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The present study aimed to test if perceived pubertal timing was related to marijuana and alcohol use through deviant peer affiliation. Additionally, we examined if the deviant peer pathway was moderated by impulsiveness, gender, or both. Data were collected from 342 youth, most of whom had a family history of substance use disorder. Youth completed assessments every six months from age 13 to 16. For girls only, longitudinal analyses revealed that perceived pubertal timing was indirectly related to substance use through higher levels of deviant peer affiliation. This pathway was moderated by impulsiveness such that the association between perceived pubertal timing and deviant peer affiliation was only present for girls with average to high levels of impulsiveness. These findings elucidate a developmental pathway from perceived pubertal timing to substance use through deviant peer affiliation for high-risk girls, although low levels of impulsiveness were protective.

Abstract Investment in Strep A vaccine R&D is disproportionately low relative to the large burden of Strep A diseases globally. This study presents a novel Strep A vaccine global demand and financial forecast model with estimates of potential global demand and associated revenue and profits for a hypothetical Strep A vaccine as well as a net present value (NPV) analysis of return on capital investments required to develop the vaccine. A positive NPV was calculated for a variety of developer scenarios and target populations, including the global rollout of the vaccine in private and public markets by a multinational pharmaceutical corporation and a staged rollout by a developing country vaccine manufacturer for both infant and child populations. The results suggest there is a viable commercial market for a Strep A vaccine. It is hoped that this study will help to inform industry decision-making and drive increased prioritization of, and investment in, Strep A vaccine research and development.

This study aimed to evaluate assessment and referral practices for the early detection and diagnosis of children at risk for or with cerebral palsy (CP) by health care and education providers in Maryland and Delaware. A secondary aim was to identify barriers for using early detection tools and identify opportunities for change to support early diagnosis and improve care. Seventy-two participants answered ≥ 50% of the survey questions. Most were occupational or physical therapists (86%) working in early intervention (61%). Eighty-eight percent indicated awareness that CP can be diagnosed by 12 months. Though 86% stated they typically suspect a diagnosis of CP between 0 and 12 months, only 19% reported that their patients received a CP diagnosis < 12 months. The Developmental Assessment of Young Children (73%) and the Peabody Developmental Motor Scales-2 (59%) were used most. Many respondents indicated never using magnetic resonance imaging (70%), the General Movements Assessment (87%), or the Hammersmith Infant Neurological Exam (69%). Participants identified clinical signs and symptoms prompting a referral for the diagnostic assessment of CP, most commonly stiffness in legs (95%), excessive head lag (93%), and persistent fisting (92%). Policy and organizational change, clinician education, and training are needed to support the implementation of CP early detection guidelines.

Abstract Recent efforts have re-invigorated the Streptococcus pyogenes (Group A Streptococcus) vaccine development field, though scientific, regulatory and commercial barriers persist, and the vaccine pipeline remains sparse. There is an ongoing need to accelerate all aspects of development to address the large global burden of disease caused by the pathogen. Building on over 100 years of S. pyogenes vaccine development, there are currently eight candidates on a product development track, including four M protein-based candidates and four candidates designed around non-M protein antigens. These candidates have demonstrated proof of concept for protection against S. pyogenes in preclinical models, one has demonstrated safety and immunogenicity in a Phase 1 trial and at least four others are poised to soon enter clinical trials. To maintain momentum, the Strep A Vaccine Global Consortium (SAVAC) was established to bring together experts to accelerate global S. pyogenes vaccine development. This article highlights the past, present and future of S. pyogenes vaccine development and emphasizes key priorities, and the role of SAVAC, in advancing the field.

Abstract Background Among older adults, postoperative urinary tract infection is associated with significant harms including increased risk of hospital readmission and perioperative mortality. While risk of urinary tract infection is known to increase with age, the independent association between frailty and postoperative urinary tract infection is unknown. In this study we used 2014–2018 data from the U.S. National Surgical Quality Improvement Program (NSQIP) to investigate whether frailty is an independent risk factor for postoperative urinary tract infection, controlling for age and other relevant confounders. Methods Frailty was assessed using the modified Frailty Index. Postoperative urinary tract infection was defined as any symptomatic urinary tract infection (of the kidneys, ureters, bladder, or urethra) developing within 30 days of the operative procedure. To examine associations between frailty and other specific factors and postoperative urinary tract infection, chi squared tests, students t-tests, and logistic regression modelling were used. Results Urinary tract infection was identified after 22,356 of 1,724,042 procedures (1.3%). In a multivariable model controlling for age and other patient and surgical characteristics, the relative odds for urinary tract infection increased significantly with increasing frailty score. For example, compared to a frailty score of 0, the relative odds for urinary tract infection for a frailty score of 3 was 1.50 (95% confidence interval 1.41, 1.60). The relative odds associated with the maximum frailty score (5) was 2.50 (95% confidence interval 1.73, 3.61). Conclusions Frailty is associated with postoperative urinary tract infection, independent of age. Further research should focus on the underlying mechanisms and strategies to mitigate this risk among frail adults.

Abstract Background Research on nutrition-sensitive agriculture (NSA) has mostly been aimed at demonstrating its impact on nutrition and explicating underlying pathways, and more rarely at understanding processes and lessons learnt from them. This study aimed to gain insights into the processes that influence behaviour change, contributing to improved caring, feeding and food production practices, using a program theory perspective. It also investigated perceived challenges to the sustainability of interventions and potential solutions, in the context of an NSA program in rural Vietnam. Using a participatory approach, data were gathered on impact pathways and perceived outcomes, on elements of program theory that led to behavioural change, as well as barriers and facilitators. Respondents in semi-structured interviews (n = 30) and seven focus group discussions (total n = 76) were selected purposively among program participants. Data was collected and triangulated across several stakeholder groups. Results The impact pathways (production-consumption, caring and feeding, and home-grown school feeding) envisaged in the NSA program functioned as intended; synergies were revealed. The increased supply of locally produced nutrient-rich foods not only contributed to the emergence of a promising income sub-pathway but also reinforced synergy with the home-grown school feeding pathway. Improved diets, feeding and caring practices, and school attendance were key outcomes of the program. Successful elements were pathway-specific, such as flexibility in implementing context-appropriate agricultural models. Others, such as benefit-driven motivation and improved knowledge, triggered changes in multiple pathways. Role models, increased self-confidence, and change agents were the main process facilitators. The biggest barrier to both implementation and sustainability was the poor socio-economic conditions of the most disadvantaged households. Conclusions This study showed the relevance of NSA programs in addressing undernutrition in remote areas by enhancing self-reliance in local communities. The integration of behaviour change activities proved to be a key strategy in the process to enhance the impact of agriculture on nutrition outcomes. Though outcomes and influencing factors are very context-dependent, lessons on what worked and what did not work could inform the design and implementation of effective behaviour change strategies in future NSA programs in Vietnam and elsewhere.

Abstract Background The stigmatization of mental health problems is a primary barrier for young people to approach mental health services when they suspect they might have such problems. Nevertheless, the internet has become a common platform on which they are likely to seek information on mental health. As such, this study aimed to explore responses from secondary school students in Can Tho city regarding suckhoetre.vn website. This website provided information on health and mental health, and this study assessed the potential relevance, appeal, accessibility, usefulness, and sustainability of the website. Methods A cross-sectional study included 643 secondary school students in Can Tho city selected by cluster sampling. Two weeks after the students were introduced to the website, they were invited to evaluate it using an anonymous questionnaire. The Chi-squared test was used to assess the significance of differences in the distribution of selected students’ sociodemographic characteristics. Results Most (98.6%) participants visited the website in the two-week period, 74% once or twice a week, the others more often, up to once a day. Their activities included reading information (85.8%), seeking help (17.7%), sharing information (15.5%), giving advice to others (11.0%), and chatting or giving comments (9.8%). Most students rated the website very highly in terms of appeal, relevance, accessibility, and usefulness, and wanted to have access to the website in the future. These findings are positive signals to pursue the possible use of a website on mental health for secondary school students to help raise awareness and support good mental health among adolescents in Can Tho city and beyond. Conclusion A website designed to provide information to secondary school students appeared to be a promising way to provide access to information on the topic of mental health. The website should be maintained and introduced widely to students, teachers and parents, with regular evaluation of the effectiveness of this website.

Abstract In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Abstract Anthracyclines are highly effective chemotherapeutic agents; however, their clinical utility is limited by severe anthracycline-induced cardiotoxicity (ACT). Genome-wide association studies (GWAS) have uncovered several genetic variants associated with ACT, but the impact of these findings requires further elucidation. We conducted a transcriptome-wide association study (TWAS) using our previous GWAS summary statistics (n = 280 patients) to identify gene expression-related associations with ACT. We identified a genetic association between decreased expression of GDF5 and ACT (Z-score = −4.30, P = 1.70 × 10−5), which was replicated in an independent cohort (n = 845 patients, P = 3.54 × 10−3). Additionally, cell viability of GDF5-silenced human cardiac myocytes was significantly decreased in response to anthracycline treatment. Subsequent gene set enrichment and pathway analyses of the TWAS data revealed that genes essential for survival, cardioprotection and response to anthracyclines, as well as genes involved in ribosomal, spliceosomal and cardiomyopathy pathways are important for the development of ACT.

Abstract Background Primary health care (PHC), of which preventive medicine (PM) is a subspecialty, will have to cope with a deficiency of staff in the future, which makes the retention of graduates urgent. This study was conducted in Vietnam, where PM is an undergraduate degree in parallel to medical training. It aims to identify facilitating and hindering factors that impact recruitment and retention of PM graduates in the specialty. Methods A cross-sectional study enrolled 167 graduates who qualified as PM doctors from a Vietnamese medical school, between 2012 and 2018. Data were collected via an online questionnaire that asked participants about their motivation and continuation in PM, the major life roles that they were playing, and their satisfaction with their job. Multiple regression analyses were used to identify which life roles and motivational factors were related to the decision to take a PM position and to stay in the specialty, as well as how these factors held for subgroups of graduates (men, women, graduates who studied PM as their first or second study choice). Results Half of the PM graduates actually worked in PM, and only one fourth of them expressed the intention to stay in the field. Three years after qualification, many graduates had not yet decided whether to pursue a career in PM. Satisfaction with opportunities for continuous education was rated as highly motivating for graduates to choose and to stay in PM. Responsibility for taking care of parents motivated male graduates to choose PM, while good citizenship and serving the community was associated with the retention of graduates for whom PM was their first choice. Conclusions The findings demonstrate the importance of social context and personal factors in developing primary care workforce policy. Providing opportunities for continued education and enhancing the attractiveness of PM as an appropriate specialty to doctors who are more attached to family and the community could be solutions to maintaining the workforce in PM. The implications could be useful for other less popular specialties that also struggle with recruiting and retaining staff.

The Near-Earth Object (NEO) Surveyor mission is a NASA Observatory designed to discover and characterize asteroids and comets. The mission’s primary objective is to find the majority of objects large enough to cause severe regional impact damage (>140 m in effective spherical diameter) within its 5 yr baseline survey. Operating at the Sun–Earth L1 Lagrange point, the mission will survey to within 45° of the Sun in an effort to find objects in the most Earth-like orbits. The survey cadence is optimized to provide observational arcs long enough to distinguish near-Earth objects from more distant small bodies that cannot pose an impact hazard reliably. Over the course of its survey, NEO Surveyor will discover ∼200,000–300,000 new NEOs down to sizes as small as ∼10 m and thousands of comets, significantly improving our understanding of the probability of an Earth impact over the next century.

We present optical and infrared imaging and spectroscopy of the R Coronae Borealis-type (R Cor Bor) star IRAS 00450+7401. Optical spectra further confirm its classification as a cool R Cor Bor system, having a hydrogen-deficient carbon star spectral subclass of HdC5 or later. Mid-infrared spectroscopy reveals the typical ∼8 μ m “hump” seen in other R Cor Bor stars and no other features. A modern-epoch spectral energy distribution shows bright emission from hot dust having T _dust > 600 K. Historical infrared data reveal generally cooler dust color temperatures combined with long-term fading trends, but provide no discernible correlation between flux level and temperature. Investigating the most mid-infrared variable R Cor Bor stars found in IRAS, AKARI, and WISE data reveals similar fading trends, bursts that can show a factor of up to 10 change in flux density between epochs, and blackbody-fit dust color temperatures that span 400–1300 K. While some R Cor Bor stars such as IRAS 00450+7401 appear to undergo fade/burst cycles in the mid-infrared, significant gaps in temporal coverage prevent conclusively identifying any preferred timescale for their mid-infrared variability and circumstellar dust temperature changes.

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

Abstract Background It is increasingly recognized that improving the quality of maternal health care delivery is of utmost importance in many countries. In Laos, the quality of antenatal care (ANC) service remains inadequate, but it has never been assessed thoroughly. This study aims to determine the ANC quality at the urban and rural public health facilities in Laos and provides suggestions to improve health education and counseling in addition to other routine care in public ANC services. Methods This health-facility based, cross-sectional observation study included both health providers (n = 77) and pregnant women (n = 421) from purposively selected health facilities (n = 16). Information on the mothers’ current pregnancies, previous visits and their last children was collected. The time spent for each ANC session as well as ANC services provided were recorded. Descriptive and inferential statistics were applied to analyze the data. Results Overall performance of ANC services by health care providers was poor in both urban and rural areas. Insufficient provision of information on danger signs during pregnancy, nutrition, breast feeding and iron supplements was revealed. Generally the communication skills, behavior and attitude of health providers were very poor. Less than a quarter of pregnant women were treated with kindness and respect. Only 4% of the observed ANC session took privacy into consideration. Less than 10% of available information materials were used during each ANC session. None of the health providers in both rural and urban areas performed specific counseling. Overall mean (SD) time-spent for each ANC session was 16.21 (4.28) minutes. A positive correlation was identified between the length of working experience of health providers and their physical performance scores (adjusted R square = 0.017). Conclusions The overall performance of ANC services by health care providers was inadequate in both urban and rural areas. Insufficient provision of health education and poor communication skills of health care providers were revealed. Existing IEC materials were scarcely used. Taking action to improve the quality of ANC services by training and providing specific guidelines, creating dedicated rooms, and providing sufficient and effective materials for counseling are all greatly needed in public health facilities in Laos.

Abstract Background Recruiting and retaining students in preventive medical (PM) specialties has never been easy; one main challenge is how to select appropriate students with proper motivation. Understanding how students perceive PM practice differently from practicing doctors is necessary to guide students, especially for those for whom PM is only a substitute for medicine as their first study preference, properly during their study and, later, the practice of PM. Methods One thousand three hundred eighty-six PM students in four Vietnamese medical schools and 101 PM doctors filled out a questionnaire about the relevance of 44 characteristics of working in PM. ANOVAs were conducted to define the relationship between students’ interest, year of study, willingness to work in PM, and the degree to which students had realistic perceptions of PM practice, compared to doctors’ perceptions. Results Overall, compared to doctors’ perceptions, students overestimated the importance of most of the investigated PM practice’s characteristics. Moreover, students’ perception related to their preference and willing to pursue a career in PM after graduation. In particular, students for whom PM was their first choice had more realistic perceptions of community practice than those who chose PM as their second choice. And, second-choice students had more realistic perceptions than first-choice students in their final years of study, but expected higher work stress in PM practice. Students who were willing to pursue a career in PM rated the importance of community practice higher than those who were not. We also found that students’ perception changed during training as senior students had more realistic perceptions of clinical aspects and working stress than junior students, even though they overemphasized the importance of the community aspects of PM practice. Conclusions To increase the number of students actually entering the PM field after graduation, the flawed perceptions of students about the real working environment of PM doctors should be addressed through vocation-oriented activities in the curriculum targeted on groups of students who are most likely to have unrealistic perceptions. Our findings also have implications for other less attractive primary health care specialties that experience problems with recruiting and retaining students.

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa.Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations.Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

Nuclear-factor-E2-related factor 2 (Nrf2) is a key transcription factor for the regulation of cellular responses to cellular stress and inflammation, and its expression is significantly lower after spontaneous term labor in human fetal membranes. Pathological induction of inflammation can lead to adverse pregnancy outcomes such as pre-eclampsia, preterm labor, and fetal death. As stretch forces are known to act upon the fetal membranes in utero, we aimed to ascertain the effect of stretch on Nrf2 to increase our understanding of the role of this stimulus on cells of the amnion at term. Our results indicated a significant reduction in Nrf2 expression in stretched isolated human amnion epithelial cells (hAECs) that could be rescued with sulforaphane treatment. Downregulation of Nrf2 as a result of stretch was accompanied with activation of proinflammatory nuclear factor-kB (NF-kB) and increases in LDH activity, ROS, and HMGB1. This work supports stretch as a key modulator of cellular stress and inflammation in the fetal membranes. Our results showed that the modulation of the antioxidant response pathway in the fetal membranes through Nrf2 activation may be a viable approach to improve outcomes in pregnancy.

The idea that cellular stress (including that precipitated by stretch), plays a significant role in the mechanisms initiating parturition, has gained considerable traction over the last decade. One key consequence of this cellular stress is the increased production of Danger Associated Molecular Patterns (DAMPs). This diverse family of molecules are known to initiate inflammation through their interaction with Pattern Recognition Receptors (PRRs) including, Toll-like receptors (TLRs). TLRs are the key innate immune system surveillance receptors that detect Pathogen Associated Molecular Patterns (PAMPs) during bacterial and viral infection. This is also seen during Chorioamnionitis. The activation of TLR commonly results in the activation of the pro-inflammatory transcription factor Nuclear Factor Kappa-B (NF-kB) and the downstream production of pro-inflammatory cytokines. It is thought that in the human fetal membranes both DAMPs and PAMPs are able, perhaps via their interaction with PRRs and the induction of their downstream inflammatory cascades, to lead to both tissue remodeling and weakening. Due to the high incidence of infection-driven Pre-Term Birth (PTB), including those that have preterm Premature Rupture of the Membranes (pPROM), the role of TLR in fetal membranes with Chorioamnionitis has been the subject of considerable study. Most of the work in this field has focused on the effect of PAMPs on whole pieces of fetal membrane and the resultant inflammatory cascade. This is important to understand, in order to develop novel prevention, detection, and therapeutic approaches, which aim to reduce the high number of mothers suffering from infection driven PTB, including those with pPROM. Studying the role of sterile inflammation driven by these endogenous ligands (DAMPs) activating PRRs system in the mesenchymal and epithelial cells in the amnion is important. These cells are key for the maintenance of the integrity and strength of the human fetal membranes. This review aims to (1) summarize the knowledge to date pertinent to the role of DAMPs and PRRs in fetal membrane weakening and (2) discuss the clinical potential brought by a better understanding of these pathways by pathway manipulation strategies.

Background: There is a correlation between self-esteem in adolescents and risks and protective factors for their health and welfare. The study was conducted to determine the prevalence of low self-esteem and sociodemographic features related to anxiety, depression, educational stress, and suicidal ideation in secondary school students in Vietnam.Methods: A cross-sectional design was employed for this study with participation of 1,149 students in Cantho City in Vietnam. A structured questionnaire was applied to ask about self-esteem, depression, anxiety, educational stress, and suicidal ideation.Results: Students with low self-esteem were detected at a prevalence of 19.4%. High educational stress and physical and emotional abuse by parents or other adults in the household were major risk factors correlated to low self-esteem, while a protective factor for low self-esteem was attending supplementary classes. An association among lower self-esteem and increased anxiety, depression, and suicidal ideation was detected.Conclusions: Self-esteem is associated with anxiety, depression, and academic stress, which significantly affect students’ quality of life and links to suicidal ideation. These results therefore suggested the need for a school-based or web-based provision aimed at proactively increasing students’ self-esteem and skills for dealing with academic stress.

An interdisciplinary team of university faculty members collaborated to develop an intervention to address a deficiency in student information literacy skills. The team developed video modules that instruct users how to create, use and maintain a ProQuest RefWorks account; a citation management software (CMS) tool that is compatible with Google Docs word processing. The research team collected YouTube and ProQuest RefWorks analytics as well as pre/post survey data from university students who participated in a pilot using the video modules. Results indicate that the modules impacted student information literacy skills; specifically, in-text citation and referencing. Based on the results, we also describe next steps for this research.

Background: The detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29 years by the National Institutes for Health (NIH) criteria which include ≥6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling and learning difficulties has introduced substantial heterogeneity to the NIH criteria. Methods: We have defined the sensitivity of comprehensive RNA analysis on blood of presumed NF1 patients meeting NIH criteria with at least one nonpigmentary criterion and determined the proportion of children with ≥6 CAL and no family history that has an NF1 or SPRED1 genetic variant. RNA analysis was carried out from 04/2009–12/2015 on 361 NF1 patients. Findings: A presumed causative NF1 mutation was found in 166/171 (97.08%–95% CI 94.56–99.6%) of familial cases and 182/190 (95.8%–95% CI 92.93–98.65%) sporadic de novo cases. Two of thirteen (15%) mutation negative individuals had dysembryoplastic neuroepithelial tumour (DNET) compared to 2/348 (0.6%) with an NF1 variant (p = 0.007). No SPRED1 variants were found in the thirteen individuals with no NF1 variant. Of seventy-one individuals with ≥6 CAL and no non-pigmentary criterion aged 0–20 years, 47 (66.2%) had an NF1 variant six (8.5%) a SPRED1 variant and 18 (25.3%) no disease causing variant. Using the 95.8% detection rate the likelihood of a child with ≥6 CAL having constitutional NF1 drops from 2/3 to 1/9 after negative RNA analysis. Interpretation: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.

Paratesticular tumors are rare and often benign causes of scrotal masses. Intrascrotal angiolipomas are an uncommon paratesticular tumor that has seldom been reported in the literature. This report describes a 77 year old man who presented with a 15 cm extratesticular mass. The mass was removed due to increasing discomfort and specimen pathology confirmed it as an angiolipoma. This case highlights the feasibility of conservative management for slow growing masses, such as angiolipomas.

Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the “golden age” of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections.

OBJECTIVES:The purposes of this study were to assess the adherence to medication of hypertensive patients visiting community health stations in a rural area in Vietnam, to examine the relationship between levels of adherence and cardiovascular risk among hypertensive patients and to further understand factors influencing adherence. METHODS:This study is part of a prospective one-year study conducted on hypertension management in a population aged 35 to 64 years. Data on age, sex, blood pressure and blood test results were collected at baseline. Cardiovascular risk was based on the Cardiovascular Risk Prediction Model for populations in Asia. To calculate medication adherence, the number of days the drug was taken was divided by the number of days since the first day of the prescription. A threshold of 80% was applied to differentiate between adherence and non-adherence. In-depth interviews were conducted among 18 subjects, including subjects classified as adherent and as non-adherent. RESULTS:Among 315 patients analyzed, 49.8% of the patients were adherent. Qualitative investigation revealed discrepancies in classification of adherence and non-adherence based on quantitative analysis and interviews. No significant difference in medication compliance between two cardiovascular disease risk groups (10% risk) was found, also not after controlling for age, sex, and ethnicity (adjusted odds ratio at 1.068; 95% CI: 0.614 to 1.857). The odds of medication adherence in females was 1.531 times higher than in males but the difference was not statistically significant (95% CI: 0.957 to 2.448). Each one-year increase in age resulted in patients being 1.036 times more likely to be compliant (95% CI: 1.002 to 1.072). Awareness of complications related to hypertension was given as the main reason for adherence to therapy. CONCLUSIONS:Medication adherence rate was relatively low among hypertensive subjects. The data suggest that rather than risk profile, the factor of age should be considered for guiding the choice on who to target for improving medication adherence.

OBJECTIVE:To inform development of guidelines for hypertension management in Vietnam, we evaluated the cost-effectiveness of different strategies on screening for hypertension in preventing cardiovascular disease (CVD). METHODS:A decision tree was combined with a Markov model to measure incremental cost-effectiveness of different approaches to hypertension screening. Values used as input parameters for the model were taken from different sources. Various screening intervals (one-off, annually, biannually) and starting ages to screen (35, 45 or 55 years) and coverage of treatment were analysed. We ran both a ten-year and a lifetime horizon. Input parameters for the models were extracted from local and regional data. Probabilistic sensitivity analysis was used to evaluate parameter uncertainty. A threshold of three times GDP per capita was applied. RESULTS:Cost per quality adjusted life year (QALY) gained varied in different screening scenarios. In a ten-year horizon, the cost-effectiveness of screening for hypertension ranged from cost saving to Int$ 758,695 per QALY gained. For screening of men starting at 55 years, all screening scenarios gave a high probability of being cost-effective. For screening of females starting at 55 years, the probability of favourable cost-effectiveness was 90% with one-off screening. In a lifetime horizon, cost per QALY gained was lower than the threshold of Int$ 15,883 in all screening scenarios among males. Similar results were found in females when starting screening at 55 years. Starting screening in females at 45 years had a high probability of being cost-effective if screening biannually was combined with increasing coverage of treatment by 20% or even if sole biannual screening was considered. CONCLUSION:From a health economic perspective, integrating screening for hypertension into routine medical examination and related coverage by health insurance could be recommended. Screening for hypertension has a high probability of being cost-effective in preventing CVD. An adequate screening strategy can best be selected based on age, sex and screening interval.

The study aims to inform potential cost-effectiveness analysis of hypertension management in Vietnam by providing utilities and predictors of utilities in patients with hypertension.Hypertensive patients up to 80 years old visiting the hospital were invited to participate in a survey using Quality Metric's Short-form 36v2TM translated into Vietnamese. Health-state utilities were estimated by applying a previously published algorithm.The mean utility of the 691 patients interviewed was 0.73. Controlling for age, sex, blood pressure (BP) stage, and history of stroke, the utilities in older patients were lower than those in younger ones, and statistically significantly different between the extremes of youngest and oldest groups (p = 0.03). Utility in males was higher than in females (p = 0.002). As expected, patients with a history of stroke appeared to exhibit lower utilities than patients without such history, but the difference was not statistically significant (p = 0.73). Patients with more than three comorbidities did have lower utilities than patients without comorbidity (p = 0.01).Health-state utilities found among hypertensive patients in Vietnam were similar to those found in other international studies. It is suggested that lower of health-state utilities exist among those patients who were older, female or had more than three comorbidities in comparison with respective reference groups. However, further research for confirmation is required. The data from this study provide a potential reference on health-state utilities of hypertensive patients in Vietnam as an input for future cost-effectiveness analysis of interventions. Also, it may serve as a reference for other similar populations, especially in the context of similar environments in low income countries.

An increased risk of neoplasm has been noted when bowel segments are used for urinary diversion. Particularly true for ureterosigmoidostomy, colonic adenocarcinoma has rarely been reported following Indiana Pouch diversion. This report describes a 42-year-old woman with a history of bladder exstrophy who developed a polyp in her Indiana Pouch 24 years after its creation. The polyp, found incidentally, was a tubular adenoma with high-grade dysplasia. Due to its malignant potential, the polyp was resected with preservation of the Indiana Pouch. This case highlights the need for lifetime surveillance in urinary reservoir patients who received diversions at a young age.

We conducted a neurophysiological study of attempted speech production in a paralyzed human volunteer using chronic microelectrode recordings. The volunteer suffers from locked-in syndrome leaving him in a state of near-total paralysis, though he maintains good cognition and sensation. In this study, we investigated the feasibility of supervised classification techniques for prediction of intended phoneme production in the absence of any overt movements including speech. Such classification or decoding ability has the potential to greatly improve the quality-of-life of many people who are otherwise unable to speak by providing a direct communicative link to the general community. We examined the performance of three classifiers on a multi-class discrimination problem in which the items were 38 American English phonemes including monophthong and diphthong vowels and consonants. The three classifiers differed in performance, but averaged between 16-21% overall accuracy (chance-level is 1/38 or 2.6%). Further, the distribution of phonemes classified statistically above chance was non-uniform though 20 of 38 phonemes were classified with statistical significance for all three classifiers. These preliminary results suggest supervised classification techniques are capable of performing large scale multi-class discrimination for attempted speech production and may provide the basis for future communication prostheses.

Brain-machine interfaces (BMIs) involving electrodes implanted into the human cerebral cortex have recently been developed in an attempt to restore function to profoundly paralyzed individuals. Current BMIs for restoring communication can provide important capabilities via a typing process, but unfortunately they are only capable of slow communication rates. In the current study we use a novel approach to speech restoration in which we decode continuous auditory parameters for a real-time speech synthesizer from neuronal activity in motor cortex during attempted speech.Neural signals recorded by a Neurotrophic Electrode implanted in a speech-related region of the left precentral gyrus of a human volunteer suffering from locked-in syndrome, characterized by near-total paralysis with spared cognition, were transmitted wirelessly across the scalp and used to drive a speech synthesizer. A Kalman filter-based decoder translated the neural signals generated during attempted speech into continuous parameters for controlling a synthesizer that provided immediate (within 50 ms) auditory feedback of the decoded sound. Accuracy of the volunteer's vowel productions with the synthesizer improved quickly with practice, with a 25% improvement in average hit rate (from 45% to 70%) and 46% decrease in average endpoint error from the first to the last block of a three-vowel task.Our results support the feasibility of neural prostheses that may have the potential to provide near-conversational synthetic speech output for individuals with severely impaired speech motor control. They also provide an initial glimpse into the functional properties of neurons in speech motor cortical areas.

The aim of this study was to define the role of the alpha-adrenergic receptor in the regulation of lipolysis by human adipocytes. Glycerol production by isolated human adipocytes was stimulated by the pure beta-adrenergic agonist isoproterenol in a dose-dependent fashion. This stimulation of lipolysis was inhibited by the alpha-adrenergic agonists methoxamine, phenylephrine, and clonidine. Epinephrine-stimulated lipolysis was potentiated by the alpha-adrenergic antagonists, dihydroergocryptine, phentolamine, phenoxybenzamine, and yohimbine. Whereas the attenuation of beta-adrenergic agonist-stimulated lipolysis by alpha-adrenergic agonists was reversed completely by the alpha 2-adrenergic antagonist yohimbine, the alpha 1-antagonist prazosin did not reverse such attenuation. It is concluded that alpha-adrenergic agonists act as antilipolytic agents in human adipocytes and that this action may result from the interaction of these compounds with a population of alpha 2-adrenergic receptors.