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  • Race was perceived as a problematic construct in the understanding of Puerto Rican identities. Racism was contextualized as part of the complicated relationship between PR and the United States and as an obstacle for adequate emergency response. Conclusions Systemic racism was perceived as a barrier to emergency and recovery response in the aftermath of natural disasters. Structural changes are required to reduce vulnerability and health inequities in PR.Purpose To explore the experiences of living with painful diabetic neuropathy (PDN) and with a group acupuncture intervention in a sample of low-income, diverse patients. Methods We conducted a randomized clinical trial of a 12-week group acupuncture intervention for PDN. Data included validated measures of patient-reported outcomes, including pain and quality of life (QOL), as well as semistructured qualitative interviews about participants' experiences with PDN and the intervention. Interview transcripts were coded and analyzed using an inductive thematic framework. Results We recruited 40 participants from diverse racial/ethnic backgrounds from a public hospital and conducted in-depth qualitative interviews with a subset of 17 participants. Participants randomized to acupuncture experienced greater decreases in pain compared with usual care as well as improved QOL. In interviews, they described a myriad of socioeconomic and personal life stressors that compounded the significant suffering and disability brought on by PDN. Those who received acupuncture were able to decrease reliance on pain medication, improve their sleep and daily function, reduce stress, and engage more with their own self-care. They noted that the acupuncture intervention also gave them hope in the face of their chronic disease. Conclusion Acupuncture is a valuable adjunct treatment for low-income and marginalized populations with PDN. In addition to reducing pain and improving QOL, acupuncture may offer powerful benefits by increasing patient activation and hope.In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin cellular chromatin states (i.e. the 'epigenome') can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, although alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mouse tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs during aging.Purpose To report the first case of a patient with chronic thyroid eye disease (TED) treated with teprotumumab. Observations A 50-year-old female with a 3-year history of Graves' disease presented with bilateral exophthalmos greatest on the left side. She was followed for 2 years with stable proptosis measurements (23mm OD, 28mm OS). Her clinical activity score (CAS) was 1 and there were no examination findings reflective of active inflammation. The patient underwent systemic treatment with teprotumumab and despite chronic TED and low CAS, she had notable improvement in proptosis (18mm OD, 22mm OS) and decrease in extraocular muscle volume as noted on orbital imaging. Conclusion and importance This case report suggests that teprotumumab may be used in patients with chronic TED and low CAS. Improvement in the proptosis and reduction in extraocular muscle volume suggest that teprotumumab may alter disease course even in patients with inactive or quiescent TED.Purpose To report an unusual case of endogenous panophthalmitis involving Candida auris and describe its clinical and histopathological features. Findings A 30 year-old man with history of human immunodeficiency virus, polysubstance abuse, syphilis, and recently treated pneumonia presented with polymicrobial endogenous panophthalmitis. Two separate ocular specimens confirmed simultaneous Pseudomonas aeruginosa and Candida auris involvement. Histopathological analysis demonstrated fulminant polymorphonuclear infiltration of all ocular tissue layers. Despite aggressive management including two intravitreal injections and enucleation, the patient died, ultimately after receiving care at four neighboring urban medical centers. Conclusions and importance Candida auris has been a recently and increasingly described pathogen leading to mortality in metropolitan hospitals worldwide. https://www.selleckchem.com/products/gliocidin.html To the authors' knowledge, Candida auris has not previously been reported with endophthalmitis or panophthalmitis. Future cases may be expected with the reported rise in Candida auris. A high suspicion of its contribution to panophthalmitis could be warranted early in the evaluation and management of profoundly immunocompromised patients, particularly those who have had sequential care at multiple neighboring metropolitan hospitals.Purpose To describe our experience of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in four eyes with infantile primary congenital glaucoma (PCG). Observations We report the first two GATT procedures performed in six-month-old infants with PCG. We also report the same procedure in two eyes of a two-year-old boy with PCG who had previous goniotomies with subsequent peripheral anterior synechiae formation. In all four eyes, the IOP remained under 20 mmHg at years three and four postoperatively, without glaucoma medication or conjunctival surgery. Conclusions and importance Our cases confirm that GATT is an alternative to traditional ab externo glaucoma surgery in PCG and can be successfully performed within the first months of life, or in infants with failed or partially functioning goniotomies, avoiding the need for invasive conjunctival or scleral surgery.
    Race was perceived as a problematic construct in the understanding of Puerto Rican identities. Racism was contextualized as part of the complicated relationship between PR and the United States and as an obstacle for adequate emergency response. Conclusions Systemic racism was perceived as a barrier to emergency and recovery response in the aftermath of natural disasters. Structural changes are required to reduce vulnerability and health inequities in PR.Purpose To explore the experiences of living with painful diabetic neuropathy (PDN) and with a group acupuncture intervention in a sample of low-income, diverse patients. Methods We conducted a randomized clinical trial of a 12-week group acupuncture intervention for PDN. Data included validated measures of patient-reported outcomes, including pain and quality of life (QOL), as well as semistructured qualitative interviews about participants' experiences with PDN and the intervention. Interview transcripts were coded and analyzed using an inductive thematic framework. Results We recruited 40 participants from diverse racial/ethnic backgrounds from a public hospital and conducted in-depth qualitative interviews with a subset of 17 participants. Participants randomized to acupuncture experienced greater decreases in pain compared with usual care as well as improved QOL. In interviews, they described a myriad of socioeconomic and personal life stressors that compounded the significant suffering and disability brought on by PDN. Those who received acupuncture were able to decrease reliance on pain medication, improve their sleep and daily function, reduce stress, and engage more with their own self-care. They noted that the acupuncture intervention also gave them hope in the face of their chronic disease. Conclusion Acupuncture is a valuable adjunct treatment for low-income and marginalized populations with PDN. In addition to reducing pain and improving QOL, acupuncture may offer powerful benefits by increasing patient activation and hope.In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin cellular chromatin states (i.e. the 'epigenome') can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, although alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mouse tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs during aging.Purpose To report the first case of a patient with chronic thyroid eye disease (TED) treated with teprotumumab. Observations A 50-year-old female with a 3-year history of Graves' disease presented with bilateral exophthalmos greatest on the left side. She was followed for 2 years with stable proptosis measurements (23mm OD, 28mm OS). Her clinical activity score (CAS) was 1 and there were no examination findings reflective of active inflammation. The patient underwent systemic treatment with teprotumumab and despite chronic TED and low CAS, she had notable improvement in proptosis (18mm OD, 22mm OS) and decrease in extraocular muscle volume as noted on orbital imaging. Conclusion and importance This case report suggests that teprotumumab may be used in patients with chronic TED and low CAS. Improvement in the proptosis and reduction in extraocular muscle volume suggest that teprotumumab may alter disease course even in patients with inactive or quiescent TED.Purpose To report an unusual case of endogenous panophthalmitis involving Candida auris and describe its clinical and histopathological features. Findings A 30 year-old man with history of human immunodeficiency virus, polysubstance abuse, syphilis, and recently treated pneumonia presented with polymicrobial endogenous panophthalmitis. Two separate ocular specimens confirmed simultaneous Pseudomonas aeruginosa and Candida auris involvement. Histopathological analysis demonstrated fulminant polymorphonuclear infiltration of all ocular tissue layers. Despite aggressive management including two intravitreal injections and enucleation, the patient died, ultimately after receiving care at four neighboring urban medical centers. Conclusions and importance Candida auris has been a recently and increasingly described pathogen leading to mortality in metropolitan hospitals worldwide. https://www.selleckchem.com/products/gliocidin.html To the authors' knowledge, Candida auris has not previously been reported with endophthalmitis or panophthalmitis. Future cases may be expected with the reported rise in Candida auris. A high suspicion of its contribution to panophthalmitis could be warranted early in the evaluation and management of profoundly immunocompromised patients, particularly those who have had sequential care at multiple neighboring metropolitan hospitals.Purpose To describe our experience of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in four eyes with infantile primary congenital glaucoma (PCG). Observations We report the first two GATT procedures performed in six-month-old infants with PCG. We also report the same procedure in two eyes of a two-year-old boy with PCG who had previous goniotomies with subsequent peripheral anterior synechiae formation. In all four eyes, the IOP remained under 20 mmHg at years three and four postoperatively, without glaucoma medication or conjunctival surgery. Conclusions and importance Our cases confirm that GATT is an alternative to traditional ab externo glaucoma surgery in PCG and can be successfully performed within the first months of life, or in infants with failed or partially functioning goniotomies, avoiding the need for invasive conjunctival or scleral surgery.
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  • BACKGROUND It is hypothesised that being a blood-feeding ectoparasite, Argulus foliaceus (Linnaeus, 1758), uses similar mechanisms for digestion and host immune evasion to those used by other haematophagous ecdysozoa, including caligid copepods (e.g. sea louse). We recently described and characterised glands associated with the feeding appendages of A. foliaceus using histological techniques. The work described in the present study is the first undertaken with the objective of identifying and partially characterising the components secreted from these glands using a proteomic approach. METHODS Argulus foliaceus parasites were sampled from the skin of rainbow trout (Oncorhynchus mykiss), from Loch Fad on the Isle of Bute, Scotland, UK. The proteins from A. foliaceus secretory/excretory products (SEPs) were collected from the supernatant of artificial freshwater conditioned with active adult parasites (n = 5-9 per ml; n = 560 total). Proteins within the SEPs were identified and characterised using LC-ESI-MS/MS site immune evasion/induction (e.g. astacin), immunomodulation (e.g. serpin) and digestion (e.g. trypsin). CONCLUSIONS To our knowledge, the present study represents the first proteomic analysis undertaken for SEPs from any branchiuran fish louse. Here we reveal possible functional roles of A. foliaceus SEPs in digestion and immunomodulation, with a number of protein families shared with other haematophagous ectoparasites. A number of apparently unique secreted proteins were identified compared to other haematophagous ecdysozoa.BACKGROUND Lipid metabolism is pivotal for the growth of apicomplexan parasites. Lipid synthesis requires bulk carbon skeleton acyl-CoAs, the transport of which depends on the acyl-CoA binding protein (ACBP). In Neospora caninum, the causative agent of neosporosis, the FASII pathway is required for growth and pathogenicity. However, little is known about the fatty acid transport mechanism in N. caninum. METHODS We have identified a cytosolic acyl-CoA binding protein, with highly conserved amino acid residues and a typical acyl-CoA binding domain in N. caninum. The recombinant NcACBP protein was expressed to verify the binding activities of NcACBP in vitro, and the heterologous expression of NcACBP in Δacbp yeast in vivo. Lipid extraction from ΔNcACBP or the wild-type of N. caninum was analyzed by GC-MS or TLC. Furthermore, transcriptome analysis was performed to compare the gene expression in different strains. RESULTS The NcACBP recombinant protein was able to specifically bind acyl-CoA esters in vitro. A yepression of multiple genes. This study provides a foundation for elucidating the molecular mechanism of lipid metabolism in N. caninum.BACKGROUND Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin. RESULTS Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision. We find that depletion of JMJD1B increases the protein levels of the histone chaperone tNASP leading to an accumulation of newly synthesized histones H3 and H4 at early steps of the histone maturation cascade, which perturbs chromatin assembly. https://www.selleckchem.com/products/pentetic-acid.html Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability. CONCLUSIONS Our data support a role for JMJD1B in fine-tuning histone supply to maintain genome integrity, opening novel avenues for cancer therapeutics.The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain homeostasis within the vasculature. Recent studies have greatly expanded our understanding of the regulation of vasculature development and vascular-related diseases at the epigenetic level, including by protein posttranslational modifications, DNA methylation, and noncoding RNAs. Integrating epigenetic mechanisms into the pathophysiologic conceptualization of complex and multifactorial vascular-related diseases may provide promising therapeutic approaches. Several reviews have presented detailed discussions of epigenetic mechanisms not including histone methylation in vascular biology. In this review, we primarily discuss histone methylation in vascular development and maturity, and in vascular diseases.An aberrant Ascaris suum infection in a domestic dog in China in 2019 is described for the first time. This pathogen is a common roundworm of pigs with few reported cases in domestic animals. Our findings suggest a wider infection range with a possible transmission of A. suum to domestic animals that interact with humans.BACKGROUND Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.
    BACKGROUND It is hypothesised that being a blood-feeding ectoparasite, Argulus foliaceus (Linnaeus, 1758), uses similar mechanisms for digestion and host immune evasion to those used by other haematophagous ecdysozoa, including caligid copepods (e.g. sea louse). We recently described and characterised glands associated with the feeding appendages of A. foliaceus using histological techniques. The work described in the present study is the first undertaken with the objective of identifying and partially characterising the components secreted from these glands using a proteomic approach. METHODS Argulus foliaceus parasites were sampled from the skin of rainbow trout (Oncorhynchus mykiss), from Loch Fad on the Isle of Bute, Scotland, UK. The proteins from A. foliaceus secretory/excretory products (SEPs) were collected from the supernatant of artificial freshwater conditioned with active adult parasites (n = 5-9 per ml; n = 560 total). Proteins within the SEPs were identified and characterised using LC-ESI-MS/MS site immune evasion/induction (e.g. astacin), immunomodulation (e.g. serpin) and digestion (e.g. trypsin). CONCLUSIONS To our knowledge, the present study represents the first proteomic analysis undertaken for SEPs from any branchiuran fish louse. Here we reveal possible functional roles of A. foliaceus SEPs in digestion and immunomodulation, with a number of protein families shared with other haematophagous ectoparasites. A number of apparently unique secreted proteins were identified compared to other haematophagous ecdysozoa.BACKGROUND Lipid metabolism is pivotal for the growth of apicomplexan parasites. Lipid synthesis requires bulk carbon skeleton acyl-CoAs, the transport of which depends on the acyl-CoA binding protein (ACBP). In Neospora caninum, the causative agent of neosporosis, the FASII pathway is required for growth and pathogenicity. However, little is known about the fatty acid transport mechanism in N. caninum. METHODS We have identified a cytosolic acyl-CoA binding protein, with highly conserved amino acid residues and a typical acyl-CoA binding domain in N. caninum. The recombinant NcACBP protein was expressed to verify the binding activities of NcACBP in vitro, and the heterologous expression of NcACBP in Δacbp yeast in vivo. Lipid extraction from ΔNcACBP or the wild-type of N. caninum was analyzed by GC-MS or TLC. Furthermore, transcriptome analysis was performed to compare the gene expression in different strains. RESULTS The NcACBP recombinant protein was able to specifically bind acyl-CoA esters in vitro. A yepression of multiple genes. This study provides a foundation for elucidating the molecular mechanism of lipid metabolism in N. caninum.BACKGROUND Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin. RESULTS Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision. We find that depletion of JMJD1B increases the protein levels of the histone chaperone tNASP leading to an accumulation of newly synthesized histones H3 and H4 at early steps of the histone maturation cascade, which perturbs chromatin assembly. https://www.selleckchem.com/products/pentetic-acid.html Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability. CONCLUSIONS Our data support a role for JMJD1B in fine-tuning histone supply to maintain genome integrity, opening novel avenues for cancer therapeutics.The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain homeostasis within the vasculature. Recent studies have greatly expanded our understanding of the regulation of vasculature development and vascular-related diseases at the epigenetic level, including by protein posttranslational modifications, DNA methylation, and noncoding RNAs. Integrating epigenetic mechanisms into the pathophysiologic conceptualization of complex and multifactorial vascular-related diseases may provide promising therapeutic approaches. Several reviews have presented detailed discussions of epigenetic mechanisms not including histone methylation in vascular biology. In this review, we primarily discuss histone methylation in vascular development and maturity, and in vascular diseases.An aberrant Ascaris suum infection in a domestic dog in China in 2019 is described for the first time. This pathogen is a common roundworm of pigs with few reported cases in domestic animals. Our findings suggest a wider infection range with a possible transmission of A. suum to domestic animals that interact with humans.BACKGROUND Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.
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  • Knowledge was associated with the 4th year of study (adjusted odds ratio [aOR] 4.1, 95% CI 1.6-10.3; P less then .001). Attitude was associated with the female sex (aOR 0.7, 95% CI 0.5-1; P=.04) and TV or radio shows (aOR 1.1, 95% CI 0.6-2.1; P=.01). Practices were associated with the ≥24 years age category (aOR 1.5, 95% CI 1.1-2.1; P=.02) and online courses (aOR 1.8, 95% CI 1.1-3.2; P=.03). In total, 592 (80%) medical students were willing to participate in frontline care if called upon. Conclusions Medical students in Uganda have sufficient knowledge of COVID-19 and will be a large reservoir for health care response when the need arises.Background Psychophysiological stress and decreased well-being are relevant issues during prolonged social isolation periods. Relaxation practices may represent helpful exercises to cope with anxiety and stressful sensations. Objective The aim of this research protocol is to test whether remote relaxation practices such as natural sounds, deep respiration, and body scan meditation promote relaxation and improved emotional state and reduce psychomotor activation and the preoccupation related to the coronavirus disease (COVID-19) pandemic. Methods The study population will consist of 3 experimental groups that will randomly receive one of 3 internet-based audio clips containing a single session of guided breathing exercise, guided body scan exercise, or natural sounds. The participants will listen to the fully automated audio clip for 7 minutes and complete pre-post self-assessment scales on their perceived relaxation, psychomotor activation, level of worry associated with COVID-19, and emotional state. At the end of the session, the participants will also be asked to provide qualitative reports on their subjective experiences. Results Analyses will be performed to test the differences in the efficacy of the different audio clips in an internet-based intervention on 252 participants (84 per group), investigating whether natural sounds or remote guided practices such as deep respiration and body scan meditation positively enhance the participants' perceived psychological state. Conclusions The study will provide information on if and to what extent guided practices can help in reducing psychological side effects related to social isolation during the COVID-19 pandemic. International registered report identifier (irrid) PRR1-10.2196/19236.Physicians, nurses, and other healthcare providers initiated the #GetMePPE movement on Twitter to spread awareness of the shortage of personal protective equipment (PPE) during the COVID-19 pandemic. Dwindling supplies, such as face masks, gowns and goggles, and inadequate production to meet increasing demands, has left healthcare workers and patients at risk. The momentum of this Twitter hashtag resulted in a petition to urge public officials to address the PPE shortage through increased funding and production. Simultaneously, GetUsPPE.org was launched by a collaborative of physicians and software engineers to develop a digital platform for the donation, request, and distribution of multi-modal sources of PPE. GetUsPPE.org and #GetMePPE merged in an attempt to combine public engagement and advocacy on social media with the coordination of PPE donation and distribution. https://www.selleckchem.com/products/lithocholic-acid.html Within ten days, over 1800 hospitals and PPE suppliers were registered in a database that allowed for the rapid coordination and distribution of scarce and in-demand materials. One month after its launch, the organization has distributed hundreds of thousands of items of PPE and built a database of over 6,000 PPE requesters[1] The call for action on social media and the rapid development of this digital tool created a productive channel for the public to contribute to the healthcare response to COVID-19 in meaningful ways. #GetMePPE and GetUsPPE.org were able to mobilize individuals and organizations outside of the healthcare system to address the unmet needs of the medical community. The success of GetUsPPE.org demonstrates the potential of digital tools as a platform for larger healthcare institutions (table 1) to rapidly address urgent issues in healthcare. In this manuscript, we outline this process and discuss key factors determining success.The distributed stabilization problem is studied in this article for a group of heterogeneous second-order agents in the strong-weak competition network containing three kinds of relationships among agents 1) cooperation; 2) strong competition; and 3) weak competition. The entire network satisfies the structural balance condition which can be partitioned into two subnetworks, while the strong and weak competitions are alternate actions on the agents from different subnetworks. To stabilize such heterogeneous networked systems in a distributed way, the switched system approach is developed and utilized in this article, where it is revealed that distributed stabilization can be achieved provided that the ratio on the activating periods of strong and weak competition is chosen appropriately. As an extension, a periodical switching law is taken into account to simplify the design process, where the periodical competition function is introduced correspondingly and several effective sufficient conditions are attained. Finally, the derived analytical results are demonstrated by performing numerical simulations.Cost-sensitive learning methods guaranteeing privacy are becoming crucial nowadays in many applications where increasing use of sensitive personal information is observed. However, there has no optimal learning scheme developed in the literature to learn cost-sensitive classifiers under constraint of enforcing differential privacy. Our approach is to first develop a unified framework for existing cost-sensitive learning methods by incorporating the weight constant and weight functions into the classical regularized empirical risk minimization framework. Then, we propose two privacy-preserving algorithms with output perturbation and objective perturbation methods, respectively, to be integrated with the cost-sensitive learning framework. We showcase how this general framework can be used analytically by deriving the privacy-preserving cost-sensitive extensions of logistic regression and support vector machine. Experimental evidence on both synthetic and real data sets verifies that the proposed algorithms can reduce the misclassification cost effectively while satisfying the privacy requirement.
    Knowledge was associated with the 4th year of study (adjusted odds ratio [aOR] 4.1, 95% CI 1.6-10.3; P less then .001). Attitude was associated with the female sex (aOR 0.7, 95% CI 0.5-1; P=.04) and TV or radio shows (aOR 1.1, 95% CI 0.6-2.1; P=.01). Practices were associated with the ≥24 years age category (aOR 1.5, 95% CI 1.1-2.1; P=.02) and online courses (aOR 1.8, 95% CI 1.1-3.2; P=.03). In total, 592 (80%) medical students were willing to participate in frontline care if called upon. Conclusions Medical students in Uganda have sufficient knowledge of COVID-19 and will be a large reservoir for health care response when the need arises.Background Psychophysiological stress and decreased well-being are relevant issues during prolonged social isolation periods. Relaxation practices may represent helpful exercises to cope with anxiety and stressful sensations. Objective The aim of this research protocol is to test whether remote relaxation practices such as natural sounds, deep respiration, and body scan meditation promote relaxation and improved emotional state and reduce psychomotor activation and the preoccupation related to the coronavirus disease (COVID-19) pandemic. Methods The study population will consist of 3 experimental groups that will randomly receive one of 3 internet-based audio clips containing a single session of guided breathing exercise, guided body scan exercise, or natural sounds. The participants will listen to the fully automated audio clip for 7 minutes and complete pre-post self-assessment scales on their perceived relaxation, psychomotor activation, level of worry associated with COVID-19, and emotional state. At the end of the session, the participants will also be asked to provide qualitative reports on their subjective experiences. Results Analyses will be performed to test the differences in the efficacy of the different audio clips in an internet-based intervention on 252 participants (84 per group), investigating whether natural sounds or remote guided practices such as deep respiration and body scan meditation positively enhance the participants' perceived psychological state. Conclusions The study will provide information on if and to what extent guided practices can help in reducing psychological side effects related to social isolation during the COVID-19 pandemic. International registered report identifier (irrid) PRR1-10.2196/19236.Physicians, nurses, and other healthcare providers initiated the #GetMePPE movement on Twitter to spread awareness of the shortage of personal protective equipment (PPE) during the COVID-19 pandemic. Dwindling supplies, such as face masks, gowns and goggles, and inadequate production to meet increasing demands, has left healthcare workers and patients at risk. The momentum of this Twitter hashtag resulted in a petition to urge public officials to address the PPE shortage through increased funding and production. Simultaneously, GetUsPPE.org was launched by a collaborative of physicians and software engineers to develop a digital platform for the donation, request, and distribution of multi-modal sources of PPE. GetUsPPE.org and #GetMePPE merged in an attempt to combine public engagement and advocacy on social media with the coordination of PPE donation and distribution. https://www.selleckchem.com/products/lithocholic-acid.html Within ten days, over 1800 hospitals and PPE suppliers were registered in a database that allowed for the rapid coordination and distribution of scarce and in-demand materials. One month after its launch, the organization has distributed hundreds of thousands of items of PPE and built a database of over 6,000 PPE requesters[1] The call for action on social media and the rapid development of this digital tool created a productive channel for the public to contribute to the healthcare response to COVID-19 in meaningful ways. #GetMePPE and GetUsPPE.org were able to mobilize individuals and organizations outside of the healthcare system to address the unmet needs of the medical community. The success of GetUsPPE.org demonstrates the potential of digital tools as a platform for larger healthcare institutions (table 1) to rapidly address urgent issues in healthcare. In this manuscript, we outline this process and discuss key factors determining success.The distributed stabilization problem is studied in this article for a group of heterogeneous second-order agents in the strong-weak competition network containing three kinds of relationships among agents 1) cooperation; 2) strong competition; and 3) weak competition. The entire network satisfies the structural balance condition which can be partitioned into two subnetworks, while the strong and weak competitions are alternate actions on the agents from different subnetworks. To stabilize such heterogeneous networked systems in a distributed way, the switched system approach is developed and utilized in this article, where it is revealed that distributed stabilization can be achieved provided that the ratio on the activating periods of strong and weak competition is chosen appropriately. As an extension, a periodical switching law is taken into account to simplify the design process, where the periodical competition function is introduced correspondingly and several effective sufficient conditions are attained. Finally, the derived analytical results are demonstrated by performing numerical simulations.Cost-sensitive learning methods guaranteeing privacy are becoming crucial nowadays in many applications where increasing use of sensitive personal information is observed. However, there has no optimal learning scheme developed in the literature to learn cost-sensitive classifiers under constraint of enforcing differential privacy. Our approach is to first develop a unified framework for existing cost-sensitive learning methods by incorporating the weight constant and weight functions into the classical regularized empirical risk minimization framework. Then, we propose two privacy-preserving algorithms with output perturbation and objective perturbation methods, respectively, to be integrated with the cost-sensitive learning framework. We showcase how this general framework can be used analytically by deriving the privacy-preserving cost-sensitive extensions of logistic regression and support vector machine. Experimental evidence on both synthetic and real data sets verifies that the proposed algorithms can reduce the misclassification cost effectively while satisfying the privacy requirement.
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  • AIMS Right heart catheterization (RHC) is indicated in all candidates for heart transplantation (HT). An acute vasodilator challenge is recommended for those with pulmonary hypertension (PH) to assess its reversibility. The effects of inhaled nitric oxide (iNO) on pulmonary and systemic haemodynamics have been reported only in small series. Our purpose was to describe the response to iNO in a larger population and its potential clinical implications. METHODS AND RESULTS From 210 RHC procedures performed between 2010 and 2019, vasodilator challenge with iNO was used in 108 patients, of which 66 had advanced heart failure undergoing assessment for HT (55±11 years old; 74.2% male gender; 43.9% ischaemic cardiomyopathy; left ventricular ejection fraction 28.4 ± 11,4%; and peak VO2 12.1 ± 3.0 mL/kg/min). iNO was administered through a tight-fitting facial mask regardless of baseline pulmonary pressures. Clinical endpoints (all-cause mortality and acute right heart failure) were assessed according to baseline haemovant, but further systematic validation is warranted in larger cohorts. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.Autism commonly aggregates in families, with twin studies estimating heritability to be around 80%. Subclinical autism-like characteristics have also been found at elevated rates in relatives of autistic probands. Physical and psychiatric conditions have been reported at elevated rates in autistic children and adults, and also in their relatives. However, to date, there has been no exploration of how aging may affect this pattern. This study examined cross-sectional data from the ongoing online PROTECT study. A total of 20,220 adults aged 50 years and older reported whether they have an autistic first-degree relative. In total, 739 older adults reported having an autistic first-degree relative (AFDR group) and 11,666 were identified as having no family history of any neurodevelopmental disorder (NFD group). The AFDR group demonstrated significantly higher frequencies of self-reported psychiatric diagnoses and a greater total number of co-occurring psychiatric diagnoses than the NFD group. Furthermore, the AFDautistic relative experienced elevated rates of most psychiatric conditions but not physical conditions. Older adults with autistic relatives may benefit from close monitoring to mitigate this susceptibility and to provide timely intervention. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.The fluorescent adenine analogue qAN4 was recently shown to possess promising photophysical properties, including a high brightness as a monomer. Here we report the synthesis of the phosphoramidite of qAN4 and its successful incorporation into DNA oligonucleotides using standard solid-phase synthesis. Circular dichroism and thermal melting studies indicate that the qAN4-modification has a stabilizing effect on the B-form of DNA. Moreover, qAN4 base-pairs selectively with thymine with mismatch penalties similar to those of mismatches of adenine. The low energy absorption band of qAN4 inside DNA has its peak around 358 nm and the emission in duplex DNA is partly quenched and blue-shifted (ca. 410 nm), compared to the monomeric form. The spectral properties of the fluorophore also show sensitivity to pH; a property that may find biological applications. Quantum yields in single-stranded DNA range from 1-29 % and in duplex DNA from 1-7 %. In combination with the absorptive properties, this gives an average brightness inside duplex DNA of 275 M-1  cm-1 , more than five times higher than the most used environment-sensitive fluorescent base analogue, 2-aminopurine. Finally, we show that qAN4 can be used to advantage as a donor for interbase FRET applications in combination with adenine analogue qAnitro as an acceptor. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.BACKGROUND Up to 10% of individuals with breast cancer (**) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high-hereditary risk for ** and offer dedicated surveillance programs according to different risks. METHODS The instrument consisted of a primary questionnaire collecting history of ** and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia-Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer-Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with **/OC for BRCA1/2 genetic testing. RESULTS Since January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers. CONCLUSIONS To our knowledge, this is the first regional population-based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary-high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Long noncoding RNAs play essential roles in colon cancer tumorigenesis. This study aimed to explore the potential function and molecular mechanisms of LINC00961 in colon cancer. qPCR results showed that LINC00961 was downregulated in colon cancer cells and tissues. Functional assays demonstrated that LINC00961 suppressed the migration and invasion of colon cancer cells in vitro. LINC00961 functioned as an endogenous sponge for miR-223-3p in colon cancer cells. SOX11 was confirmed as a target gene of miR-223-3p. The effect of miR-223-3p on colon cancer cells was then investigated. MiR-223-3p inhibition enhanced their migration and invasion. The effect of SOX11 on colon cancer cells was studied. SOX11 overexpression inhibited the invasion of colon cancer cells. LINC00961 acted as an anti-oncogene and upregulated SOX11 expression by functioning as a miR-223-3p sponge. This research revealed the molecular mechanism of LINC00961 in colon cancer. https://www.selleckchem.com/products/Vorinostat-saha.html LINC00961 might act as a potential diagnostic biomarker and therapeutic target for further clinical treatments.
    AIMS Right heart catheterization (RHC) is indicated in all candidates for heart transplantation (HT). An acute vasodilator challenge is recommended for those with pulmonary hypertension (PH) to assess its reversibility. The effects of inhaled nitric oxide (iNO) on pulmonary and systemic haemodynamics have been reported only in small series. Our purpose was to describe the response to iNO in a larger population and its potential clinical implications. METHODS AND RESULTS From 210 RHC procedures performed between 2010 and 2019, vasodilator challenge with iNO was used in 108 patients, of which 66 had advanced heart failure undergoing assessment for HT (55±11 years old; 74.2% male gender; 43.9% ischaemic cardiomyopathy; left ventricular ejection fraction 28.4 ± 11,4%; and peak VO2 12.1 ± 3.0 mL/kg/min). iNO was administered through a tight-fitting facial mask regardless of baseline pulmonary pressures. Clinical endpoints (all-cause mortality and acute right heart failure) were assessed according to baseline haemovant, but further systematic validation is warranted in larger cohorts. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.Autism commonly aggregates in families, with twin studies estimating heritability to be around 80%. Subclinical autism-like characteristics have also been found at elevated rates in relatives of autistic probands. Physical and psychiatric conditions have been reported at elevated rates in autistic children and adults, and also in their relatives. However, to date, there has been no exploration of how aging may affect this pattern. This study examined cross-sectional data from the ongoing online PROTECT study. A total of 20,220 adults aged 50 years and older reported whether they have an autistic first-degree relative. In total, 739 older adults reported having an autistic first-degree relative (AFDR group) and 11,666 were identified as having no family history of any neurodevelopmental disorder (NFD group). The AFDR group demonstrated significantly higher frequencies of self-reported psychiatric diagnoses and a greater total number of co-occurring psychiatric diagnoses than the NFD group. Furthermore, the AFDautistic relative experienced elevated rates of most psychiatric conditions but not physical conditions. Older adults with autistic relatives may benefit from close monitoring to mitigate this susceptibility and to provide timely intervention. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.The fluorescent adenine analogue qAN4 was recently shown to possess promising photophysical properties, including a high brightness as a monomer. Here we report the synthesis of the phosphoramidite of qAN4 and its successful incorporation into DNA oligonucleotides using standard solid-phase synthesis. Circular dichroism and thermal melting studies indicate that the qAN4-modification has a stabilizing effect on the B-form of DNA. Moreover, qAN4 base-pairs selectively with thymine with mismatch penalties similar to those of mismatches of adenine. The low energy absorption band of qAN4 inside DNA has its peak around 358 nm and the emission in duplex DNA is partly quenched and blue-shifted (ca. 410 nm), compared to the monomeric form. The spectral properties of the fluorophore also show sensitivity to pH; a property that may find biological applications. Quantum yields in single-stranded DNA range from 1-29 % and in duplex DNA from 1-7 %. In combination with the absorptive properties, this gives an average brightness inside duplex DNA of 275 M-1  cm-1 , more than five times higher than the most used environment-sensitive fluorescent base analogue, 2-aminopurine. Finally, we show that qAN4 can be used to advantage as a donor for interbase FRET applications in combination with adenine analogue qAnitro as an acceptor. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.BACKGROUND Up to 10% of individuals with breast cancer (BC) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high-hereditary risk for BC and offer dedicated surveillance programs according to different risks. METHODS The instrument consisted of a primary questionnaire collecting history of BC and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia-Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer-Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with BC/OC for BRCA1/2 genetic testing. RESULTS Since January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers. CONCLUSIONS To our knowledge, this is the first regional population-based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary-high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Long noncoding RNAs play essential roles in colon cancer tumorigenesis. This study aimed to explore the potential function and molecular mechanisms of LINC00961 in colon cancer. qPCR results showed that LINC00961 was downregulated in colon cancer cells and tissues. Functional assays demonstrated that LINC00961 suppressed the migration and invasion of colon cancer cells in vitro. LINC00961 functioned as an endogenous sponge for miR-223-3p in colon cancer cells. SOX11 was confirmed as a target gene of miR-223-3p. The effect of miR-223-3p on colon cancer cells was then investigated. MiR-223-3p inhibition enhanced their migration and invasion. The effect of SOX11 on colon cancer cells was studied. SOX11 overexpression inhibited the invasion of colon cancer cells. LINC00961 acted as an anti-oncogene and upregulated SOX11 expression by functioning as a miR-223-3p sponge. This research revealed the molecular mechanism of LINC00961 in colon cancer. https://www.selleckchem.com/products/Vorinostat-saha.html LINC00961 might act as a potential diagnostic biomarker and therapeutic target for further clinical treatments.
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  • Extracellular vesicles (EVs) are nanosized structures able to carry proteins, lipids and genetic material from one cell to another with critical implications in intercellular communication mechanisms. Even though the rapidly growing EVs research field has sparked great interest in the last 20 years, many biological and technical aspects still remain challenging. One of the main issues that the field is facing is the absence of consensus regarding methods for EVs concentration from biofluids and tissue culture medium. Yet, not only can classic methods be time consuming, commercialized kits are also often quite expensive, especially when research requires analyzing numerous samples or concentrating EVs from large sample volumes. In addition, EV concentration often results in either low final yield or significant contamination of the vesicle sample with proteins and protein complexes of similar densities and sizes. Eventually, low vesicle yields highly limit any further application and data reproducibility while contamination greatly impacts extensive functional studies. Hence, there is a need for accessible and sustainable methods for improved vesicle concentration as this is a critical step in any EVs-related research study. In this brief report, we describe a novel combination of three well-known methods in order to obtain moderate-to-high yields of EVs with reduced protein contamination. We believe that such methods could be of high benefits for in vitro and in vivo functional studies.This study examined the role of the ubiquitin E3-ligase RNF123 in modulating downstream NF-κB1 targets in glioblastoma (GB) tumor progression. Our findings revealed an oncogenic pathway (miR-155-5p-RNF123-NF-κB1-p50-SerpinE1) that may represent a new therapeutic target pathway for GB patients with isocitrate dehydrogenase 1 and 2 (IDH) WT (wild type). Mechanistically, we demonstrated that RNF123 is downregulated in IDH WT GB patients and leads to the reduction of p50 levels. RNA-sequencing, reverse-phase protein arrays, and in vitro functional assays on IDH WT GB cell lines with RNF123 overexpression showed that SerpinE1 was a downstream target that is negatively regulated by RNF123. SERPINE1 knockdown reduced the proliferation and invasion of IDH WT GB cell lines. Both SerpinE1 and miR-155-5p overexpression negatively modulated RNF123 expression. In clinical translational analysis, RNF123, SerpinE1, and miR-155-5p were all associated with poor outcomes in GB patients. Multivariable analysis in IDH WT GB patients showed that concurrent low RNF123 and high SerpinE1 was an independent prognostic factor in predicting poor overall survival (p less then 0.001, hazard ratio (HR) = 2.93, 95% confidence interval (CI) 1.7-5.05), and an increased risk of recurrence (p less then 0.001, relative risk (RR) = 3.56, 95% CI 1.61-7.83).Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer.Breast milk does not meet the nutritional needs of preterm infants, necessitating fortification. https://www.selleckchem.com/products/apd334.html Breast milk is particularly variable in protein content, hence standardized (fixed dosage) supplementation results in inadequate supply. This was a secondary analysis of 589 breast milk protein content measurements of 51 mothers determined by mid-infrared spectroscopy during a clinical trial of higher versus lower protein supplementation in very low birth weight infants. Mothers (and breast milk samples) were divided into a test (41 mothers) and a validation cohort (10 mothers). In the test cohort, the decrease in protein content by day of lactation was modeled resulting in the breast milk-equation (BME)). In the validation cohort, five supplementation strategies to optimize protein supply were compared standardized supplementation (adding 1.0 g (S1) or 1.42 g protein/100 mL (S2)) was compared with 'adapted' supplementation, considering variation in protein content (protein content according to Gidrewicz and Fenton (A1), to BME (A2) and to BME with adjustments at days 12 and 26 (A3)). S1 and S2 achieved 5% and 24% of adequate protein supply, while the corresponding values for A1-A3 were 89%, 96% and 95%. Adapted protein supplementation based on calculated breast milk protein content is easy, non-invasive, inexpensive and improves protein supply compared to standardized supplementation.Background and Objectives Playing competitive sports is associated with stress, especially during the starting season. Disabled athletes are additionally burdened with physical and/or emotional factors, resulting from the trauma they have experienced. The aim of the work was to assess the relationship between strategies of coping with stress and the level of education, category of disability and its duration of handcyclists before the competition. Materials and Methods 44 handcyclists with a mean age of 41.8 ± 11.6, from European countries, were divided according to the severity of mobility impairments, education and duration of the disability. The participants were asked to fill in the Mini-COPE Inventory for Measuring Coping with Stress, which provided answers in writing to some sociodemographic questions regarding age, sex, education, type of mobility impairment and duration of the disability. Results The subjects who had suffered spinal injury at the cervical section obtained the lowest scores regarding their subjective assessment of their active stress management in difficult situations (p = 0.
    Extracellular vesicles (EVs) are nanosized structures able to carry proteins, lipids and genetic material from one cell to another with critical implications in intercellular communication mechanisms. Even though the rapidly growing EVs research field has sparked great interest in the last 20 years, many biological and technical aspects still remain challenging. One of the main issues that the field is facing is the absence of consensus regarding methods for EVs concentration from biofluids and tissue culture medium. Yet, not only can classic methods be time consuming, commercialized kits are also often quite expensive, especially when research requires analyzing numerous samples or concentrating EVs from large sample volumes. In addition, EV concentration often results in either low final yield or significant contamination of the vesicle sample with proteins and protein complexes of similar densities and sizes. Eventually, low vesicle yields highly limit any further application and data reproducibility while contamination greatly impacts extensive functional studies. Hence, there is a need for accessible and sustainable methods for improved vesicle concentration as this is a critical step in any EVs-related research study. In this brief report, we describe a novel combination of three well-known methods in order to obtain moderate-to-high yields of EVs with reduced protein contamination. We believe that such methods could be of high benefits for in vitro and in vivo functional studies.This study examined the role of the ubiquitin E3-ligase RNF123 in modulating downstream NF-κB1 targets in glioblastoma (GB) tumor progression. Our findings revealed an oncogenic pathway (miR-155-5p-RNF123-NF-κB1-p50-SerpinE1) that may represent a new therapeutic target pathway for GB patients with isocitrate dehydrogenase 1 and 2 (IDH) WT (wild type). Mechanistically, we demonstrated that RNF123 is downregulated in IDH WT GB patients and leads to the reduction of p50 levels. RNA-sequencing, reverse-phase protein arrays, and in vitro functional assays on IDH WT GB cell lines with RNF123 overexpression showed that SerpinE1 was a downstream target that is negatively regulated by RNF123. SERPINE1 knockdown reduced the proliferation and invasion of IDH WT GB cell lines. Both SerpinE1 and miR-155-5p overexpression negatively modulated RNF123 expression. In clinical translational analysis, RNF123, SerpinE1, and miR-155-5p were all associated with poor outcomes in GB patients. Multivariable analysis in IDH WT GB patients showed that concurrent low RNF123 and high SerpinE1 was an independent prognostic factor in predicting poor overall survival (p less then 0.001, hazard ratio (HR) = 2.93, 95% confidence interval (CI) 1.7-5.05), and an increased risk of recurrence (p less then 0.001, relative risk (RR) = 3.56, 95% CI 1.61-7.83).Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer.Breast milk does not meet the nutritional needs of preterm infants, necessitating fortification. https://www.selleckchem.com/products/apd334.html Breast milk is particularly variable in protein content, hence standardized (fixed dosage) supplementation results in inadequate supply. This was a secondary analysis of 589 breast milk protein content measurements of 51 mothers determined by mid-infrared spectroscopy during a clinical trial of higher versus lower protein supplementation in very low birth weight infants. Mothers (and breast milk samples) were divided into a test (41 mothers) and a validation cohort (10 mothers). In the test cohort, the decrease in protein content by day of lactation was modeled resulting in the breast milk-equation (BME)). In the validation cohort, five supplementation strategies to optimize protein supply were compared standardized supplementation (adding 1.0 g (S1) or 1.42 g protein/100 mL (S2)) was compared with 'adapted' supplementation, considering variation in protein content (protein content according to Gidrewicz and Fenton (A1), to BME (A2) and to BME with adjustments at days 12 and 26 (A3)). S1 and S2 achieved 5% and 24% of adequate protein supply, while the corresponding values for A1-A3 were 89%, 96% and 95%. Adapted protein supplementation based on calculated breast milk protein content is easy, non-invasive, inexpensive and improves protein supply compared to standardized supplementation.Background and Objectives Playing competitive sports is associated with stress, especially during the starting season. Disabled athletes are additionally burdened with physical and/or emotional factors, resulting from the trauma they have experienced. The aim of the work was to assess the relationship between strategies of coping with stress and the level of education, category of disability and its duration of handcyclists before the competition. Materials and Methods 44 handcyclists with a mean age of 41.8 ± 11.6, from European countries, were divided according to the severity of mobility impairments, education and duration of the disability. The participants were asked to fill in the Mini-COPE Inventory for Measuring Coping with Stress, which provided answers in writing to some sociodemographic questions regarding age, sex, education, type of mobility impairment and duration of the disability. Results The subjects who had suffered spinal injury at the cervical section obtained the lowest scores regarding their subjective assessment of their active stress management in difficult situations (p = 0.
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  • Women who hold positive beliefs about alcohol's role in sexual experiences may be more likely to drink alcohol in large group contexts such as bars and parties than other women. These contexts may confer risk for rape. In the current article, we examined the association between sex-related alcohol expectancies and rape during college, and whether drinking in large group contexts mediates this association. College women completed surveys for seven consecutive semesters. Contrary to previous cross-sectional research, women with more positive sex-related alcohol expectancies at the start of college and women who drank alcohol more frequently in large groups at the start of college were no more likely to experience rape during college. Longitudinal research is critical to identify risk factors that may be targeted for prevention. © Copyright 2020 Springer Publishing Company, LLC.OBJECTIVES Investigate the relevance of post-traumatic stress disorder (PTSD)-linked strain sensitivity associated with exposure to violence for predicting violence outcomes among juvenile offenders during adolescence and early adulthood. METHODS This study uses the Pathways to Desistance data and to test relevant relationships. Two series of negative binomial regression models were estimated to test hypotheses, one corresponding to each period of the life course. RESULTS Results indicated that witnessed violence interacted with PTSD status in adolescence, indicating that individuals afflicted with PTSD demonstrated heightened sensitivity to this strain, manifested in increased violent offending. CONCLUSIONS Results indicate that witnessed violence may act as a trigger during adolescence, resulting in juvenile offenders with PTSD responding with violence. https://www.selleckchem.com/products/atx968.html This may have treatment implications for individuals suffering from PTSD. © Copyright 2020 Springer Publishing Company, LLC.Recent research has pointed to the need for systematic law enforcement training on domestic violence when nonfatal strangulation is involved to improve evidence-based prosecution of these potentially deadly assaults; however, virtually no research has examined the legal response to nonfatal strangulation since many states have made it a separate criminal felony. The current exploratory study examines filing, charging, and adjudication decisions of nonfatal strangulation cases over a 3-year period based on evidence documentation in law enforcement reports to explore how these cases are handled by the criminal justice system in Brevard County, Florida. Results support previous research showing the importance of training police officers and other personnel as insufficient evidence may be one possible factor limiting the prosecutors' ability to successfully prosecute domestic violence strangulation offenders to the highest extent available under the law. Implications spread across multiple disciplines. © Copyright 2020 Springer Publishing Company, LLC.Using a nationally representative sample of 791 youth, ages 8-17 at baseline, this study identified patterns over a 2-year period in specific forms of peer victimization and examined differences in the mental health consequences of those patterns. Findings show that, among the victimized, physical assault had relatively high persistence compared to other forms, while physical intimidation and emotional bullying had relatively high rates of desistence. Emotional bullying at T1 was associated with increased risk of T2 Internet harassment and Internet harassment at T1 strongly predicted T2 dating violence. Patterns of victimization over time differed in their relationship with trauma symptoms. Findings emphasized the importance of recency and the distress of new victimization experiences, rather than the chronicity or repetition of victimization. Understanding variations in peer victimization patterns and outcomes over time can help to inform interventions that better target sources of risk across adolescence. © Copyright 2020 Springer Publishing Company, LLC.The draft genome sequence of Saccharomonospora piscinae KCTC 19743T, with a size of 4,897,614 bp, was assembled into 11 scaffolds containing 4,561 open reading frames and a G+C content of 71.0 mol%. Polyketide synthase and nonribosomal peptide synthetase gene clusters, which are responsible for the biosynthesis of several biomolecules, were identified and located in different regions in the genome. Copyright © 2020 Ramírez-Durán et al.Lentibacillus sp. strain JNUCC-1 was isolated from Korean traditionally fermented anchovy sauce. The 16S rRNA sequence of JNUCC-1 showed 95.2% and 95.1% similarity to Lentibacillus populi WD4L-1T and Virgibacillus siamensis MS3-4T, respectively, indicating that it is a novel species. The whole-genome sequence, which contains 3,687,469 bp and 3,833 genes in 3 contigs, is reported. Copyright © 2020 Byun and Hyun.Genomic long reads of the interspecific grapevine rootstock cultivar 'Börner' (Vitis riparia GM183 × Vitis cinerea Arnold) were used to assemble its chloroplast and mitochondrion genome sequences. We annotated 133 chloroplast and 172 mitochondrial genes, including the RNA editing sites. The organelle genomes in 'Börner' were maternally inherited from Vitis riparia. Copyright © 2020 Frommer et al.The genome sequence of nervous necrosis virus strain HGN1910, isolated from hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), was cloned, sequenced, and characterized. Two near-complete gene segments were obtained, RNA1 and RNA2. Phylogenetic analysis shows that the virus belongs to the red-spotted grouper nervous necrosis virus genotype of betanodavirus. Copyright © 2020 Jia et al.We report the whole-genome sequence of a peste des petits ruminants virus (PPRV) from a lamb exhibiting clinical signs in Turkey in September 2018. The genome of PPRV/Turkey/Central_Anatolia/2018 shows the highest nucleotide sequence identity (97.63%) to PPRV isolated in Turkey in 2000. Copyright © 2020 Hacıoğlu et al.Enterococcus faecalis OB15 is a probiotic strain that was isolated from rigouta, a popular traditional Tunisian fermented cheese. We report here the draft genome sequence of this strain, consisting of 2,912,159 bp, with an average G+C content of 37.49%. Copyright © 2020 Baccouri et al.
    Women who hold positive beliefs about alcohol's role in sexual experiences may be more likely to drink alcohol in large group contexts such as bars and parties than other women. These contexts may confer risk for rape. In the current article, we examined the association between sex-related alcohol expectancies and rape during college, and whether drinking in large group contexts mediates this association. College women completed surveys for seven consecutive semesters. Contrary to previous cross-sectional research, women with more positive sex-related alcohol expectancies at the start of college and women who drank alcohol more frequently in large groups at the start of college were no more likely to experience rape during college. Longitudinal research is critical to identify risk factors that may be targeted for prevention. © Copyright 2020 Springer Publishing Company, LLC.OBJECTIVES Investigate the relevance of post-traumatic stress disorder (PTSD)-linked strain sensitivity associated with exposure to violence for predicting violence outcomes among juvenile offenders during adolescence and early adulthood. METHODS This study uses the Pathways to Desistance data and to test relevant relationships. Two series of negative binomial regression models were estimated to test hypotheses, one corresponding to each period of the life course. RESULTS Results indicated that witnessed violence interacted with PTSD status in adolescence, indicating that individuals afflicted with PTSD demonstrated heightened sensitivity to this strain, manifested in increased violent offending. CONCLUSIONS Results indicate that witnessed violence may act as a trigger during adolescence, resulting in juvenile offenders with PTSD responding with violence. https://www.selleckchem.com/products/atx968.html This may have treatment implications for individuals suffering from PTSD. © Copyright 2020 Springer Publishing Company, LLC.Recent research has pointed to the need for systematic law enforcement training on domestic violence when nonfatal strangulation is involved to improve evidence-based prosecution of these potentially deadly assaults; however, virtually no research has examined the legal response to nonfatal strangulation since many states have made it a separate criminal felony. The current exploratory study examines filing, charging, and adjudication decisions of nonfatal strangulation cases over a 3-year period based on evidence documentation in law enforcement reports to explore how these cases are handled by the criminal justice system in Brevard County, Florida. Results support previous research showing the importance of training police officers and other personnel as insufficient evidence may be one possible factor limiting the prosecutors' ability to successfully prosecute domestic violence strangulation offenders to the highest extent available under the law. Implications spread across multiple disciplines. © Copyright 2020 Springer Publishing Company, LLC.Using a nationally representative sample of 791 youth, ages 8-17 at baseline, this study identified patterns over a 2-year period in specific forms of peer victimization and examined differences in the mental health consequences of those patterns. Findings show that, among the victimized, physical assault had relatively high persistence compared to other forms, while physical intimidation and emotional bullying had relatively high rates of desistence. Emotional bullying at T1 was associated with increased risk of T2 Internet harassment and Internet harassment at T1 strongly predicted T2 dating violence. Patterns of victimization over time differed in their relationship with trauma symptoms. Findings emphasized the importance of recency and the distress of new victimization experiences, rather than the chronicity or repetition of victimization. Understanding variations in peer victimization patterns and outcomes over time can help to inform interventions that better target sources of risk across adolescence. © Copyright 2020 Springer Publishing Company, LLC.The draft genome sequence of Saccharomonospora piscinae KCTC 19743T, with a size of 4,897,614 bp, was assembled into 11 scaffolds containing 4,561 open reading frames and a G+C content of 71.0 mol%. Polyketide synthase and nonribosomal peptide synthetase gene clusters, which are responsible for the biosynthesis of several biomolecules, were identified and located in different regions in the genome. Copyright © 2020 Ramírez-Durán et al.Lentibacillus sp. strain JNUCC-1 was isolated from Korean traditionally fermented anchovy sauce. The 16S rRNA sequence of JNUCC-1 showed 95.2% and 95.1% similarity to Lentibacillus populi WD4L-1T and Virgibacillus siamensis MS3-4T, respectively, indicating that it is a novel species. The whole-genome sequence, which contains 3,687,469 bp and 3,833 genes in 3 contigs, is reported. Copyright © 2020 Byun and Hyun.Genomic long reads of the interspecific grapevine rootstock cultivar 'Börner' (Vitis riparia GM183 × Vitis cinerea Arnold) were used to assemble its chloroplast and mitochondrion genome sequences. We annotated 133 chloroplast and 172 mitochondrial genes, including the RNA editing sites. The organelle genomes in 'Börner' were maternally inherited from Vitis riparia. Copyright © 2020 Frommer et al.The genome sequence of nervous necrosis virus strain HGN1910, isolated from hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), was cloned, sequenced, and characterized. Two near-complete gene segments were obtained, RNA1 and RNA2. Phylogenetic analysis shows that the virus belongs to the red-spotted grouper nervous necrosis virus genotype of betanodavirus. Copyright © 2020 Jia et al.We report the whole-genome sequence of a peste des petits ruminants virus (PPRV) from a lamb exhibiting clinical signs in Turkey in September 2018. The genome of PPRV/Turkey/Central_Anatolia/2018 shows the highest nucleotide sequence identity (97.63%) to PPRV isolated in Turkey in 2000. Copyright © 2020 Hacıoğlu et al.Enterococcus faecalis OB15 is a probiotic strain that was isolated from rigouta, a popular traditional Tunisian fermented cheese. We report here the draft genome sequence of this strain, consisting of 2,912,159 bp, with an average G+C content of 37.49%. Copyright © 2020 Baccouri et al.
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  • The results suggested that irbesartan may exert myocardial protection by inhibiting the expression of the NLRP3/ASC/Caspase-1 pathway in diabetic rats.Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of naïve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent **** but not in immunodeficient ****. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.As the surveillance devices proliferate, various machine learning approaches for video anomaly detection have been attempted. We propose a hybrid deep learning model composed of a video feature extractor trained by generative adversarial network with deficient anomaly data and an anomaly detector boosted by transferring the extractor. Experiments with UCSD pedestrian dataset show that it achieves 94.4% recall and 86.4% precision, which is the competitive performance in video anomaly detection.The Temporal Sampling Framework (TSF) theorizes that the characteristic phonological difficulties of dyslexia are caused by an atypical oscillatory sampling at one or more temporal rates. The LEEDUCA study conducted a series of Electroencephalography (EEG) experiments on children listening to amplitude modulated (AM) noise with slow-rythmic prosodic (0.5-1[Formula see text]Hz), syllabic (4-8[Formula see text]Hz) or the phoneme (12-40[Formula see text]Hz) rates, aimed at detecting differences in perception of oscillatory sampling that could be associated with dyslexia. The purpose of this work is to check whether these differences exist and how they are related to children's performance in different language and cognitive tasks commonly used to detect dyslexia. To this purpose, temporal and spectral inter-channel EEG connectivity was estimated, and a denoising autoencoder (DAE) was trained to learn a low-dimensional representation of the connectivity matrices. This representation was studied via correlation and classification analysis, which revealed ability in detecting dyslexic subjects with an accuracy higher than 0.8, and balanced accuracy around 0.7. Some features of the DAE representation were significantly correlated ([Formula see text]) with children's performance in language and cognitive tasks of the phonological hypothesis category such as phonological awareness and rapid symbolic naming, as well as reading efficiency and reading comprehension. Finally, a deeper analysis of the adjacency matrix revealed a reduced bilateral connection between electrodes of the temporal lobe (roughly the primary auditory cortex) in DD subjects, as well as an increased connectivity of the F7 electrode, placed roughly on Broca's area. These results pave the way for a complementary assessment of dyslexia using more objective methodologies such as EEG.We propose a new supervised learning rule for multilayer spiking neural networks (SNNs) that use a form of temporal coding known as rank-order-coding. With this coding scheme, all neurons fire exactly one spike per stimulus, but the firing order carries information. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In particular, in the readout layer, the first neuron to fire determines the class of the stimulus. We derive a new learning rule for this sort of network, named S4NN, akin to traditional error backpropagation, yet based on latencies. We show how approximated error gradients can be computed backward in a feedforward network with any number of layers. This approach reaches state-of-the-art performance with supervised multi-fully connected layer SNNs test accuracy of 97.4% for the MNIST dataset, and 99.2% for the Caltech Face/Motorbike dataset. Yet, the neuron model that we use, nonleaky integrate-and-fire, is **** simpler than the one used in all previous works. The source codes of the proposed S4NN are publicly available at https//github.com/SRKH/S4NN.Oral vaccination offers the promise of convenient, pain-free and self-administrable vaccine delivery. This is highly attractive in response to pandemic outbreaks where rapid mass vaccination is critical. Furthermore, oral vaccination produces mucosal, as well as systemic, immune responses, which protect against infection at mucosal surfaces. As the majority of pathogens enter the body through mucosal surfaces this may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for targeting orally delivered vaccines, including the oral cavity, stomach and small intestine. Despite this, currently available oral vaccines are effectively limited to either live attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges to the delivery of subunit and nucleic acid vaccines, including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent significant advances in oral biologic delivery that offer promise as future platforms for administration of oral vaccines. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.
    The results suggested that irbesartan may exert myocardial protection by inhibiting the expression of the NLRP3/ASC/Caspase-1 pathway in diabetic rats.Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of naïve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.As the surveillance devices proliferate, various machine learning approaches for video anomaly detection have been attempted. We propose a hybrid deep learning model composed of a video feature extractor trained by generative adversarial network with deficient anomaly data and an anomaly detector boosted by transferring the extractor. Experiments with UCSD pedestrian dataset show that it achieves 94.4% recall and 86.4% precision, which is the competitive performance in video anomaly detection.The Temporal Sampling Framework (TSF) theorizes that the characteristic phonological difficulties of dyslexia are caused by an atypical oscillatory sampling at one or more temporal rates. The LEEDUCA study conducted a series of Electroencephalography (EEG) experiments on children listening to amplitude modulated (AM) noise with slow-rythmic prosodic (0.5-1[Formula see text]Hz), syllabic (4-8[Formula see text]Hz) or the phoneme (12-40[Formula see text]Hz) rates, aimed at detecting differences in perception of oscillatory sampling that could be associated with dyslexia. The purpose of this work is to check whether these differences exist and how they are related to children's performance in different language and cognitive tasks commonly used to detect dyslexia. To this purpose, temporal and spectral inter-channel EEG connectivity was estimated, and a denoising autoencoder (DAE) was trained to learn a low-dimensional representation of the connectivity matrices. This representation was studied via correlation and classification analysis, which revealed ability in detecting dyslexic subjects with an accuracy higher than 0.8, and balanced accuracy around 0.7. Some features of the DAE representation were significantly correlated ([Formula see text]) with children's performance in language and cognitive tasks of the phonological hypothesis category such as phonological awareness and rapid symbolic naming, as well as reading efficiency and reading comprehension. Finally, a deeper analysis of the adjacency matrix revealed a reduced bilateral connection between electrodes of the temporal lobe (roughly the primary auditory cortex) in DD subjects, as well as an increased connectivity of the F7 electrode, placed roughly on Broca's area. These results pave the way for a complementary assessment of dyslexia using more objective methodologies such as EEG.We propose a new supervised learning rule for multilayer spiking neural networks (SNNs) that use a form of temporal coding known as rank-order-coding. With this coding scheme, all neurons fire exactly one spike per stimulus, but the firing order carries information. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In particular, in the readout layer, the first neuron to fire determines the class of the stimulus. We derive a new learning rule for this sort of network, named S4NN, akin to traditional error backpropagation, yet based on latencies. We show how approximated error gradients can be computed backward in a feedforward network with any number of layers. This approach reaches state-of-the-art performance with supervised multi-fully connected layer SNNs test accuracy of 97.4% for the MNIST dataset, and 99.2% for the Caltech Face/Motorbike dataset. Yet, the neuron model that we use, nonleaky integrate-and-fire, is much simpler than the one used in all previous works. The source codes of the proposed S4NN are publicly available at https//github.com/SRKH/S4NN.Oral vaccination offers the promise of convenient, pain-free and self-administrable vaccine delivery. This is highly attractive in response to pandemic outbreaks where rapid mass vaccination is critical. Furthermore, oral vaccination produces mucosal, as well as systemic, immune responses, which protect against infection at mucosal surfaces. As the majority of pathogens enter the body through mucosal surfaces this may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for targeting orally delivered vaccines, including the oral cavity, stomach and small intestine. Despite this, currently available oral vaccines are effectively limited to either live attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges to the delivery of subunit and nucleic acid vaccines, including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent significant advances in oral biologic delivery that offer promise as future platforms for administration of oral vaccines. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.
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  • The biochemical assays further revealed that the levels of total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) were reduced, while the activity of superoxide dismutase (***) was increased after apigenin treatment in hyperlipidemic rats. Moreover, we performed histopathological investigations and found that the lipidic deposition patterns were recovered and the amount of lipid vacuoles was significantly reduced in apigenin-treated hyperlipidemic rat liver. Western blotting assay showed that the expression of low-density lipoprotein receptor (LDLR) and lecithin-cholesterol acyltransferase (LCAT) were up-regulated in the apigenin-treated samples. Overall, our results demonstrated that the apigenin isolated from G. veitchiorum flower exhibited radical scavenging activities, and reversed the high fat diet-induced oxidative damage in rats. Its antioxidative activities are probably achieved via LDLR-LCAT signaling pathway.Biogenic amines are the important markers for food spoilage, thus, an on-package sensor for biogenic amine detection is crucial for food quality control. A dual detection platform including colorimetry and LDI-MS was developed for screening and quantitative determining of biogenic amines. Porous PLA film, was fabricated using calcium carbonate nanoparticles to enhance film porosity leading to increased surface area of colorimetric sensor. The color intensity significantly increases depending upon the enhanced analyte concentration with a linear range of 2.0-10.0 mg/mL for putrescine, and 0.1-6.0 mg/mL for cadaverine. On another layer, graphene oxide paper was applied as an LDI-MS substrate for sensitive quantification of biogenic amines. LOD values measured on graphene oxide coated side by LDI-MS were found to be 0.07 pM and 0.02 pM for putrescine and cadaverine, respectively. This platform was successfully applied for the detection of biogenic amines in pork samples with satisfactory results.The processing and digestive stability of ethanolic extracts from four Thai rice bran varieties, namely Khao Dawk Mali 105, Hom Nil, Kiaw Ngu, and Leum Pua, were assessed by applying different thermal and pH conditions, as well as in vitro gastrointestinal digestion models. High-performance liquid chromatography, Folin-Ciocalteu analysis, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) assays were used to determine the chemical composition, total phenolic content (TPC), and antioxidant activity. Thermal treatment at 100 °C for 15 min induced the degradation of phenolic components and TPC, whereas the antioxidant activities measured by DPPH and FRAP assays remained stable after the heat treatment. Higher phenolic content and antioxidant activity values were observed in the extracts incubated at acidic pH levels of 3 and 5. After simulated digestion, all extracts exhibited the decrease of phenolic compounds and anthocyanin contents, as well as antioxidant activities.It has been proven that at increased temperature, sterols can undergo various chemical reactions e.g., oxidation, dehydrogenation, dehydration and polymerisation. The objectives of this study are to prove the existence of dimers and to quantitatively analyse the dimers (3β,3'β-disteryl ethers). Sterol-rich samples were heated at 180 °C, 200 °C and 220 °C for 1 to 5 h. Quantitative analyses of the 3β,3'β-disteryl ethers were conducted using liquid extraction, solid-phase extraction and gas chromatography coupled with mass spectrometry. Additionally, for the analyses, suitable standards were synthetized from native sterols. To identify the mechanism of 3β,3'β-disteryl ether formation at high temperatures, an attempt was made to use the proposed synthesis method. Additionally, due to the association of sterols and sterol derivatives with atherosclerosis, preliminary studies with synthetized 3β,3'β-disteryl ethers on endothelial cells were conducted.Polysaccharides are a major active component of Porphyra haitanensis, which is an important food source in many countries. Four different molecular-weight fractions, namely PHPD-I (329 kDa), PHPD-II (203 kDa), PHPD-III (128 kDa), and PHPD-IV (10 kDa), were obtained from P. haitanensis polysaccharides by degradation using the H2O2/ascorbic acid system. PHPD-IV elicited the highest level of antioxidant and immunostimulatory activity among the four fractions. https://www.selleckchem.com/products/IC-87114.html PHPD-IV was purified by DEAE-cellulose column and five fractions were obtained, designated PHPD-IV-1-PHPD-IV-5. PHPD-IV-4 displayed the greatest biological activity by up-regulating the phosphorylation of MAPK signalling molecules. PHPD-IV-4 was further purified, and its structure was characterized by monosaccharide composition and 1/2D-NMR analysis. The result revealed that PHPD-IV-4 was repeated units of → 3) β-d-galactose (1 → 4) 3, 6-anhydro-α-l-galactose (1→, and → 3) β-d-galactose (1 → 4) α-l-galactose-6-S (1→. This study provides a theoretical basis for the utilisation and structure-activity assessment of P. haitanensis polysaccharides.The role of polyphenol oxidase (PPO) in the browning of fresh wet noodle sheets (FWNS) was discussed. To release the chemical formation mechanism of the dark spots formed on FWNS, the reconstituted FWNS and PPO-catechol reaction systems were prepared. Different from the overall color change of FWNS, almost all the melanins in dark spots were indirect products of PPO catalysis. The PPO catalytic dehydrogenation was an essential step for the formation of dark spots, but once the phenol dehydrogenation products were formed, the dark spots could still form through a further polymerization process, even though the PPO was completely deactivated. The optimum pH for the phenolic dehydrogenation in FWNS was about 7, and the alkaline condition was advantageous to the progress of the polymerization. Comprehensively, the maximum amount of dark spots was formed at about pH 9.Rationale Aging veterans often suffer from increased vulnerability, manifested among other things in old subjective age and poor perceived health. Though research has documented the contribution of trauma related variables to these negative appraisals, their associations with impostorism (i.e., the subjective experience that one is less adequate than others perceive) remain unexamined. Objective Filling this gap, this study explored the relations between impostorism and subjective age and perceived health among aging combat veterans. Method The study was conducted among 146 Israeli veterans of the 1973 Yom Kippur War. Participants were assessed for combat exposure, Posttraumatic Stress Disorder (PTSD) symptoms, and health-related behaviors during middle adulthood (1991; T1), and for subjective age, perceived health, impostorism, PTSD symptoms, and depressive symptoms during old age (2018; T2). Results The veterans' impostorism was associated with relatively old subjective age and poor perceived health, above and beyond the effects of age, health-related behaviors, combat exposure, depressive symptoms, and PTSD symptoms.
    The biochemical assays further revealed that the levels of total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) were reduced, while the activity of superoxide dismutase (SOD) was increased after apigenin treatment in hyperlipidemic rats. Moreover, we performed histopathological investigations and found that the lipidic deposition patterns were recovered and the amount of lipid vacuoles was significantly reduced in apigenin-treated hyperlipidemic rat liver. Western blotting assay showed that the expression of low-density lipoprotein receptor (LDLR) and lecithin-cholesterol acyltransferase (LCAT) were up-regulated in the apigenin-treated samples. Overall, our results demonstrated that the apigenin isolated from G. veitchiorum flower exhibited radical scavenging activities, and reversed the high fat diet-induced oxidative damage in rats. Its antioxidative activities are probably achieved via LDLR-LCAT signaling pathway.Biogenic amines are the important markers for food spoilage, thus, an on-package sensor for biogenic amine detection is crucial for food quality control. A dual detection platform including colorimetry and LDI-MS was developed for screening and quantitative determining of biogenic amines. Porous PLA film, was fabricated using calcium carbonate nanoparticles to enhance film porosity leading to increased surface area of colorimetric sensor. The color intensity significantly increases depending upon the enhanced analyte concentration with a linear range of 2.0-10.0 mg/mL for putrescine, and 0.1-6.0 mg/mL for cadaverine. On another layer, graphene oxide paper was applied as an LDI-MS substrate for sensitive quantification of biogenic amines. LOD values measured on graphene oxide coated side by LDI-MS were found to be 0.07 pM and 0.02 pM for putrescine and cadaverine, respectively. This platform was successfully applied for the detection of biogenic amines in pork samples with satisfactory results.The processing and digestive stability of ethanolic extracts from four Thai rice bran varieties, namely Khao Dawk Mali 105, Hom Nil, Kiaw Ngu, and Leum Pua, were assessed by applying different thermal and pH conditions, as well as in vitro gastrointestinal digestion models. High-performance liquid chromatography, Folin-Ciocalteu analysis, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) assays were used to determine the chemical composition, total phenolic content (TPC), and antioxidant activity. Thermal treatment at 100 °C for 15 min induced the degradation of phenolic components and TPC, whereas the antioxidant activities measured by DPPH and FRAP assays remained stable after the heat treatment. Higher phenolic content and antioxidant activity values were observed in the extracts incubated at acidic pH levels of 3 and 5. After simulated digestion, all extracts exhibited the decrease of phenolic compounds and anthocyanin contents, as well as antioxidant activities.It has been proven that at increased temperature, sterols can undergo various chemical reactions e.g., oxidation, dehydrogenation, dehydration and polymerisation. The objectives of this study are to prove the existence of dimers and to quantitatively analyse the dimers (3β,3'β-disteryl ethers). Sterol-rich samples were heated at 180 °C, 200 °C and 220 °C for 1 to 5 h. Quantitative analyses of the 3β,3'β-disteryl ethers were conducted using liquid extraction, solid-phase extraction and gas chromatography coupled with mass spectrometry. Additionally, for the analyses, suitable standards were synthetized from native sterols. To identify the mechanism of 3β,3'β-disteryl ether formation at high temperatures, an attempt was made to use the proposed synthesis method. Additionally, due to the association of sterols and sterol derivatives with atherosclerosis, preliminary studies with synthetized 3β,3'β-disteryl ethers on endothelial cells were conducted.Polysaccharides are a major active component of Porphyra haitanensis, which is an important food source in many countries. Four different molecular-weight fractions, namely PHPD-I (329 kDa), PHPD-II (203 kDa), PHPD-III (128 kDa), and PHPD-IV (10 kDa), were obtained from P. haitanensis polysaccharides by degradation using the H2O2/ascorbic acid system. PHPD-IV elicited the highest level of antioxidant and immunostimulatory activity among the four fractions. https://www.selleckchem.com/products/IC-87114.html PHPD-IV was purified by DEAE-cellulose column and five fractions were obtained, designated PHPD-IV-1-PHPD-IV-5. PHPD-IV-4 displayed the greatest biological activity by up-regulating the phosphorylation of MAPK signalling molecules. PHPD-IV-4 was further purified, and its structure was characterized by monosaccharide composition and 1/2D-NMR analysis. The result revealed that PHPD-IV-4 was repeated units of → 3) β-d-galactose (1 → 4) 3, 6-anhydro-α-l-galactose (1→, and → 3) β-d-galactose (1 → 4) α-l-galactose-6-S (1→. This study provides a theoretical basis for the utilisation and structure-activity assessment of P. haitanensis polysaccharides.The role of polyphenol oxidase (PPO) in the browning of fresh wet noodle sheets (FWNS) was discussed. To release the chemical formation mechanism of the dark spots formed on FWNS, the reconstituted FWNS and PPO-catechol reaction systems were prepared. Different from the overall color change of FWNS, almost all the melanins in dark spots were indirect products of PPO catalysis. The PPO catalytic dehydrogenation was an essential step for the formation of dark spots, but once the phenol dehydrogenation products were formed, the dark spots could still form through a further polymerization process, even though the PPO was completely deactivated. The optimum pH for the phenolic dehydrogenation in FWNS was about 7, and the alkaline condition was advantageous to the progress of the polymerization. Comprehensively, the maximum amount of dark spots was formed at about pH 9.Rationale Aging veterans often suffer from increased vulnerability, manifested among other things in old subjective age and poor perceived health. Though research has documented the contribution of trauma related variables to these negative appraisals, their associations with impostorism (i.e., the subjective experience that one is less adequate than others perceive) remain unexamined. Objective Filling this gap, this study explored the relations between impostorism and subjective age and perceived health among aging combat veterans. Method The study was conducted among 146 Israeli veterans of the 1973 Yom Kippur War. Participants were assessed for combat exposure, Posttraumatic Stress Disorder (PTSD) symptoms, and health-related behaviors during middle adulthood (1991; T1), and for subjective age, perceived health, impostorism, PTSD symptoms, and depressive symptoms during old age (2018; T2). Results The veterans' impostorism was associated with relatively old subjective age and poor perceived health, above and beyond the effects of age, health-related behaviors, combat exposure, depressive symptoms, and PTSD symptoms.
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  • BACKGROUND Conflict-related injuries sustained by civilians and local combatants are poorly described, unlike injuries sustained by US, North Atlantic Treaty Organization, and coalition military personnel. An understanding of injury epidemiology in twenty-first century armed conflict is required to plan humanitarian trauma systems capable of responding to population needs. METHODS We conducted a systematic search of databases (e.g., PubMed, Embase, Web of Science, World Health Organization Catalog, Google Scholar) and grey literature repositories to identify records that described conflict-related injuries sustained by civilians and local combatants since 2001. RESULTS The search returned 3501 records. 49 reports representing conflicts in 18 countries were included in the analysis and described injuries of 58,578 patients. 79.3% of patients were male, and 34.7% were under age 18 years. Blast injury was the predominant mechanism (50.2%), and extremities were the most common anatomic region of injury (33.5%). The heterogeneity and lack of reporting of data elements prevented pooled analysis and limited the generalizability of the results. For example, data elements including measures of injury severity, resource utilization (ventilator support, transfusion, surgery), and outcomes other than mortality (disability, quality of life measures) were presented by fewer than 25% of reports. CONCLUSIONS Data describing the needs of civilians and local combatants injured during conflict are currently inadequate to inform the development of humanitarian trauma systems. To guide system-wide capacity building and quality improvement, we advocate for a humanitarian trauma registry with a minimum set of data elements.BACKGROUND Intestinal volvulus is a common cause of mechanical intestinal obstruction (MIO) in Africa. Sigmoid volvulus has been well characterized in both high-income and low-income countries, but there is also a predilection for small bowel volvulus in sub-Saharan Africa. METHODS An analysis was performed of the Kamuzu Central Hospital Acute Care Surgery Registry from 2013 to 2019 on patients presenting with intestinal volvulus. Bivariate analysis was performed for covariates based on the intestinal volvulus type. Multivariate Poisson regression models estimated the relative risk of volvulus and mortality. RESULTS A total of 4352 patients were captured in the registry. Overall, 1037 patients (23.8%) were diagnosed with MIO. Intestinal volvulus accounted for 499 (48.1%) of patients with MIO. Sigmoid volvulus, midgut volvulus, ileosigmoid knotting, and cecal volvulus accounted for 57.7% (n = 288), 19.8% (n = 99), 20.8% (n = 104), and 1.6% (n = 8), respectively. Mean age was 46.8 years (SD 17.2) with a male preponderance (n = 429, 86.0%) and 14.8% (n = 74) mortality. Overall, the most common operations performed were large bowel (n = 326, 74.4%) and small bowel (n = 76, 16.7%) resections with 18.0% (n = 90) ostomy formation. Upon regression modeling, the relative risk for volvulus was 2.7 times higher in men than women after controlling for season and age. There was no statistically significant difference in the relative risk of mortality based on the type of volvulus. CONCLUSION Volvulus is a significant cause of primary bowel obstruction in sub-Saharan Africa. Type of intestinal volvulus is not associated increased risk of mortality. Reasons for increases in the incidence of small bowel volvulus are still largely undetermined.INTRODUCTION Secondary overtriage (OT) is the unnecessary transfer of injured patients between facilities. In low- and middle-income countries (LMICs), which shoulder the greatest burden of trauma globally, the impact of wasted resources on an overburdened system is high. This study determined the rate and associated characteristics of OT at a Malawian central hospital. METHODS A retrospective analysis of prospectively collected data from January 2012 through July 2017 was performed at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. https://www.selleckchem.com/products/Y-27632.html Patients were considered OT if they were discharged alive within 48 h without undergoing a procedure, and were not severely injured or in shock on arrival. Factors evaluated for association with OT included patient demographics, injury characteristics, and transferring facility information. RESULTS Of 80,915 KCH trauma patients, 15,422 (19.1%) transferred from another facility. Of these, 8703 (56.2%) were OT. OT patients were younger (median 15, IQR 6-31 versus median 26, IQR 11-38, p  less then  0.001). Patients with primary extremity injury (5308, 59.9%) were overtriaged more than those with head injury (1991, 51.8%) or torso trauma (1349, 50.8%), p  less then  0.001. The OT rate was lower at night (18.9% v 28.7%, p  less then  0.001) and similar on weekends (20.4% v 21.8%, p = 0.03). OT was highest for penetrating wounds, bites, and falls; burns were the lowest. In multivariable modeling, risk of OT was greatest for burns and soft tissue injuries. CONCLUSIONS The majority of trauma patients who transfer to KCH are overtriaged. Implementation of transfer criteria, trauma protocols, and interhospital communication can mitigate the strain of OT in resource-limited settings.BACKGROUND Right-sided colonic diverticulitis represents less than 5% of diverticulitis cases in North America. The purpose of this study was to describe the management and outcomes for patients with a first episode of right-sided diverticulitis in a North American center. METHODS This was a retrospective cohort study, including all patients managed for right-sided diverticulitis at a single tertiary-care institution from 2000 to 2017. Patient demographics, disease characteristics, and treatment strategies were described. Short- (emergency surgery, operative morbidity, treatment failure) and long-term (recurrence, elective operation) outcomes were reported. Patients with right-sided diverticulitis were then compared to a cohort of patients with left-sided diverticulitis. RESULTS Sixty-seven patients were managed for a first episode of right-sided diverticulitis, three (4.5%) of which were subsequently diagnosed with right-sided colon cancer; 64 patients therefore formed the population. Mean age was 51.2 ± 17.
    BACKGROUND Conflict-related injuries sustained by civilians and local combatants are poorly described, unlike injuries sustained by US, North Atlantic Treaty Organization, and coalition military personnel. An understanding of injury epidemiology in twenty-first century armed conflict is required to plan humanitarian trauma systems capable of responding to population needs. METHODS We conducted a systematic search of databases (e.g., PubMed, Embase, Web of Science, World Health Organization Catalog, Google Scholar) and grey literature repositories to identify records that described conflict-related injuries sustained by civilians and local combatants since 2001. RESULTS The search returned 3501 records. 49 reports representing conflicts in 18 countries were included in the analysis and described injuries of 58,578 patients. 79.3% of patients were male, and 34.7% were under age 18 years. Blast injury was the predominant mechanism (50.2%), and extremities were the most common anatomic region of injury (33.5%). The heterogeneity and lack of reporting of data elements prevented pooled analysis and limited the generalizability of the results. For example, data elements including measures of injury severity, resource utilization (ventilator support, transfusion, surgery), and outcomes other than mortality (disability, quality of life measures) were presented by fewer than 25% of reports. CONCLUSIONS Data describing the needs of civilians and local combatants injured during conflict are currently inadequate to inform the development of humanitarian trauma systems. To guide system-wide capacity building and quality improvement, we advocate for a humanitarian trauma registry with a minimum set of data elements.BACKGROUND Intestinal volvulus is a common cause of mechanical intestinal obstruction (MIO) in Africa. Sigmoid volvulus has been well characterized in both high-income and low-income countries, but there is also a predilection for small bowel volvulus in sub-Saharan Africa. METHODS An analysis was performed of the Kamuzu Central Hospital Acute Care Surgery Registry from 2013 to 2019 on patients presenting with intestinal volvulus. Bivariate analysis was performed for covariates based on the intestinal volvulus type. Multivariate Poisson regression models estimated the relative risk of volvulus and mortality. RESULTS A total of 4352 patients were captured in the registry. Overall, 1037 patients (23.8%) were diagnosed with MIO. Intestinal volvulus accounted for 499 (48.1%) of patients with MIO. Sigmoid volvulus, midgut volvulus, ileosigmoid knotting, and cecal volvulus accounted for 57.7% (n = 288), 19.8% (n = 99), 20.8% (n = 104), and 1.6% (n = 8), respectively. Mean age was 46.8 years (SD 17.2) with a male preponderance (n = 429, 86.0%) and 14.8% (n = 74) mortality. Overall, the most common operations performed were large bowel (n = 326, 74.4%) and small bowel (n = 76, 16.7%) resections with 18.0% (n = 90) ostomy formation. Upon regression modeling, the relative risk for volvulus was 2.7 times higher in men than women after controlling for season and age. There was no statistically significant difference in the relative risk of mortality based on the type of volvulus. CONCLUSION Volvulus is a significant cause of primary bowel obstruction in sub-Saharan Africa. Type of intestinal volvulus is not associated increased risk of mortality. Reasons for increases in the incidence of small bowel volvulus are still largely undetermined.INTRODUCTION Secondary overtriage (OT) is the unnecessary transfer of injured patients between facilities. In low- and middle-income countries (LMICs), which shoulder the greatest burden of trauma globally, the impact of wasted resources on an overburdened system is high. This study determined the rate and associated characteristics of OT at a Malawian central hospital. METHODS A retrospective analysis of prospectively collected data from January 2012 through July 2017 was performed at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. https://www.selleckchem.com/products/Y-27632.html Patients were considered OT if they were discharged alive within 48 h without undergoing a procedure, and were not severely injured or in shock on arrival. Factors evaluated for association with OT included patient demographics, injury characteristics, and transferring facility information. RESULTS Of 80,915 KCH trauma patients, 15,422 (19.1%) transferred from another facility. Of these, 8703 (56.2%) were OT. OT patients were younger (median 15, IQR 6-31 versus median 26, IQR 11-38, p  less then  0.001). Patients with primary extremity injury (5308, 59.9%) were overtriaged more than those with head injury (1991, 51.8%) or torso trauma (1349, 50.8%), p  less then  0.001. The OT rate was lower at night (18.9% v 28.7%, p  less then  0.001) and similar on weekends (20.4% v 21.8%, p = 0.03). OT was highest for penetrating wounds, bites, and falls; burns were the lowest. In multivariable modeling, risk of OT was greatest for burns and soft tissue injuries. CONCLUSIONS The majority of trauma patients who transfer to KCH are overtriaged. Implementation of transfer criteria, trauma protocols, and interhospital communication can mitigate the strain of OT in resource-limited settings.BACKGROUND Right-sided colonic diverticulitis represents less than 5% of diverticulitis cases in North America. The purpose of this study was to describe the management and outcomes for patients with a first episode of right-sided diverticulitis in a North American center. METHODS This was a retrospective cohort study, including all patients managed for right-sided diverticulitis at a single tertiary-care institution from 2000 to 2017. Patient demographics, disease characteristics, and treatment strategies were described. Short- (emergency surgery, operative morbidity, treatment failure) and long-term (recurrence, elective operation) outcomes were reported. Patients with right-sided diverticulitis were then compared to a cohort of patients with left-sided diverticulitis. RESULTS Sixty-seven patients were managed for a first episode of right-sided diverticulitis, three (4.5%) of which were subsequently diagnosed with right-sided colon cancer; 64 patients therefore formed the population. Mean age was 51.2 ± 17.
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  • 431, moderate agreement) compared to SD-CT (k = 0.209, fair agreement). Almost all VS-CT series had false positive findings (97-99 out of 100). Average reading time was significantly shorter in the VS-CT compared to the SD-CT (154 ± 134vs. 194 ± 126; 21%, p less then 0.001). CONCLUSIONS Vessel suppression increases nodule detection rate, improves interreader agreement, and reduces reading time in chest CT of oncologic patients. Due to false positive results a consensus reading with the SD-CT is essential. BACKGROUND Lipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS). METHODS The Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available. RESULTS The patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. https://www.selleckchem.com/products/bay-069.html 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (-6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test). CONCLUSIONS Lp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients. BACKGROUND It has been shown that most paroxysmal atrial fibrillation (AF) can be terminated by pulmonary vein (PV) isolation alone, suggesting that rapid discharges from PV drive AF. To define the driving mechanism of AF, we compared the activation sequence in the body of left atrium (LA) to that within PV. METHODS Endocardial noncontact mapping of LA body (LA group; n = 16) and selective endocardial mapping of left superior PV (LSPV) (PV group; n = 13) were performed in 29 paroxysmal AF patients. The frequency of pivoting activation, wave breakup, and wave fusion observed in LA were compared to those in LSPV to define the driving mechanism of AF. Circumferential ablation lesion around left PV was performed after right PV isolation to examine the effect of linear lesion around PV on AF termination both in LA and PV groups. RESULTS The frequency of pivoting activation, wave breakup, and wave fusion in PV group were significantly higher than those in LA group (36.5 ± 17.7 vs 5.0 ± 2.2 times/seconds, p  less then  0.001, 10.1 ± 4.3 vs 5.0 ± 2.2 times/seconds, p = 0.004, 18.1 ± 5.7 vs 11.0 ± 5.2, p = 0.002). Especially in the PV group, the frequency of pivoting activation was significantly higher than that of wave breakup and wave fusion (36.5 ± 17.7 vs 10.1 ± 4.3 times/seconds, p  less then  0.001, 36.5 ± 17.7 vs 18.1 ± 5.7 times/seconds, p  less then  0.001). These disorganized activations in LSPV were eliminated by the circumferential ablation lesion around left PV (pivoting activation; 36.5 ± 17.7 vs 9.3 ± 2.3 times/seconds, p  less then  0.001, wave breakup; 10.1±1.3 times/seconds, p = 0.003, wave fusion; 18.1 ± 5.7 vs 5.7 ± 1.8, p  less then  0.001), resulted in AF termination in all patients in both LA and PV groups. CONCLUSIONS Activation sequence within PV was more disorganized than that in LA body. Frequent episodes of pivoting activation rather than wave breakup and fusion observed within PV acted as the driving sources of paroxysmal AF. BACKGROUND We investigated the effect of inter-arm blood pressure differences (IABPD) on the percutaneous coronary intervention (PCI) outcomes of patients with coronary artery diseases. METHODS We retrospectively reviewed the data of blood pressures measured simultaneously in the bilateral arms of 855 patients (560 males) who underwent PCI with drug-eluting stents for coronary artery diseases. IABPD was defined as the difference of blood pressure in both arms. The primary outcome was the presence of major adverse cardiac events (****) consisting of cardiovascular death, myocardial infarction, stroke, and ischemia-driven target vessel revascularization. RESULTS The mean age of the included patients was 66.2 ± 11.6 years, with a mean follow-up period of 44.5 ± 26.4 months. **** occurred in 15.2% of patients, showing a higher rate in the higher IABPD group (≥10 mmHg) than in the lower IABPD group ( less then 10 mmHg) (22.5% vs 14.5%, p = 0.081). The difference was induced by a higher rate of ischemia-driven target vessel revascularization (17.5% vs 8.3%, p = 0.011). The Kaplan-Meier survival analysis revealed a greater incidence of **** in patients with a higher IABPD (log rank p = 0.054). The Cox proportional hazard analysis showed that IABPD was an independent predictor of long-term **** (hazard ratio, 1.028; 95% confidence interval, 1.002-1.055; p = 0.037), along with age, diabetes mellitus, and number of implanted stents. CONCLUSION Among patients treated with PCI, the incidence of **** was significantly higher in those with a higher IABPD (≥10 mmHg) than in those with a lower IABPD ( less then 10 mmHg), which was mainly driven by ischemia-driven target vessel revascularization. BACKGROUND The incidence of cardiac implantable electronic device (CIED) infection is increasing worldwide. However, data regarding this phenomenon in Japan and information on factors associated with developing CIED infection are limited. Our aim was to compare the incidence of CIED infection between pre-current (past 10-20 years) and current (past 10 years) clinical settings and to investigate risk factors for CIED infection in current clinical settings in a Japanese population. METHODS This observational study included 1749 patients (age 77 ± 12 years, 824 males) who underwent a CIED-related procedure between August 1999 and July 2019 at our institution. We defined the pre-current and current clinical setting periods as August 1999-July 2009 (period I) and August 2009-July 2019 (period II), respectively. We compared the incidence rate of CIED infection between periods and evaluated the risk factors for CIED infection in period II by multivariate analysis. RESULTS A CIED infection was identified in 0.7% (5/709 patients) and 1.
    431, moderate agreement) compared to SD-CT (k = 0.209, fair agreement). Almost all VS-CT series had false positive findings (97-99 out of 100). Average reading time was significantly shorter in the VS-CT compared to the SD-CT (154 ± 134vs. 194 ± 126; 21%, p less then 0.001). CONCLUSIONS Vessel suppression increases nodule detection rate, improves interreader agreement, and reduces reading time in chest CT of oncologic patients. Due to false positive results a consensus reading with the SD-CT is essential. BACKGROUND Lipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS). METHODS The Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available. RESULTS The patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. https://www.selleckchem.com/products/bay-069.html 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (-6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test). CONCLUSIONS Lp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients. BACKGROUND It has been shown that most paroxysmal atrial fibrillation (AF) can be terminated by pulmonary vein (PV) isolation alone, suggesting that rapid discharges from PV drive AF. To define the driving mechanism of AF, we compared the activation sequence in the body of left atrium (LA) to that within PV. METHODS Endocardial noncontact mapping of LA body (LA group; n = 16) and selective endocardial mapping of left superior PV (LSPV) (PV group; n = 13) were performed in 29 paroxysmal AF patients. The frequency of pivoting activation, wave breakup, and wave fusion observed in LA were compared to those in LSPV to define the driving mechanism of AF. Circumferential ablation lesion around left PV was performed after right PV isolation to examine the effect of linear lesion around PV on AF termination both in LA and PV groups. RESULTS The frequency of pivoting activation, wave breakup, and wave fusion in PV group were significantly higher than those in LA group (36.5 ± 17.7 vs 5.0 ± 2.2 times/seconds, p  less then  0.001, 10.1 ± 4.3 vs 5.0 ± 2.2 times/seconds, p = 0.004, 18.1 ± 5.7 vs 11.0 ± 5.2, p = 0.002). Especially in the PV group, the frequency of pivoting activation was significantly higher than that of wave breakup and wave fusion (36.5 ± 17.7 vs 10.1 ± 4.3 times/seconds, p  less then  0.001, 36.5 ± 17.7 vs 18.1 ± 5.7 times/seconds, p  less then  0.001). These disorganized activations in LSPV were eliminated by the circumferential ablation lesion around left PV (pivoting activation; 36.5 ± 17.7 vs 9.3 ± 2.3 times/seconds, p  less then  0.001, wave breakup; 10.1±1.3 times/seconds, p = 0.003, wave fusion; 18.1 ± 5.7 vs 5.7 ± 1.8, p  less then  0.001), resulted in AF termination in all patients in both LA and PV groups. CONCLUSIONS Activation sequence within PV was more disorganized than that in LA body. Frequent episodes of pivoting activation rather than wave breakup and fusion observed within PV acted as the driving sources of paroxysmal AF. BACKGROUND We investigated the effect of inter-arm blood pressure differences (IABPD) on the percutaneous coronary intervention (PCI) outcomes of patients with coronary artery diseases. METHODS We retrospectively reviewed the data of blood pressures measured simultaneously in the bilateral arms of 855 patients (560 males) who underwent PCI with drug-eluting stents for coronary artery diseases. IABPD was defined as the difference of blood pressure in both arms. The primary outcome was the presence of major adverse cardiac events (MACE) consisting of cardiovascular death, myocardial infarction, stroke, and ischemia-driven target vessel revascularization. RESULTS The mean age of the included patients was 66.2 ± 11.6 years, with a mean follow-up period of 44.5 ± 26.4 months. MACE occurred in 15.2% of patients, showing a higher rate in the higher IABPD group (≥10 mmHg) than in the lower IABPD group ( less then 10 mmHg) (22.5% vs 14.5%, p = 0.081). The difference was induced by a higher rate of ischemia-driven target vessel revascularization (17.5% vs 8.3%, p = 0.011). The Kaplan-Meier survival analysis revealed a greater incidence of MACE in patients with a higher IABPD (log rank p = 0.054). The Cox proportional hazard analysis showed that IABPD was an independent predictor of long-term MACE (hazard ratio, 1.028; 95% confidence interval, 1.002-1.055; p = 0.037), along with age, diabetes mellitus, and number of implanted stents. CONCLUSION Among patients treated with PCI, the incidence of MACE was significantly higher in those with a higher IABPD (≥10 mmHg) than in those with a lower IABPD ( less then 10 mmHg), which was mainly driven by ischemia-driven target vessel revascularization. BACKGROUND The incidence of cardiac implantable electronic device (CIED) infection is increasing worldwide. However, data regarding this phenomenon in Japan and information on factors associated with developing CIED infection are limited. Our aim was to compare the incidence of CIED infection between pre-current (past 10-20 years) and current (past 10 years) clinical settings and to investigate risk factors for CIED infection in current clinical settings in a Japanese population. METHODS This observational study included 1749 patients (age 77 ± 12 years, 824 males) who underwent a CIED-related procedure between August 1999 and July 2019 at our institution. We defined the pre-current and current clinical setting periods as August 1999-July 2009 (period I) and August 2009-July 2019 (period II), respectively. We compared the incidence rate of CIED infection between periods and evaluated the risk factors for CIED infection in period II by multivariate analysis. RESULTS A CIED infection was identified in 0.7% (5/709 patients) and 1.
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  • The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. https://www.selleckchem.com/products/beta-glycerophosphate-sodium-salt-hydrate.html Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239 SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c ****) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected **** were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in **** and subsequently treated with synthesized RU-S4.This study investigated physical activity (PA) and sedentary time (SED) in relation to hippocampal gray matter volume (GMV) in pediatric overweight/obesity. Ninety-three children (10 ± 1 year) were classified as overweight, obesity type I, or type II-III. PA was assessed with non-dominant wrist accelerometers. GMV was acquired by magnetic resonance imaging (MRI). Neither PA nor SED associated with GMV in the hippocampus in the whole sample (p > 0.05). However, we found some evidence of moderation by weight status (p less then 0.150). Moderate-to-vigorous PA (MVPA) positively associated with GMV in the right hippocampus in obesity type I (B = 5.62, p = 0.017), which remained when considering SED, light PA, and sleep using compositional data (γ = 375.3, p = 0.04). Compositional models also depicted a negative association of SED relative to the remaining behaviors with GMV in the right hippocampus in overweight (γ = -1838.4, p = 0.038). Reallocating 20 min/day of SED to MVPA was associated with 100 mm3 GMV in the right hippocampus in obesity type I. Multivariate pattern analysis showed a negative-to-positive association pattern between PA of increasing intensity and GMV in the right hippocampus in obesity type II-III. Our findings support that reducing SED and increasing MVPA are associated with greater GMV in the right hippocampus in pediatric overweight/obesity. Further studies should corroborate our findings.The major defense system against microbial pathogens in vertebrates is the adaptive immune response and represents an effective mechanism in cancer surveillance. T cells represent an essential component of this complex system. They can recognize myriads of antigens as short peptides (p) originated from the intracellular degradation of foreign proteins presented by major histocompatibility complex (MHC) proteins. The clonotypic T-cell antigen receptor (TCR) is specialized in recognizing pMHC and triggering T cells immune response. It is still unclear how TCR engagement to pMHC is translated into the intracellular signal that initiates T-cell immune response. Some work has suggested the possibility that pMHC binding induces in the TCR conformational changes transmitted to its companion CD3 subunits that govern signaling. The conformational changes would promote phosphorylation of the CD3 complex ζ chain that initiates signal propagation intracellularly. Here, we used all-atom molecular dynamics simulations (MDs) of 500 ns to analyze the conformational behavior of three TCRs (1G4, ILA1 and ILA1α1β1) interacting with the same ****class I (HLA-A*0201) bound to different peptides, and modelled in the presence of a lipid bilayer. Our data suggest a correlation between the conformations explored by the β-chain constant regions and the T-cell response experimentally determined. In particular, independently by the TCR type involved in the interaction, the TCR activation seems to be linked to a specific zone of the conformational space explored by the β-chain constant region. Moreover, TCR ligation restricts the conformational space the ****class I groove.Mobile health technologies are being developed for personal lifestyle and medical healthcare support, of which a growing number are designed to assist smokers to quit. The potential impact of these technologies in the fight against smoking addiction and on improving quitting rates must be systematically evaluated. The aim of this report is to identify and appraise the most promising smoking detection and quitting technologies (e.g., smartphone apps, wearable devices) supporting smoking reduction or quitting programs. We searched PubMed and Scopus databases (2008-2019) for studies on mobile health technologies developed to assist smokers to quit using a combination of Medical Subject Headings topics and free text terms. A Google search was also performed to retrieve the most relevant smartphone apps for quitting smoking, considering the average user's rating and the ranking computed by the search engine algorithms. All included studies were evaluated using consolidated criteria for reporting qualitative researeal-life daily scenarios.The study was an initial exploration of the current ototoxicity assessment and management practices by audiologists in South Africa. An exploratory survey research methodology through a cross-sectional research design was adopted where audiologists were recruited from professional associations' databases in South Africa, using specific inclusion criteria. The study made use of an 18-item web-based survey guided by the Health Professions Council of South Africa (HPCSA) (2018) guidelines which were developed from reviewing international guidelines such as the American Speech-Language-Hearing Association (ASHA,1994) and the American Academy of Audiology (AAA, 2009). The study surveyed 31 audiologists from across the country. Data were analyzed through descriptive statistics. Findings implied significant gaps between knowledge and translation of this knowledge into practice. Over two thirds of the participants engage with ototoxicity monitoring and management, but the practices adopted by them do not align with international standards nor with the national HPCSA guidelines on assessment and management of patients on ototoxic medications.
    The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. https://www.selleckchem.com/products/beta-glycerophosphate-sodium-salt-hydrate.html Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239 SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c mice) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected mice were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in mice and subsequently treated with synthesized RU-S4.This study investigated physical activity (PA) and sedentary time (SED) in relation to hippocampal gray matter volume (GMV) in pediatric overweight/obesity. Ninety-three children (10 ± 1 year) were classified as overweight, obesity type I, or type II-III. PA was assessed with non-dominant wrist accelerometers. GMV was acquired by magnetic resonance imaging (MRI). Neither PA nor SED associated with GMV in the hippocampus in the whole sample (p > 0.05). However, we found some evidence of moderation by weight status (p less then 0.150). Moderate-to-vigorous PA (MVPA) positively associated with GMV in the right hippocampus in obesity type I (B = 5.62, p = 0.017), which remained when considering SED, light PA, and sleep using compositional data (γ = 375.3, p = 0.04). Compositional models also depicted a negative association of SED relative to the remaining behaviors with GMV in the right hippocampus in overweight (γ = -1838.4, p = 0.038). Reallocating 20 min/day of SED to MVPA was associated with 100 mm3 GMV in the right hippocampus in obesity type I. Multivariate pattern analysis showed a negative-to-positive association pattern between PA of increasing intensity and GMV in the right hippocampus in obesity type II-III. Our findings support that reducing SED and increasing MVPA are associated with greater GMV in the right hippocampus in pediatric overweight/obesity. Further studies should corroborate our findings.The major defense system against microbial pathogens in vertebrates is the adaptive immune response and represents an effective mechanism in cancer surveillance. T cells represent an essential component of this complex system. They can recognize myriads of antigens as short peptides (p) originated from the intracellular degradation of foreign proteins presented by major histocompatibility complex (MHC) proteins. The clonotypic T-cell antigen receptor (TCR) is specialized in recognizing pMHC and triggering T cells immune response. It is still unclear how TCR engagement to pMHC is translated into the intracellular signal that initiates T-cell immune response. Some work has suggested the possibility that pMHC binding induces in the TCR conformational changes transmitted to its companion CD3 subunits that govern signaling. The conformational changes would promote phosphorylation of the CD3 complex ζ chain that initiates signal propagation intracellularly. Here, we used all-atom molecular dynamics simulations (MDs) of 500 ns to analyze the conformational behavior of three TCRs (1G4, ILA1 and ILA1α1β1) interacting with the same MHC class I (HLA-A*0201) bound to different peptides, and modelled in the presence of a lipid bilayer. Our data suggest a correlation between the conformations explored by the β-chain constant regions and the T-cell response experimentally determined. In particular, independently by the TCR type involved in the interaction, the TCR activation seems to be linked to a specific zone of the conformational space explored by the β-chain constant region. Moreover, TCR ligation restricts the conformational space the MHC class I groove.Mobile health technologies are being developed for personal lifestyle and medical healthcare support, of which a growing number are designed to assist smokers to quit. The potential impact of these technologies in the fight against smoking addiction and on improving quitting rates must be systematically evaluated. The aim of this report is to identify and appraise the most promising smoking detection and quitting technologies (e.g., smartphone apps, wearable devices) supporting smoking reduction or quitting programs. We searched PubMed and Scopus databases (2008-2019) for studies on mobile health technologies developed to assist smokers to quit using a combination of Medical Subject Headings topics and free text terms. A Google search was also performed to retrieve the most relevant smartphone apps for quitting smoking, considering the average user's rating and the ranking computed by the search engine algorithms. All included studies were evaluated using consolidated criteria for reporting qualitative researeal-life daily scenarios.The study was an initial exploration of the current ototoxicity assessment and management practices by audiologists in South Africa. An exploratory survey research methodology through a cross-sectional research design was adopted where audiologists were recruited from professional associations' databases in South Africa, using specific inclusion criteria. The study made use of an 18-item web-based survey guided by the Health Professions Council of South Africa (HPCSA) (2018) guidelines which were developed from reviewing international guidelines such as the American Speech-Language-Hearing Association (ASHA,1994) and the American Academy of Audiology (AAA, 2009). The study surveyed 31 audiologists from across the country. Data were analyzed through descriptive statistics. Findings implied significant gaps between knowledge and translation of this knowledge into practice. Over two thirds of the participants engage with ototoxicity monitoring and management, but the practices adopted by them do not align with international standards nor with the national HPCSA guidelines on assessment and management of patients on ototoxic medications.
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