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ABSTRACTSmoking is a potent cause of asthma exacerbations, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most studies of smoking and DNAm have been done using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is lacking. Here, we identified DNAm patterns in the lungs that are altered by smoking. We used an established mouse model to measure the effects of chronic smoke exposure first on lung phenotype immediately after smoking and then after a period of smoking cessation. Next, we determined whether our mouse model recapitulates previous DNAm patterns observed in smoking humans, specifically measuring DNAm at a candidate gene responsive to cigarette smoke, Cyp1a1. Finally, we carried out epigenome-wide DNAm analyses using the newly released Illumina mouse methylation microarrays. Our results recapitulate some of the phenotypes and DNAm patterns observed in human studies but reveal 32 differentially methylated genes specific to the lungs which have not been previously associated with smoking. The affected genes are associated with nicotine dependency, tumorigenesis and metastasis, immune cell dysfunction, lung function decline, and COPD. This research emphasizes the need to study CS-mediated DNAm signatures in directly affected tissues like the lungs, to fully understand mechanisms underlying CS-mediated health outcomes.

Introduction: The shift to processed foods in American diets has increased vitamin and mineral deficiencies among adolescents, impacting growth and health, often manifesting as oral lesions. This review study aimed to explore the link between nutritional deficiencies and adolescent oral health to improve guidance and prevent long-term issues. Methods: A systematic review of literature from 2013 to 2023 was conducted on adolescents aged 10–19 years, using PRISMA guidelines. Searches in PubMed, Web of Science, Dentistry & Oral Sciences Source—Ebscohost, and Scopus included peer-reviewed articles, excluding reviews and non-empirical studies. Data were screened and extracted with independent reviews for accuracy. Results: Malnutrition strongly correlates with poor oral health. Undernourished children have a 60% increase in dental caries, exacerbated by high sugar intake. Early malnutrition delays dental eruption, temporarily protecting against caries, while stunting and infections cause enamel defects. Chronic conditions like cerebral palsy and celiac disease worsen oral health, with risks persisting into adulthood. Conclusions: Nutritional deficiencies and oral health are interconnected, requiring integrated healthcare. Early interventions and holistic strategies can improve outcomes and reduce long-term burdens. Comprehensive health education and routine dental evaluations are essential for prevention and treatment, enhancing health across all demographics.

BackgroundCanadian health systems fare poorly in providing timely access to elective surgical care, which is crucial for quality, trust, and satisfaction.MethodsWe conducted a cross-sectional analysis of surgical wait times for adults receiving non-urgent cataract surgery, knee arthroplasty, hip arthroplasty, gallbladder surgery, and non-cancer uterine surgery in Ontario, Canada, between 2013 and 2019. We obtained data from the Wait Times Information System (WTIS) database. Inter- and intra-hospital and surgeon variations in wait time were described graphically with caterpillar plots. We used non-nested 3-level hierarchical random effects models to estimate variation partition coefficients, quantifying the proportion of wait time variance attributable to surgeons and hospitals.ResultsA total of 942,605 procedures at 107 healthcare facilities, conducted by 1,834 surgeons, were included in the analysis. We observed significant intra- and inter-provider variations in wait times across all five surgical procedures. Inter-facility median wait time varied between six-fold for gallbladder surgery and 15-fold for knee arthroplasty. Inter-surgeon variation was more pronounced, ranging from a 17-fold median wait time difference for cataract surgery to a 216-fold difference for non-cancer uterine surgery. The proportion of variation in wait times attributable to facilities ranged from 6.2% for gallbladder surgery to 23.0% for cataract surgery. In comparison, surgeon-related variation ranged from 16.0% for non-cancer uterine surgery to 28.0% for cataract surgery.ImplicationsThere is extreme variability in surgical wait times for five common, high-volume, non-urgent surgical procedures. Strategies to address surgical wait times must address the variation between service providers through better coordination of supply and demand. Approaches such as single-entry models could improve surgical system performance.

Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).

(1) Background: This study examines vitamin D’s impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as body mass index (BMI) and socioeconomic status (SES) using Chi-square, Mann–Whitney U, Kruskal–Wallis tests, as well as logistic and Poisson regression. (3) Results: This study found a mean DMFT score of 7.36 and a 33.2% prevalence of untreated dental caries. A higher caries prevalence was correlated with a lower SES (p < 0.001), the male gender (p < 0.001), and a higher BMI (p < 0.001). Severe vitamin D deficiency (

Background: In the first year of life, DNA methylation (DNAm) patterns are established and are particularly susceptible to exposure-induced changes. Some of these changes may leave lasting effects by persistently altering gene expression or cell type composition or function, contributing to disease. Objectives: In this discovery study, we investigated DNAm associations with sensitization to peanut, egg, or cow’s milk and hypothesized that genes demonstrating DNAm differences in immune cells may play a role in the development of food sensitization. Methods: Infant sensitization (a skin prick test wheal size that is at least 2 mm greater than the negative control) was measured to peanut, egg, and cow’s milk at age 1 year, and ages of food introduction were reported prospectively. PBMC DNAm was measured in blood samples at 1 year in 144 infants, oversampled for atopy or wheeze. Statistical analysis of Illumina 450k array DNAm data was conducted in R with adjustment for clinical and genetic covariables and a minimum effect size of 1%, false discovery rate of 5%, and medium-confidence false discovery rate threshold of 20%. Results: There were no DNAm differences between infants with and without peanut, egg, or cow’s milk sensitization. Borderline significant sites with high effect sizes were enriched for methylation quantitative trait loci, hinting at genetic factors influencing DNAm at these sites. DNAm patterns did not differ by peanut or egg introduction before or after 12 months. Conclusion: This small pilot study did not show differences in methylation by food sensitization or introduction, but it did demonstrate DNAm patterns linked to genetic variants.

Developing an effective interval-valued time series (ITS) forecasting scheme for electric power generation is an important issue for energy operators and governments when making energy strategic decisions. The existing studies for ITS forecasting only consider basic descriptive information such as center, radius, upper and lower bounds, and overlooks the distribution information within the data interval. In this study, an interval-valued time series forecasting scheme based on probability distribution information features of interval-valued data with machine learning algorithms is proposed to enhance electric power generation forecasting. In the proposed scheme, the central tendency features and dispersion features from the interval-valued data are designed as integrated features sets (IFS) and used as predictor variables. Three methods including supper vector regression and extreme learning machine and multivariate adaptive regression splines based on the IFS are utilized to develop ITS forecasting models. The daily time series of the metered generation from the Australian Energy Market Operator is used to illustrate the proposed scheme. Empirical results show that the proposed ITS forecasting schemes with IFS outperform the eight benchmark models and thus validate that the proposed scheme is an effective alternative for interval-valued electric power generation forecasting.

Abstract Anaerobic fungi and methanogenic archaea are two classes of microorganisms found in the rumen microbiome that metabolically interact during lignocellulose breakdown. Here, stable synthetic co-cultures of the anaerobic fungus Caecomyces churrovis and the methanogen Methanobacterium bryantii (not native to the rumen) were formed, demonstrating that microbes from different environments can be paired based on metabolic ties. Transcriptional and metabolic changes induced by methanogen co-culture were evaluated in C. churrovis across a variety of substrates to identify mechanisms that impact biomass breakdown and sugar uptake. A high-quality genome of C. churrovis was obtained and annotated, which is the first sequenced genome of a non-rhizoid-forming anaerobic fungus. C. churrovis possess an abundance of CAZymes and carbohydrate binding modules and, in agreement with previous studies of early-diverging fungal lineages, N6-methyldeoxyadenine (6mA) was associated with transcriptionally active genes. Co-culture with the methanogen increased overall transcription of CAZymes, carbohydrate binding modules, and dockerin domains in co-cultures grown on both lignocellulose and cellulose and caused upregulation of genes coding associated enzymatic machinery including carbohydrate binding modules in family 18 and dockerin domains across multiple growth substrates relative to C. churrovis monoculture. Two other fungal strains grown on a reed canary grass substrate in co-culture with the same methanogen also exhibited high log2-fold change values for upregulation of genes encoding carbohydrate binding modules in families 1 and 18. Transcriptional upregulation indicated that co-culture of the C. churrovis strain with a methanogen may enhance pyruvate formate lyase (PFL) function for growth on xylan and fructose and production of bottleneck enzymes in sugar utilization pathways, further supporting the hypothesis that co-culture with a methanogen may enhance certain fungal metabolic functions. Upregulation of CBM18 may play a role in fungal–methanogen physical associations and fungal cell wall development and remodeling.

OBJECTIVES/GOALS: Despite the importance of stakeholder engagement in research, there remains a critical need for methods that facilitate the engagement of diverse stakeholders throughout the research process. We describe dissemination and capacity building for the SEED Method, which was created to involve stakeholders in the research development process. METHODS/STUDY POPULATION: In order to raise greater awareness of the SEED Method and to build capacity among research teams, we received funding from the Patient-Centered Outcomes Research Institute (PCORI) for a 2-year project to implement a plan of outreach, training, interactive learning, and technical assistance, as well as an innovative partnership with the Extension Foundation. Tools created for this project include an internet site providing tools and materials, live and on-demand webinars, training videos, SEED materials, a blog, and an interactive course/toolkit. In addition, we created a monthly learning collaborative and provided direct technical assistance to teams using the SEED Method in their research engagement projects. We evaluated user satisfaction with the tools and support provided through online surveys. RESULTS/ANTICIPATED RESULTS: We highlight the routes to reaching potential users and diverse approaches to capacity building, including multi-media training materials, interactive learning sessions, and customized technical assistance. As a result of outreach and capacity building, there are currently 13 research teams using the SEED Method to engage stakeholders in research development across various topics. We link this result to the dissemination and capacity building strategies utilized and the paths through which teams learned about the SEED Method. We also look at how the teams are using the method in terms of project goals and approaches to adapting the SEED Toolkit. DISCUSSION/SIGNIFICANCE: The use of PHR continues to increase, and with it the emergence of new approaches to involve patients, stakeholders, and communities. Innovations in engagement need to reach potential users and build capacity among researchers and communities.

The Mentawai archipelago is situated to the west of mainland Sumatra and is part of the West Sumatra province. The Mentawai people are indigenous to this archipelago and are well known for their traditional healing practices performed by their Sikerei healers. Only a few studies on the traditional plant medicines of the Mentawai people have been published, which mostly suggest that Zingiberaceae is one of the most widely used families. This study examines the indigenous knowledge of Zingiberaceae by the Mentawai people living in Siberut. Field surveys were undertaken at four locations in the island where the Sikerei healers were interviewed directly to obtain information about medicinal treatments using plants from the Zingiberaceae family. Voucher specimens were collected, dried and deposited at the Herbarium of Andalas University (ANDA), Padang, West Sumatra. The study suggests that at least 32 Zingiberaceae species are used in the Mentawai’s traditional medicines. The floristic aspects, the plant part used, and the type of disease treated are discussed.

Background Primary care staff do not provide consistent education on musculoskeletal pain management to patients in accordance with the recommendations of clinical practice guidelines. We have developed a concise online learning program to bridge this gap. Objectives To investigate (1) the effectiveness of 1-hour musculoskeletal pain neurophysiology education program conducted by a physiotherapist on primary care staff; (2) the correlation between demographic factors of staff and the interdisciplinary learning performances. Methods We piloted a multicenter single-blind prospective study on sixty-four staff from the pharmacy department in eight public primary care clinics. Participants in the intervention group attended the 1-hour online program compared to a control group. The Neurophysiology of Pain Questionnaire (NPQ) to assess learning and the 10-point Likert scale program evaluation form to assess learning reaction of participants after the program were used. Results The participants reacted positively to the online learning program. The intervention group significantly improved in their musculoskeletal pain knowledge by a greater mean NPQ score difference 2.39 ( p < 0.001) compared with the control group. There were poor correlations between the demographic factors and their learning. Conclusion The pilot study shows that primary care staff may still utilize a biomedical approach in managing musculoskeletal pain. The improvement in knowledge demonstrates that short online programs could be a valuable part of interdisciplinary education in primary care because it is easily accessible by healthcare professionals and can benefit other healthcare staff regardless of their background.

Questions: What perceptions do physiotherapists have about their role in managing the physical health of people with severe and persistent mental illness (SPMI)? What are the barriers to treating physical health conditions in this clinical population, and what enablers may improve access to physiotherapy services? Design: Mixed-methods research design combining focus groups, interviews and an online survey. Participants: Eighty-eight Australian registered physiotherapists: 31 in the focus groups and interviews (mean age 32 years, 68% female) and 57 in the survey (mean age 38 years, 86% female). Methods: Focus groups and interviews explored participants' understanding of mental illness; their role in managing the physical health of people with SPMI; and the barriers and enablers to service delivery. Key themes were derived using an inductive approach. The survey was used to determine physiotherapists' attitudes and knowledge regarding mental illness; perceived role of physiotherapy in mental health; and need for professional development in the mental health area. Participant characteristics and survey information were analysed using descriptive statistics. Results: Qualitative and quantitative results were confirmatory. Participants indicated that physiotherapists can play a role in the management of physical health conditions in people with SPMI. Participants also stated that such treatment was part of their job, given the extensive evidence that physiotherapy interventions are effective for the comorbidities that are common among people with SPMI. Barriers included: limited education about and confidence in how to manage people with SPMI; health system structure; and stigmatisation of people with SPMI. Conclusion: Physiotherapists are ideally poised to become leaders in managing the physical health of people with SPMI. To improve the physical health in this important yet overlooked population, it is recommended that: physiotherapists take up general mental health training opportunities; undergraduate physiotherapy education increases content in this clinical area; physiotherapy-specific professional development opportunities are developed further; and health system barriers are addressed. Key words: Physiotherapy, Physical therapy, Severe mental illness, Mental health, Physical activity

Background: Biobanking of Mycobacterium tuberculosis (Mtb) sputum samples for future research activities recommends the use of −70°C or −80°C freezers. Infrastructure for biobanking is not readily available in the majority of low-income countries. This study aimed to assess the recovery rate of Mtb isolates stored at room temperature for more than 6 years in Zimbabwe. Methods: Census samples of all confirmed rifampicin-resistant/multidrug-resistant tuberculosis isolates that were stored in mycobacterial growth indicator tubes (MGITs) at room temperature from 2011 to 2016 were identified and retrieved. The samples were subcultured on MGIT and 7H10 solid media for the extraction of genomic deoxyribonucleic acid using the phenol/chloroform method followed by precipitation with isopropanol. Results: A total of 248/400 (62%) isolates were successfully recovered. Recovery rates increased with declining time since the last culture, with 51% for samples stored for 6 years which increased to 77% for those stored for 1 year. The isolates that grew but were contaminated during the first subculture at the National Microbiology Reference Laboratory in Harare could not be recovered through decontamination because of limited resources. Decontamination was only possible during the second culture at the University of Stellenbosch. Conclusion: Storage of Mtb isolates at room temperature is a viable option in low-income countries where currently recommended biobanking procedures may not be available. This low-cost biobanking will facilitate research activities years later as new questions arise. Standard infection prevention and control when handling Mtb samples stored under room temperature for long periods is strongly recommended as these bacteria remain viable longer than previously reported.

We present a 14-year-old boy with peritoneal epithelial malignant mesothelioma (PEMM). While pathology is required to make this diagnosis, radiology plays a crucial role throughout the clinical course of this disease. The key imaging characteristics of peritoneal mesothelioma have been previously well-described in the adult population, but there are rare reports in the pediatric population. This pediatric report highlights the multidimensional use of imaging in this disease, from the initial evaluation to therapeutic supplementation and subsequent follow-up.

Within the field of occupational therapy, the issue of transitioning from an entry-level master's degree to an entry-level doctorate degree is under debate. As such, it is important to investigate the impact of the transition in order to help make educated decisions about the potential future of the profession.This study analyzed retrospective data collected from six cohorts at one Midwestern university to analyze the impact of the transition to an entry-level doctorate on diversity, admission and matriculation rates, and fieldwork reservations. No statistical difference in diversity between masters and doctorate level cohorts was found but it is of note that it approached significance (χ2 (1) = 3.32, p = 0.07). There was a slight decrease in number of total students that applied to the program (7.75%) and the number of fieldwork reservations (5.23%), however this was accounted for by a 60% increase in occupational therapy programs in the state the study took place. Results of this study provide preliminary data of how one university has succeeded in the transition to an entry-level doctorate and can be used to inform other programs as they consider this transition.

Rationale: Consensus guidelines on the management of methotrexate-induced nephrotoxicity using glucarpidase (Voraxaze) may be relatively unfamiliar to the nephrology community. Presenting concerns of the patient: A 61-year-old man with intravascular large B-cell lymphoma was admitted for cycle #1 of high-dose methotrexate (HDMTX) following 2 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. On admission, he was clinically euvolemic and had a creatinine clearance of 98 mL/min. He received standard HDMTX toxicity prophylaxis with volume expansion, urinary alkalinization, and leucovorin rescue. Diagnoses: Despite prophylactic efforts, he developed a severe acute kidney injury, creatinine 63 to 226 µmol/L (2.56 mg/dL), following HDMTX, impaired methotrexate clearance, and neurotoxicity manifested by status epilepticus. Interventions: He was given glucarpidase to convert extracellular methotrexate into its inactive metabolites, glutamate and DAMPA (4-deoxy-4-amino- N 10 -methylpteroic acid) at 52 hours post-HDMTX. Cross-reactivity between commercial methotrexate immunoassays with DAMPA led to falsely elevated methotrexate concentrations for much longer than expected based on the current guideline (5 days instead of

The main objectives of the Nepal National Mammal Red Data Book (RDB) were to provide comprehensive and up-to-date accounts of 212 mammal species recorded in Nepal, assess their status applying the IUCN Guidelines at Regional Levels, identify threats and recommend the most practical measures for their conservation. It is hoped that the Mammal RDB will help Nepal achieve the Convention on Biological Diversity target of preventing the extinction of known threatened species and improving their conservation status. Of the 212 mammal species assessed, 49 species (23%) were listed as nationally threatened. These comprise nine (18%) Critically Endangered species, 26 (53%) Endangered species and 14 (29%) Vulnerable species. One species was considered regionally Extinct. A total of seven species (3%) were considered Near Threatened and 83 species (39%) were Data Deficient. Over sixty percent of Nepal’s ungulates are threatened and almost half of Nepal’s carnivores face extinction (45% threatened). Bats and small mammals are the least known groups with 60 species being Data Deficient. Habitat loss, degradation and fragmentation are the most significant threats. Other significant threats include illegal hunting, small and fragmented populations, reduction of prey base, human wildlife conflict and persecution, climate change, invasive species, disease and inadequate knowledge and research. Adequate measures to address these threats are described. It was also concluded that re-assessments of the status of certain mammal groups be carried out every five years and the setting up of a national online species database and mapping system would also greatly help in land-use planning and policies.

Background: Young children living in urban slums are vulnerable to malnutrition and subsequently poor health outcomes, but data on the correlates of stunting, underweight, wasting, and anemia specifically among 10–18 month-old children in India remain limited.Objective: In this analysis, we sought to describe the prevalence of and examine correlates for different markers of undernutrition, including stunting, underweight, and anemia among 10–18 month-old children living in urban slums, an understudied vulnerable group.Methods: Children and their mothers (n = 323) were screened for anthropometry, demographics, and complete blood counts for hemoglobin concentration between March and November 2017 (Clinicaltrials.gov ID: NCT02233764). Correlates included child and mother's age, sex, birth order, birth weight, illness episodes, hemoglobin concentration, family income, maternal height, and maternal education level. Risk ratios (RR, 95% CI) for binary outcomes (stunting, underweight, wasting and anemia) and mean differences (β, 95% CI) for continuous outcomes (anthropometric Z-scores, hemoglobin concentration) were calculated using multivariate binomial and linear regression (SAS 9.4).Results: The prevalence of stunting was 31.2%, underweight 25.1%, wasting (9.0%), and anemia (76%) among all children. Male children had a higher prevalence of poor growth indices and lower anthropometric Z-scores than females. Male sex, low birthweight, shorter maternal height, report of ≥1 episodes of illness within the past month, older maternal age, and birth order ≥2 were also associated with poor growth and anemia in multivariate models. Correlates of undernutrition were different among females and males. Female children had a 40% (20, 60%) higher risk of anemia associated with diarrhea, and male children who were firstborn had a 20% (0, 70%) lower risk of anemia.Conclusions: These results show that poor growth and anemia among young children is prevalent in urban slums of Mumbai, and that sex of the child may play an important role in informing interventions to address undernutrition.

The CRISPR/Cas9 system is an RNA guided nuclease system that evolved as a mechanism of adaptive immunity in bacteria. This system has been adopted for numerous genome engineering applications in research and recently, therapeutics. The CRISPR/Cas9 system has been largely implemented by delivery of Cas9 as protein, RNA, or plasmid along with a chimeric crRNA-tracrRNA guide RNA (gRNA) under the expression of a pol III promoter, such as U6. Using this approach, multiplex genome engineering has been achieved by delivering several U6-gRNA plasmids targeting multiple loci. However, this approach is limited due to the efficiently of delivering multiple plasmids to a single cell at one time. To augment the capability and accessibility of multiplexed genome engineering, we developed an efficient golden gate based method to assemble gRNAs linked by optimal Csy4 ribonuclease sequences to deliver up to 10 gRNAs as a single gRNA array transcript. Here we report the optimal expression of our guide RNA array under a strong pol II promoter. This system can be implemented alongside the myriad of CRISPR applications, allowing users to model complex biological processes requiring numerous gRNAs.

Biofortification, a method for increasing micronutrient content of staple crops, is a promising strategy for combating major global health problems, such as iron and zinc deficiency. We examined the acceptability of recipes prepared using iron- and zinc-biofortified pearl millet (FeZnPM) (~80 ppm Fe, ~34 ppm Zn, varietal ICTP-8203), compared to conventional pearl millet (CPM) (~20 ppm Fe, ~19 ppm Zn) in preparation for an efficacy trial. Our objective was to examine the acceptability of FeZnPM compared to CPM among young children and mothers living in the urban slums of Mumbai. Standardized traditional feeding program recipes (n = 18) were prepared with either FeZnPM or CPM flour. The weight (g) of each food product was measured before and after consumption by children (n = 125) and the average grams consumed over a 3-day period were recorded. Mothers (n = 60) rated recipes using a 9-point hedonic scale. Mean intakes and hedonic scores of each food product were compared using t-tests across the two types of pearl millet. There were no statistically significant differences in consumption by children (FeZnPM: 25.27 ± 13.0 g; CPM: 21.72 ± 6.90 g) across the food products (P = 0.28). Overall mean hedonic scores for all recipes were between 7 to 9 points. CPM products were rated higher overall (8.22 ± 0.28) compared to FeZnPM products (7.95 ± 0.35) (P = 0.01). FeZnPM and CPM were similarly consumed and had high hedonic scores, demonstrating high acceptability in this population. These results support using these varieties of pearl millet in a proposed trial [http://Clinicaltrials.gov ID: NCT02233764; Clinical Trials Registry of India (CTRI), reference number REF/2014/10/007731, CTRI number CTRI/2015/11/006376] testing the efficacy of FeZnPM for improving iron status and growth.

Objective: Cervical cancer is a leading cause of cancer mortality in South Africa. However, little is known about oral HPV infection in high HIV seroprevalence settings. Method: 34 adult heterosexual couples attending an HIV testing center in Soweto, South Africa were enrolled. Each participant provided an oral rinse sample and genital swab, which were tested for 37 types of HPV DNA, and completed a risk behavior survey. Results: Median age was 31 years and 9% (3/34) of men and 29% (10/34) of women enrolled tested HIV-positive; median CD4 count was 437cells/mm3. Oral HPV prevalence was similar in women and men (12% vs 18%, p=0.48), and was non-significantly higher in HIV-infected vs. HIV-uninfected (23% vs. 13%, p=0.34) subjects. Most men (82%) and women (84%) reported ever performing oral sex. Median number of lifetime sexual partners was 2-5while median number of lifetime oral sex partners was 1. Oncogenic HPV subtypes were detected in 4% of oral, 26% of penile, and 74% of vaginal samples, including HPV16 in 1%, 12%, and 21% of these samples respectively. Genital HPV prevalence was significantly higher than oral HPV prevalence (75% vs. 15%, p=

The mechanism of association of hypopigmentation and sensorial loss in a leprosy macular lesions has not been clarified yet. The biopsy of a macular lesion on the medial face of the right forearm of a fourteen-year old male leprosy patient was submitted to DOPA-staining for melanocytes, which is specific for the melanocytic tyrosinase enzyme and it is a proper method for identifying and counting these cells in the skin. A contralateral specimen of the same patient went through the same procedure as a control experiment. The specimen from the macular lesion showed a higher number of DOPA-stained melanocytes than the control fragment. Dermal melanocytes were present in high amounts in the abnormal specimen. Increased expression of tyrosinase by melanocytes in the macular lesions may reflect a positive feed-back stimulus represented by the lack of substrate tyrosine, which may in turn be utilized by the mycobacterial agent. Ultrastructural study of the normal and pathological specimens showed no significant differences in the morphological appearance of melanocytes and their melanosomes. These results suggest that the utilization of phenolic compound by the Mycobacterium leprae may be involved in the mechanism of hypopigmentation. A higher number of cases will be necessary to confirm this hypothesis.

Introduction: Cannabis products have been used in the management of headaches in adults and may play a role in pediatric chronic pain. Canadian pediatricians report increasing use of cannabis for the management of chronic headaches, despite no well-controlled studies to inform its dosing, safety, and effectiveness. The aim of our clinical trial is to determine the dosing and safety of a Cannabidiol (CBD)-enriched Cannabis Herbal Extract (CHE) for the treatment of chronic headaches in adolescents. Methods and analysis: Youth, parents, and an expert steering committee co-designed this tolerability study. Twenty adolescents (aged 14 to 17 years), with a chronic migraine diagnosis for more than 6 months that has not responded to other therapies will be enrolled into an open label, dose escalation study across three Canadian sites. Study participants will receive escalating doses of a CBD-enriched CHE (MPL-001 with a THC:CBD of 1:25), starting at 0.2–0.4 mg/kg of CBD per day and escalating monthly up to 0.8–1.0 mg/kg of CBD per day. The primary objective of this study is to determine the safety and tolerability of CBD-enriched CHE in adolescents with chronic migraine. Secondary objectives of this study will inform the development of subsequent randomized controlled trials and include investigating the relationship between the dose escalation and change in the frequency of headache, impact and intensity of pain, changes in sleep, mood, function, and quality of life. Exploratory outcomes include investigating steady-state trough plasma levels of bioactive cannabinoids and investigating how pharmacogenetic profiles affect cannabinoid metabolism among adolescents receiving CBD-enriched CHE. Discussion: This protocol was co-designed with youth and describes a tolerability clinical trial of CBD-enriched CHE in adolescents with chronic headaches that have not responded to conventional therapies. This study is the first clinical trial on cannabis products in adolescents with chronic headaches and will inform the development of future comparative effectiveness clinical trials. Trial registration: CAN-CHA trial is registered with ClinicalTrials.gov with a number of register NCT05337033. [ABSTRACT FROM AUTHOR]