustic holography to recover the free field quantities. First, the incoming and outgoing propagation waves are separated by exploring the propagation property of the two waves from their source to the field with the boundary integral equation. Subsequently, the scattering wave is filtered out by considering the boundary condition of the vibrating structure. Further, a measurement on an enclosing hologram is adopted to accurately reconstruct the distribution of normal velocity on the boundary. Two sets of the system of linear equations are built on the double-layered measurements. The Schur complement equation is then applied in conjunction with the Tikhonov regularization method to obtain an optimized reconstruction. Numerical examples are set up for two representative radiators impinged by incident waves. It is demonstrated that the free field normal velocity can be correctly reconstructed even if the signal-to-noise ratio is negative. An experiment is conducted for the cubic radiator to verify the accuracy and potential for the practical reconstruction in a noisy environment.This paper is concerned with the interaction of a two-dimensional plane jet with transverse plane acoustic waves, which occur, for example, in flue instruments in the vicinity of the nozzle exit. The acoustic excitation is modeled with fluctuating boundary conditions within the framework of an incompressible simulation. This method can be easily implemented in commercial CFD software. The simulations are compared with well-documented measurement data from other authors. It is shown that the model can predict not only the growth rate but also the amplitude of the perturbation, thus it captures the key features of the jet behavior in the receptive and in the linear growth region.For cochlear-implant users with near-normal contralateral hearing, a mismatch between the frequency-to-place mapping in the two ears could produce a suboptimal performance. This study assesses tonotopic matches via binaural interactions. Dynamic interaural time-difference sensitivity was measured using bandpass-filtered pulse trains at different rates in the acoustic and implanted ear, creating binaural envelope beats. Sensitivity to beats should peak when the same tonotopic region is stimulated in both ears. All nine participants detected dynamic interaural timing differences and demonstrated some frequency selectivity. This method provides a guide to frequency-to-place mapping without compensation for inherent latency differences between the acoustic and implanted ears.Carnatic music (CM) is characterized by continuous pitch variations called gamakas, which are learned by example. Precision is measured on the points of zero-slope in gamaka- and non-gamaka-segments of the pitch curve as the standard deviation (SD) of the error in their pitch with respect to targets. Two previous techniques are considered to identify targets the nearest semitone and the most likely mean of a semi-continuous Gaussian mixture model. These targets are employed irrespective of where the points of zero-slope occur in the pitch curve. The authors propose segmenting CM pitch curves into non-overlapping components called constant-pitch notes (CPNs) and stationary points (STAs), i.e., points where the pitch curve outside the CPNs changes direction. Targets are obtained statistically from the histograms of the mean pitch-values of CPNs, anchors (CPNs adjacent to STAs), and STAs. The upper and lower quartiles of SDs of errors in long CPNs (9-15 cents), short CPNs (20-26 cents), and STAs (41-54 cents) are separable, which justifies the component-wise treatment.
    The linear array's one-dimensional spatial geometry is simple but suffices for univariate direction finding, i.e., is adequate for the estimation of an incident source's direction-of-arrival relative to the linear array axis. However, this nominal one-dimensional ideality could be often physically compromised in the real world, as the constituent sensors may dislocate three-dimensionally from their nominal positions. For example, a towed array is subject to ocean-surface waves and to oceanic currents [Tichavsky and Wong (2004). IEEE Trans. Sign. Process. 52(1), 36-47]. This paper analyzes how a nominally linear array's one-dimensional direction-finding accuracy would be degraded by the three-dimensional random dislocation of the constituent sensors. This analysis derives the hybrid Cramér-Rao bound (HCRB) of the arrival-angle estimate in a closed form expressed in terms of the sensors' dislocation statistics. Surprisingly, the sensors' dislocation could improve and not necessarily degrade the HCRB, depending on the dislocation variances but also on the incident source's arrival angle and the signal-to-noise power ratio.This paper investigates the performance of active noise control (ANC) systems with two reflecting surfaces that are placed vertically on ground in parallel. It employs the modal expansion method and the boundary element method to calculate the noise reduction of the systems with infinitely large and finite size reflecting surfaces, respectively. Both experimental and simulation results show that the noise reduction of the system can be significantly increased after optimizing the surface separation distance and their locations with the sound sources. It is found that the sound radiation of the primary source can be completely reduced in principle if the surface interval is less than half the wavelength and the source line is perpendicular to the surfaces for infinitely large reflecting surfaces. https://www.selleckchem.com/products/dihexa.html Even with finite size ones, the noise reduction performance improvement is still significant compared with those without any reflecting surfaces. For example, for an ANC system with a source distance of 0.074 m, experiments achieve an improvement of 8.6 dB at 800 Hz where two 0.2 m × 0.2 m parallel reflecting surfaces are placed with a distance of 0.15 m around the system on ground. The mechanisms for the performance improvement are discussed.In noisy environments, the acoustic wave is complicated and consists of the radiated wave, the incident wave, as well as its scattering wave. Double-layered pressure measurement is introduced to the boundary element method based near field acoustic holography to recover the free field quantities. First, the incoming and outgoing propagation waves are separated by exploring the propagation property of the two waves from their source to the field with the boundary integral equation. Subsequently, the scattering wave is filtered out by considering the boundary condition of the vibrating structure. Further, a measurement on an enclosing hologram is adopted to accurately reconstruct the distribution of normal velocity on the boundary. Two sets of the system of linear equations are built on the double-layered measurements. The Schur complement equation is then applied in conjunction with the Tikhonov regularization method to obtain an optimized reconstruction. Numerical examples are set up for two representative radiators impinged by incident waves. It is demonstrated that the free field normal velocity can be correctly reconstructed even if the signal-to-noise ratio is negative. An experiment is conducted for the cubic radiator to verify the accuracy and potential for the practical reconstruction in a noisy environment.This paper is concerned with the interaction of a two-dimensional plane jet with transverse plane acoustic waves, which occur, for example, in flue instruments in the vicinity of the nozzle exit. The acoustic excitation is modeled with fluctuating boundary conditions within the framework of an incompressible simulation. This method can be easily implemented in commercial CFD software. The simulations are compared with well-documented measurement data from other authors. It is shown that the model can predict not only the growth rate but also the amplitude of the perturbation, thus it captures the key features of the jet behavior in the receptive and in the linear growth region.For cochlear-implant users with near-normal contralateral hearing, a mismatch between the frequency-to-place mapping in the two ears could produce a suboptimal performance. This study assesses tonotopic matches via binaural interactions. Dynamic interaural time-difference sensitivity was measured using bandpass-filtered pulse trains at different rates in the acoustic and implanted ear, creating binaural envelope beats. Sensitivity to beats should peak when the same tonotopic region is stimulated in both ears. All nine participants detected dynamic interaural timing differences and demonstrated some frequency selectivity. This method provides a guide to frequency-to-place mapping without compensation for inherent latency differences between the acoustic and implanted ears.Carnatic music (CM) is characterized by continuous pitch variations called gamakas, which are learned by example. Precision is measured on the points of zero-slope in gamaka- and non-gamaka-segments of the pitch curve as the standard deviation (SD) of the error in their pitch with respect to targets. Two previous techniques are considered to identify targets the nearest semitone and the most likely mean of a semi-continuous Gaussian mixture model. These targets are employed irrespective of where the points of zero-slope occur in the pitch curve. The authors propose segmenting CM pitch curves into non-overlapping components called constant-pitch notes (CPNs) and stationary points (STAs), i.e., points where the pitch curve outside the CPNs changes direction. Targets are obtained statistically from the histograms of the mean pitch-values of CPNs, anchors (CPNs adjacent to STAs), and STAs. The upper and lower quartiles of SDs of errors in long CPNs (9-15 cents), short CPNs (20-26 cents), and STAs (41-54 cents) are separable, which justifies the component-wise treatment.
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