Associations between dietary diversity and high sensitive C-reactive protein among Japanese workers: findings of a cross-sectional and longitudinal study.

PURPOSE: To clarify the association between dietary diversity and inflammatory status in Japanese workers. METHODS: Of 1,460 men and women aged 20-64 years in 2010 (baseline), those who were followed-up at least once between 2011 and 2018 were included in this study; 1,433 participants and 745 participants were included in the cross-sectional and longitudinal analyses, respectively. Dietary intake was assessed using a food frequency questionnaire at baseline, and the dietary diversity score was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). High-sensitivity C-reactive protein (hs-CRP) was taken to indicate inflammatory status at the baseline and follow-up surveys. In the cross-sectional analysis using baseline data, a generalized linear model was used to calculate adjusted means and 95% confidence intervals (CIs) for hs-CRP according to the QUANTIDD score. In the longitudinal analysis, generalized estimating equations were used to calculate the adjusted mean (95% CI) for hs-CRP in follow-up according to the QUANTIDD score at baseline. RESULTS: In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups. CONCLUSION: These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Applying a modified systematic review and integrated assessment framework (SYRINA) - a case study on triphenyl phosphate.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development.

Over the past decade, the therapeutic potential of nanomaterials as novel drug delivery systems complementing conventional pharmacology has been widely acknowledged. Among these nanomaterials, lipid-based nanoparticles (LNPs) have shown remarkable pharmacological performance and promising therapeutic outcomes, thus gaining substantial interest in preclinical and clinical research. In this review, we introduce the main types of LNPs used in drug formulations such as liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and lipid polymer hybrid nanoparticles, focusing on their main physicochemical properties and therapeutic potential. We discuss computational studies and modeling techniques to enhance the understanding of how LNPs interact with therapeutic cargo and to predict the potential effectiveness of such interactions in therapeutic applications. We also analyze the benefits and drawbacks of various LNP production techniques such as nanoprecipitation, emulsification, evaporation, thin film hydration, microfluidic-based methods, and an impingement jet mixer. Additionally, we discuss the major challenges associated with industrial development, including stability and sterilization, storage, regulatory compliance, reproducibility, and quality control. Overcoming these challenges and facilitating regulatory compliance represent the key steps toward LNP's successful commercialization and translation into clinical settings.

Genetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiomyocyte loss following myocardial infarction cannot be addressed with current clinical therapies. Cell therapy with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a potential approach to replace cardiomyocyte loss. However, engraftment rates in pre-clinical studies have been low, highlighting a need to refine current iPSC-CM technology. In this study, we demonstrated that inducing Yes-associated protein (YAP) by genetic and pharmacological approaches resulted in increased iPSC-CM proliferation and reduced apoptosis in response to oxidative stress. Interestingly, iPSC-CM maturation was differently affected by each strategy, with genetic activation of YAP resulting in a more immature cardiomyocyte-like phenotype not witnessed upon pharmacological YAP activation. Overall, we conclude that YAP activation in iPSC-CMs enhances cell survival and proliferative capacity. Therefore, strategies targeting YAP, or its upstream regulator the Hippo signalling pathway, could potentially be used to improve the efficacy of iPSC-CM technology for use as a future regenerative therapy in myocardial infarction.

Creation of Single Vacancies in hBN with Electron Irradiation.

Understanding electron irradiation effects is vital not only for reliable transmission electron microscopy characterization, but increasingly also for the controlled manipulation of 2D materials. The displacement cross sections of monolayer hexagonal boron nitride (hBN) are measured using aberration-corrected scanning transmission electron microscopy in near ultra-high vacuum at primary beam energies between 50 and 90 keV. Damage rates below 80 keV are up to three orders of magnitude lower than previously measured at edges under poorer residual vacuum conditions, where chemical etching appears to dominate. Notably, it is possible to create single vacancies in hBN using electron irradiation, with boron almost twice as likely as nitrogen to be ejected below 80 keV. Moreover, any damage at such low energies cannot be explained by elastic knock-on, even when accounting for the vibrations of the atoms. A theoretical description is developed to account for the lowering of the displacement threshold due to valence ionization resulting from inelastic scattering of probe electrons, modeled using charge-constrained density functional theory molecular dynamics. Although significant reductions are found depending on the constrained charge, quantitative predictions for realistic ionization states are currently not possible. Nonetheless, there is potential for defect-engineering of hBN at the level of single vacancies using electron irradiation.

Micro RNA-411 Expression Improves Cardiac Phenotype Following Myocardial Infarction in Mice.

Induction of endogenous regenerative capacity has emerged as one promising approach to repair damaged hearts following myocardial infarction (MI). Re-expression of factors that are exclusively expressed during embryonic development may reactivate the ability of adult cardiomyocytes to regenerate. Here, we identified miR-411 as a potent inducer of cardiomyocyte proliferation. Overexpression of miR-411 in the heart significantly increased cardiomyocyte proliferation and survival in a model MI. We found that miR-411 enhances the activity of YAP, the main downstream effector of the Hippo pathway, in cardiomyocytes. In conclusion, miR-411 induces cardiomyocyte regeneration and improves cardiac function post-MI likely by modulating the Hippo/YAP pathway.

Do patients want clinicians to ask about social needs and include this information in their medical record?

BACKGROUND: Social needs screening in primary care may be valuable for addressing non-medical health-related factors, such as housing insecurity, that interfere with optimal medical care. Yet it is unclear if patients welcome such screening and how comfortable they are having this information included in electronic health records (EHR). OBJECTIVE: To assess patient attitudes toward inclusion of social needs information in the EHR and key correlates, such as sociodemographic status, self-rated health, and trust in health care. DESIGN, PARTICIPANTS, AND MAIN MEASURES: In a cross-sectional survey of patients attending a primary care clinic for annual or employment exams, 218/560 (38%) consented and completed a web survey or personal interview between 8/20/20-8/23/21. Patients provided social needs information using the Accountable Care Communities Screening Tool. For the primary outcome, patients were asked, "Would you be comfortable having these kinds of needs included in your health record (also known as your medical record or chart)?" ANALYSES: Regression models were estimated to assess correlates of patient comfort with including social needs information in medical records. KEY RESULTS: The median age was 45, 68.8% were female, and 78% were white. Median income was $75,000 and 84% reported education beyond high school. 85% of patients reported they were very or somewhat comfortable with questions about social needs, including patients reporting social needs. Social need ranged from 5.5% (utilities) to 26.6% (housing), and nonwhite and gender-nonconforming patients reported greater need. 20% reported "some" or "complete" discomfort with social needs information included in the EHR. Adjusting for age, gender, race, education, trust, and self-rated health, each additional reported social need significantly increased discomfort with the EHR for documenting social needs. CONCLUSIONS: People with greater social needs were more wary of having this information placed in the EHR. This is a concerning finding, since one rationale for collecting social need data is to use this information (presumably in the EHR) for addressing needs.

Wernicke-Korsakoff Syndrome in a Hunger Striker Despite Oral Thiamine Supplementation.

Case: We present the case of a 49-year-old woman who underwent a 237-day hunger strike on the streets of Pittsburgh, Pennsylvania. Despite medical supervision and appropriate micronutrient supplementation, including higher-than-recommended dosing of oral thiamine, the patient developed Wernicke's Encephalopathy and subsequent Korsakoff Syndrome. She is now permanently impaired. Introduction: Hunger strikers are subject to numerous sequelae of micronutrient deficiency. Among these are the paired conditions of Wernicke's Encephalopathy and Korsakoff Syndrome, conditions secondary to prolonged thiamine deficiency. Unfortunately, few published guidelines exist regarding the medical management of hunger strikers. Preventative dosing guidance is borrowed from what is recommended for prolonged malnourishment from eating disorders or chronic alcohol use. Available guidelines are rarely academic. Rather, they were created by governmental agencies for the management of hunger strikers in prison or similar states of detention or incarceration. There is an indirect body of evidence that oral thiamine supplementation is rarely protective against the sequelae of thiamine deficiency in hunger strikers. We discuss supplementation recommendations and the evidence for their failure in practice. We briefly explore the historical evidence for the anatomic and physiologic changes of prolonged starvation that potentially explain this treatment failure, and offer alternatives to standard supplementation. Conclusion: The current recommendations of the management of hunger strikers regarding the prevention of thiamine deficiency are inadequate, and rarely prevent the clinical sequelae. Alternate management strategies need to be both researched and empirically used, while that research is being carried out. Novel lipid-soluble thiamine derivatives have promise, but prophylactic intravenous/intramuscular thiamine should be explored as the current standard of care.

The Structural Analysis: Incorporating Structurally Competent Clinical Reasoning into Case-Based Presentations.

Structural and social determinants of health account for the health disparities we see along social hierarchies, and their impact has been made more evident by the recent COVID-19 pandemic. There have been increasing calls to incorporate structural competency into medical education. The structural and social context, however, has yet to be fully integrated into everyday clinical practice and little has been published on how to concretely imbed structural competency into clinical reasoning. The authors provide a framework for structural analysis, which incorporates four key steps: (1) developing a prioritized clinical problem list, (2) identifying social and structural root causes for clinical problems, (3) constructing and documenting a prioritized structural problem list, and (4) brainstorming solutions to address structural barriers and social needs. They show how structural analysis can be used to operationalize structural reasoning into everyday inpatient and outpatient clinical assessments.

Mental Health Problems Among Front-Line Healthcare Workers Caring for COVID-19 Patients in Vietnam: A Mixed Methods Study.

Aim: Healthcare workers have directly provided care for COVID-19 patients, and have faced many additional sources leading to poor mental health. The study aimed to investigate the mental health problems and related factors among healthcare staff in Vietnam. Methods: A descriptive cross-sectional mixed methods study, combining quantitative and qualitative research methods, was performed among 400 healthcare workers working at the National Hospital for Tropical Diseases and Ninh Binh General Hospital from the first day of treatment for COVID-19 patients to May 01, 2020. Results: The results showed that 8.0% of participants had stress, 17.5% of participants had anxiety, and 14.8% of participants had depression. Approximately 50% of participants reported that they had at least one of these symptoms. The findings illustrated that stress, anxiety, and depression were associated with the position in a hospital, health status during the COVID-19 pandemic, family members/relatives infected with COVID-19, physical and mental support from friends, family, and community, department, years of working, and the average work hours per day of healthcare workers exposed to COVID-19. Conclusion: During the COVID-19 pandemic, healthcare workers who worked in the hospital providing treatment and care for COVID-19 patients dealt with mental health problems such as stress, anxiety, and depression. It is necessary to promote mental health among healthcare workers, to contribute to the fight against the COVID-19 outbreak in Vietnam.

Identifying toggle genes from transcriptome-wide scatter: A new perspective for biological regulation.

The study of gene expression variability, especially for cancer and cell differentiation studies, has become important. Here, we investigate transcriptome-wide scatter of 23 cell types and conditions across different levels of biological complexity. We focused on genes that act like toggle switches between pairwise replicates of the same cell type, i.e. genes expressed in one replicate and not expressed in the other, sometimes also referred as ON/OFF genes. The proportion of these toggle genes dramatically increases from unicellular to multicellular organization, especially for development and cancer cells. A relevant portion of toggle switches are non-coding genes: in unicellular systems the most represented classes are tRNA and rRNA, while multicellular systems more frequently show lncRNA, sncRNA and pseudogenes. Notably, disease associated microRNAs (miRNAs), pseudogenes and numerous uncharacterized transcripts are present in both development and cancer cells. On top of the known intrinsic and extrinsic factors, our work indicates toggle genes as a novel collective component creating transcriptome-wide variability. This requires further investigation for elucidating both evolutionary and disease processes.

Impact of Point-of-Care Ultrasound in Medical Decision Making: Informing the Development of an Internal Medicine Global Health POCUS Curriculum.

BACKGROUND: Point-of-care Ultrasound (POCUS) is particularly useful in low-middle income countries (LMICs) where advanced imaging modalities and diagnostics are often unavailable. However, its use among Internal Medicine (IM) practitioners is limited and without standard curricula. This study describes POCUS scans performed by U.S. IM residents rotating in LMICs to provide recommendations for curriculum development. METHODS: IM residents within a global health track performed clinically-indicated POCUS scans at two sites. They logged their interpretations and whether or not the scan changed diagnosis or management. Scans were quality-assured by POCUS experts in the US to validate results. Using the criteria of prevalence, ease of learning, and impact, a framework was developed for a POCUS curriculum for IM practitioners within LMICs. RESULTS: A total of 256 studies were included in analysis. 237 (92.5%) answered the clinical question, 107 (41.8%) changed the diagnosis, and 106 (41.4%) changed management. The most frequently used applications were the Focused Assessment for Sonography for HIV associated TB (FASH) exam, finding fluid (pericardial effusion, pleural effusion, ascites), qualitative assessment of left ventricular function, and assessment for A-lines/B-lines/consolidation. The following scans met ease of learning criteria: FASH-basic, assessment of LV function, A-lines vs. B-lines, and finding fluid. Finding fluid and assessment of LV function changed diagnosis and management most frequently, greater than 50% of the time for each category. DISCUSSION/CONCLUSION: We recommend the following applications as highest yield for inclusion in a POCUS curriculum for IM practitioners within LMICs: finding fluid (pericardial effusion, pleural effusion, ascites) and assessment of gross LV function.

Trends in Internet Safety Education by Healthcare Providers.

INTRODUCTION: The purpose of this study was to explore healthcare provider training, comfort, and provision of internet safety counseling. Prior research has demonstrated increased parental concern regarding the pervasive access to the internet by children, including the potential impacts of risky internet behavior and adverse media exposure. METHODS: A self-reported survey was provided to a convenience sample of 31 healthcare providers during a mental health training seminar. Responses were analyzed using descriptive statistics. RESULTS: Internet safety counseling, especially regarding risky online behavior, was not a focal point of provider-patient interaction in the sample population. This finding was reinforced with more than half of the respondents indicating that they infrequently or never provide internet safety counseling (n = 17, 56%). While research has placed an emphasis on the importance of discussing the risks of exposure to violence, drugs, and sexually explicit media online, this study found that the topics most often discussed were setting time limits (77%), limiting access to media devices (67%), and supervising internet use (50%). This may be due in part to the fact that most respondents (n = 17, 57%) reported never receiving training on internet safety counseling. CONCLUSIONS: Overall, significant deficits were identified in internet safety counseling training for professionals and provision of education for families. These finding were inconsistent with the American Academy of Pediatrics recommendations around media use counseling and a point of urgent concern given the increasing time spent on media devices, particularly during the COVID pandemic.

Evaluation of diabetic peer support in Malawi.

Background: Type 2 diabetes is a major health concern worldwide and requires urgent attention from health care providers and policy makers. Due to shortage of health care workers in low-income countries, peer support programs have been viewed as a viable option in management of diabetes and have shown to be effective in sub-Saharan Africa. Objective: The aim of this study is to assess and evaluate the Kamuzu Central Hospital (KCH) diabetic peer support program's (DPSP) impact 4 years after its establishment by assessing knowledge, self-efficacy and behaviours of DPSP members compared to non-members. Methodology: This is a cross-sectional study done among diabetic patients attending clinics between 12th August and 25th September 2018 at KCH. Self and interviewer-administered questionnaires (designed based on validated survey instruments) were used. The participants (n=176) were recruited consecutively after consenting. Results: Results showed DPSP members were more knowledgeable regarding the effects of skipping meals and sweet juice on blood glucose and conditions not associated with diabetes. In terms of self-efficacy and behaviour changes, DPSP members believe that they are more able to correct hypoglycaemia, to communicate their concerns to health workers and to perform daily foot exam compared to non-members. Conclusion: The KCH (Lilongwe) Diabetes Peer Support program has positively impacted its members and should be scaled up to engage all diabetic patients in Malawi. Ongoing training for peer supporters is necessary to update and reinforce management, knowledge and skills, and to ensure fidelity in program implementation.

Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression.

The inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case-control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.