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.

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.

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.

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.

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.

Educating junior doctors and pharmacists to reduce discharge prescribing of opioids for surgical patients: a cluster randomised controlled trial.

OBJECTIVES: To evaluate whether educating junior doctors and hospital pharmacists about analgesic prescribing improved discharge prescribing of opioids for opioid-naïve patients after surgical admissions. DESIGN: Cluster randomised controlled trial, undertaken during the first half of 2019. SETTING: The Alfred Hospital, a major Melbourne teaching hospital with 13 surgical units. PARTICIPANTS: Opioid-naïve patients discharged from surgical units after a stay of at least 24 hours. INTERVENTION: Surgical units were randomised to the intervention or control arms. Interns, residents, and clinical pharmacists assigned to intervention arm units attended education sessions, presented by the hospital analgesic stewardship pharmacist, about appropriate analgesic prescribing for patients in hospital surgical units. MAIN OUTCOME MEASURES: The patients prescribed slow release opioids on discharge from hospital during the baseline (1 February - 30 April 2018) and post-intervention periods (17 February - 30 April 2019). RESULTS: During the baseline period, 1369 intervention unit and 1014 control unit admissions were included in our analysis; during the evaluation period, 973 intervention unit and 706 control unit episodes were included. After adjusting for age, length of stay, pain score, acute pain service involvement, and use of immediate release opioids prior to admission, patients in the intervention group were prescribed slow release opioids at discharge less frequently than patients in the control group (adjusted odds ratio [aOR], 0.52; 95% CI, 0.35-0.77) and were more frequently discharged without any prescribed opioids following the intervention (aOR, 1.69; 95% CI, 1.24-2.30). Providing de-escalation plans was more frequent for intervention than control group patients prescribed slow release opioids on discharge post-intervention (OR, 2.36; 95% CI, 1.25-4.45). CONCLUSIONS: Specific education for clinicians and pharmacists about appropriate analgesic prescribing for surgical patients is effective in reducing prescribing of opioids at discharge. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000876291 (prospective).

Contraceptive Counseling in the Postpartum Period: Could Pediatricians Have a Role?

INTRODUCTION: Unplanned pregnancies lead to adverse health outcomes and contribute to economic burdens. A lack of continuity and consistency in immediate postpartum care may be a contributor. The most frequent postpartum medical encounters occur with the child's pediatric health care provider, which represents an opportunity to discuss postpartum contraception. Therefore, our objective was to evaluate postpartum family planning knowledge and behavior in women, and to assess the potential acceptability of a pediatrician-delivered intervention to improve knowledge of and convenient access to contraception among postpartum women. METHODS: This was a non-interventional pilot study that employed survey and interview methodology. RESULTS: Women attending pediatric visits for their newborn or infant (N = 346) were surveyed; 35 were interviewed. On average, respondents were 27 years old (SD = 6), 6 months postpartum (SD = 5), and resumed sex 8 weeks after delivery (SD = 6). Of those who had resumed sex, 68% were not using contraception at the time. However, only 18% of survey respondents wanted to have another child. Few exhibited accurate knowledge of birth spacing or long acting reversible contraception. Most interviewees (86%) supported the idea of pediatricians providing contraceptive counseling. Concerns identified included whether it was "allowable" and pediatrician's lack of knowledge of complex maternal health histories. DISCUSSION: This study highlights a gap between contraceptive need and provision in postpartum women. However, the findings suggest women's willingness to engage in conversations with their child's pediatrician about family planning. Future research should assess the feasibility and impact of integrating postpartum counseling into pediatric visits.

Free Clinic Patients' Perceptions and Barriers to Applying for Health Insurance After Implementation of the Affordable Care Act.

Despite implementation of the Affordable Care Act (ACA), many Americans remain uninsured and receive care in free clinics. It is unknown what free clinic attendees in Pennsylvania know about health insurance expansion or what they perceive as barriers in enrolling in health insurance. The objective of this study was to assess the perceptions and experiences of free clinic patients from southwestern Pennsylvania when applying for health insurance after implementation of the ACA. We designed and implemented a survey of patients at three free clinics within Allegheny County, Pennsylvania from September 2016 to February 2017. Our survey included 22-items, 7 sociodemographic questions and 15 questions regarding the patient's health status and their perspectives related to obtaining health insurance. Data was obtained from 203 patient surveys; 110 (55.3%) of the respondents were men and 99 (48.8%) were African American. There were 48 respondents (24.1%) who did not report any income at the time of the study, and of those that did report an income, 92 (46.2%) respondents reported an income below 133% of the federal poverty level. The main barriers patients faced when applying for health insurance were: (1) lack of knowledge about health insurance (n = 127, 58.1%), (2) cost of health coverage (n = 85, 41.9%), (3) lack of resources (n = 83, 40.4%), and (4) lack of enrollment documentation (n = 43, 23.8%). Significant work is needed to better educate patients about their eligibility and options for health insurance. Free clinics can play a key role in eliminating barriers to health insurance enrollment.

A single amino acid substitution in the NS4B protein of Dengue virus confers enhanced virus growth and fitness in human cells in vitro through IFN-dependent host response.

Dengue virus (DENV) replication between mosquito and human hosts is hypothesized to be associated with viral determinants that interact in a differential manner between hosts. However, the understanding of inter-host viral determinants that drive DENV replication and growth between hosts is limited. Through the use of clinical isolates, we identified an amino acid variation of Ala, Met and Val at position 116 of DENV-1 NS4B. While the proportion of virus with the NS4B-116V variant remained constantly high in serial passages in a mosquito cell line, populations of the NS4B-116M and NS4B-116A variants became dominant after serial passages in mammalian cell lines. Using recombinant DENV-1 viruses, the Val to Ala or Met alteration at position NS4B-116 (rDENV-1-NS4B-116A and rDENV-1-NS4B-116M) resulted in enhanced virus growth in human cells in comparison to the clone with Val at NS4B-116 (rDENV-1-NS4B-116V). However, the reverse phenomenon was observed in a mosquito cell line. Additionally, in a human cell line, differential levels of IFN-α/ß and IFN-stimulated gene expressions (IFIT3, IFI44L, OAS1) suggested that the enhanced viral growth was dependent on the ability of the NS4B protein to hamper host IFN response during the early phase of infection. Overall, we identified a novel and critical viral determinant at the pTMD3 of NS4B region that displayed differential effects on DENV replication and fitness in human and mosquito cell lines. Taken together, the results suggest the importance of the NS4B protein in virus replication and adaptation between hosts.

Cultural implications of mentoring in sub-Saharan Africa: a qualitative study.

CONTEXT: Although many studies have demonstrated the benefits of mentoring in academic medicine, conceptual understanding has been limited to studies performed in North America and Europe. An ecological model of mentoring in academic medicine can provide structure for a broader understanding of the role of culture in mentoring. OBJECTIVE: The goal of this study was to explore the role of culture in the development and maintenance of mentoring relationships within the context of the University of Malawi College of Medicine. METHODS: A qualitative study using in-depth, semi-structured interviews and thematic analysis was conducted to explore the meaning of mentorship at the study institution. Criterion sampling was used to identify and recruit medical students, interns, registrars and faculty members. Study team members developed a codebook through open coding and applied it to all interview transcripts. Thematic analysis was used to identify and categorise themes according to an ecological model. RESULTS: A total of 46 participants from two major centres in Malawi were interviewed. Themes were identified within three domains: the intrapersonal; the interpersonal, and the institutional. Intrapersonal themes included Malawian politeness, mentoring needs, and friendliness and willingness to help. Interpersonal themes included understanding the role of the mentor, respect for elders, personal and professional boundaries, and perceptions of others. Institutional themes included the supervisor versus mentor, time pressures, tension about the scope of training, and the mentoring cycle. CONCLUSIONS: This study highlights the strengths of and challenges imposed by culture to the provision of mentoring relationships at the study institution. It also highlights the central role of culture in mentoring and proposes an updated model for mentoring in academic medicine. This model can inform future research on mentoring and may serve as a model in the larger effort to provide faculty development in mentoring across sub-Saharan Africa.

Recommendations and Low-Technology Safety Solutions Following Neuromuscular Blocking Agent Incidents.

BACKGROUND: Neuromuscular blocking agents (NMBs) are high-risk medications used to facilitate endotracheal intubation and artificial ventilation. In an incident at a metropolitan tertiary referral and teaching public hospital in Australia, a neurosurgical patient became unresponsive at the start of surgery. It was determined that cisatracurium was administered in error in place of midazolam; the patient was ventilated and the emergency surgery continued. Two additional non-operating room (OR) drug-swap cases involving cisatracurium were reported within 12 months of this event, resulting in a comprehensive review of NMB safety. METHODS: A root cause analysis (RCA) resulted in multiple interventions to decrease the risk of selection and administration errors: (1) review of NMB packaging and introduction of in-house NMB labeling by pharmacy procurement staff before distribution; (2) implementation of a medication administration in anesthetics guideline with ongoing education; (3) audit of storage with removal of NMBs; (4) review of new products by medication safety pharmacists and a senior anesthetist before distribution; and (5) use of red-barrel syringes for administering NMBs was expanded to all areas using NMBs to minimize syringe-swap incidents. RESULTS: In the four years since full implementation of interventions, there have been no reports of cisatracurum selection errors. An incident of atracurium administration resulted in further recommendations for review of OR cart storage. Ongoing monitoring via medication safety walkrounds, by OR staff, by the perioperative pharmacist, and through the hospital's medication incident monitoring system has not detected any further NMB incidents. CONCLUSIONS: Technological solutions have been shown to decrease the risk of NMB errors, yet multifaceted low-technology solutions may be an effective, cheaper alternative.

Utilizing associational resistance for biocontrol: impacted by temperature, supported by indirect defence.

BACKGROUND: Associational herbivore resistance is potentiated by neighbouring heterogenic plant species that impact a focal plant's attraction to herbivores or the damage that they cause. One mechanism to confer associational resistance is believed to be exposure to neighbour-emitted volatiles, the receivers of which range from intra- and interspecific neighbour plants to higher-trophic-level insects. In previous studies the passive adsorption of neighbour-emitted semivolatiles has been reported, but little is known regarding the mechanisms and ecological consequences on the receiver plant and its associated biota. To utilize volatile-based associational resistance for agricultural applications, it is imperative to know its effectiveness under varying diurnal temperatures and whether herbivore natural enemies, providing biological control, are impacted. Mimicking varying diurnal temperatures in a laboratory set-up, we assessed how the tritrophic model system Brassica oleracea var. italica (broccoli)-Plutella xylostella (crucifer specialist herbivore)-Cotesia vestalis (endoparasitoid of P. xylostella) is influenced by exposure to the natural semivolatile emitter plant Rhododendron tomentosum Harmaja. RESULTS: Rhododendron tomentosum-exposed B. oleracea was less susceptible to P. xylostella oviposition at both night-time (12°C) and day-time (22°C) temperatures and less favoured and damaged by P. xylostella larvae at 12°C. Exposure did not interfere with indirect defence, i.e. attraction of the natural enemy C. vestalis on host-damaged, R. tomentosum-exposed B. oleracea under 22°C, while there was a reduction in attraction (marginal preference towards host-damaged B. oleracea) under 12°C. CONCLUSIONS: The ability of R. tomentosum exposure to render associational resistance against an agriculturally important Brassica herbivore P. xylostella without severely compromising the specialist parasitoid C. vestalis host location encourages further studies on the potential of using this naturally abundant plant for biocontrol. The generality of our finding on temperature as a potential regulating mechanism for the efficacy of semivolatile emitter-based associational resistance towards specialist pest larval damage should be further studied in natural and agricultural associations. Our study emphasizes the need to develop techniques to compare volatiles at the leaf versus air interface and associate their appearance and ecological role with times of activity and level of specialisation of herbivores and their natural enemies.

Rifampicin mono-resistant tuberculosis in France: a 2005-2010 retrospective cohort analysis.

BACKGROUND: Rifampicin resistance is a risk factor for poor outcome in tuberculosis. Therefore, we sought to describe the characteristics and management of Rifampicin monoresistant (RMR) tuberculosis (TB) in France. METHODS: We conducted a retrospective cohort analysis in 2012 on RMR TB patients diagnosed in France between 2005 and 2010 by using a national laboratory network. A standardized questionnaire was used to collect basic demographic data, region of birth, history of TB, HIV-coinfection, alcohol use, and antituberculosis treatment. Outcome was assessed after at least 18 months of follow-up. RESULTS: A total of 39 patients with RMR TB were reported (0.12% of all TB cases). Overall, 19 (49%) had a previous history of treatment, 9 (23%) were HIV-coinfected, and 24 (62%) were smear-positive. Patient with secondary RMR were more likely to have alcohol abuse (P = 0.04) and HIV-coinfection (p = 0.04). Treatment outcome could be assessed for 30 patients, the nine others being dead or lost to follow-up. A total of 20 (67%) of the 30 assessed were cured, 3 (10%) died, 3 (10%) relapsed, and 4 (13%) were lost to follow up. Four (13%) received less than 6 months of treatment, 3 did not have any modification of the standardized regimen, 13 (43%) received fluoroquinolones, 4 (13%) aminoglycosides, and 8 (26%) a combination of both. CONCLUSIONS: RMR TB is a rare disease in France, and its management was heterogeneous. The lack of treatment standardization may be a consequence of low expertise and may lead to the unsatisfactory low success rate.

Understanding receptor-mediated effects in rainbow trout: in vitro-in vivo extrapolation using physiologically based toxicokinetic models.

The European REACH regulation requires the use of animal experimentation to assess the risk of industrial chemicals. However, the 3R principle (reduction, replacement, refinement) demands the use of suitable alternative test methods. Many dossiers submitted for the authorization of chemicals have attempted to provide the required data without performing new experiments, relying heavily on in silico methods; in vitro assays were scarcely used. We propose a methodology that uses physiologically based toxicokinetic (PBTK) models to extrapolate in vitro data to the in vivo level. We collected experimental results for in vitro and in vivo ethoxyresorufin-O-deethylase and vitellogenin induction following chemical exposure and compared those results with model predictions. We found that the predictive power of aqueous chemical concentrations was limited; median effect concentrations (EC50s) based on internal concentrations in fish correlated better with in vitro EC50s. Our data show that in vitro assays could offer a substitute for fish studies when combined with PBTK models.

Specialization training in Malawi: a qualitative study on the perspectives of medical students graduating from the University of Malawi College of Medicine.

BACKGROUND: There is a critical shortage of healthcare workers in sub-Saharan Africa, and Malawi has one of the lowest physician densities in the region. One of the reasons for this shortage is inadequate retention of medical school graduates, partly due to the desire for specialization training. The University of Malawi College of Medicine has developed specialty training programs, but medical school graduates continue to report a desire to leave the country for specialization training. To understand this desire, we studied medical students' perspectives on specialization training in Malawi. METHODS: We conducted semi-structured interviews of medical students in the final year of their degree program. We developed an interview guide through an iterative process, and recorded and transcribed all interviews for analysis. Two independent coders coded the manuscripts and assessed inter-coder reliability, and the authors used an "editing approach" to qualitative analysis to identify and categorize themes relating to the research aim. The University of Pittsburgh Institutional Review Board and the University of Malawi College of Medicine Research and Ethics Committee approved this study and authors obtained written informed consent from all participants. RESULTS: We interviewed 21 medical students. All students reported a desire for specialization training, with 12 (57%) students interested in specialties not currently offered in Malawi. Students discussed reasons for pursuing specialization training, impressions of specialization training in Malawi, reasons for staying or leaving Malawi to pursue specialization training and recommendations to improve training. CONCLUSIONS: Graduating medical students in Malawi have mixed views of specialization training in their own country and still desire to leave Malawi to pursue further training. Training institutions in sub-Saharan Africa need to understand the needs of the country's healthcare workforce and the needs of their graduating medical students to be able to match opportunities and retain graduating students.

Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment.

The Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a ground-breaking immunotherapeutic approach in cancer treatment. To overcome the complexity and high manufacturing cost associated with current ex vivo CAR T cell therapy products, alternative strategies to produce CAR T cells directly in the body have been developed in recent years. These strategies involve the direct infusion of CAR genes via engineered nanocarriers or viral vectors to generate CAR T cells in situ. This review offers a comprehensive overview of recent advancements in the development of T cell-targeted CAR generation in situ. Additionally, it identifies the challenges associated with in vivo CAR T method and potential strategies to overcome these issues.