Genomic Analysis Aids in the Management of Dermoscopically Atypical Pigmented Lesions.

BACKGROUND: Numerous melanoma-specific dermoscopic features have been described in invasive melanomas, while fewer features are found in melanoma in situ (MIS) and atypical nevi (ATN). Consensus regarding which features are critical for the differentiation of MIS from ATN has not been reached. PURPOSE: Determine 1) whether there are dermoscopic features that differentiate early MIS from ATN, and 2) whether non-invasive assessment of genomic biomarkers (LINC00518 and PRAME) can aid in patient management. METHODS: From 2018 to 2023, 56 melanomas were evaluated for 5 clinical and 13 dermoscopic features and melanoma-associated genomic biomarkers. Two groups of ATN with positive and negative genomic biomarkers were randomly selected for comparison. RESULTS: All melanomas in this study expressed one or both melanoma-associated genomic markers. MIS had an average of 3.90 (range, 2-7) of the 13 dermoscopic features, while invasive melanomas had an average of 4.44 (range, 3-6). Sixteen of 40 (40%) MIS and 3 of 16 (18.8%) invasive melanomas had 3 or fewer dermoscopic features. These findings were comparable to those observed in both ATN groups. The most common dermoscopic features were absent or diminished pigment network, regression structures, and granularity. This combination of features was most helpful in identifying lesions for genomic testing. CONCLUSIONS: Clinical and dermoscopic features alone could not differentiate MIS from ATN. Non-invasive genomic testing helped differentiate lower from higher-risk lesions and aid in clinical management decisions. Genomic testing was particularly helpful in patients with large numbers of lesions with several being considered for biopsy based on clinical and dermoscopic examination. J Drugs Dermatol. 2024;23(9):717-723. doi:10.36849/JDD.8454.

Data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries: developing and piloting an assessment tool (VPASS).

BACKGROUND: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to pilot this tool in sites using MNCH data collection systems through virtual informant interviews. METHODS: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to pilot domains included in the assessment tool. RESULTS: We developed and piloted the "VPASS (Vaccines during Pregnancy - sites supporting Active Safety Surveillance) assessment tool" through interviews with nine stakeholders, including central-level systems key informants and site-level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). The tool includes different domains such as the system's purpose, the scale of implementation, data capture and confidentiality, type of data collected, the capability of integration with other platforms, data management policies and data quality monitoring. Similarities among sites were found regarding some domains, such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy, such as a routine collection of MNCH individual data and the capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR). CONCLUSION: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by identifying and using active individual MNCH data collection systems in LMICs.

Early Evidence Indicates Vitamin D Improves Symptoms of Irritable Bowel Syndrome: Nursing Implications and Future Research Opportunities.

Irritable bowel syndrome (IBS) affects approximately 11.2% of the population. Yet, full understanding of its etiology and optimal treatment remains elusive. Understanding of the underlying pathophysiology of IBS has been limited. However, research is beginning to identify the cause as multifactorial (e.g., low-grade local mucosal inflammation, systemic immune activation, altered intestinal permeability, intestinal hypersensitivity, altered central nervous system processing, changes in intestinal microbiota). Understanding of the role of vitamin D in intestinal inflammation, immunity, and gastrointestinal conditions is increasing but is not yet fully understood. Growing evidence has linked vitamin D deficiency with a variety of gastrointestinal disorders, including inflammatory bowel disease, diverticulitis, colorectal cancer, and IBS. Several studies have demonstrated that individuals with IBS are more likely to have vitamin D deficiency than healthy controls. Recent vitamin D supplementation studies have shown improvement in quality of life and reduction in IBS symptoms (including abdominal pain, distention, flatulence, constipation, and visceral sensitivity) but the mechanism remains unclear. Nurses are well positioned to educate patients about the importance of sufficient vitamin D for overall health in individuals with IBS as well as participate in well-designed therapeutic studies to explore whether enhanced vitamin D status will ultimately help treat IBS more effectively.

The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission.

BACKGROUND: The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016. OBJECTIVE: Among thunderstorm-affected patients presenting to emergency rooms (ERs), we investigated risk factors predicting severe attacks requiring admission to hospital. METHODS: Thunderstorm-affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed. RESULTS: We interviewed 1435/2248 (64%) of thunderstorm-affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [aOR] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission (aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non-Asian patients (aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia (OR = 5.42, 95% CI 1.56, 18.83). CONCLUSIONS: In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions.

The use of whole blood in US military operations in Iraq, Syria, and Afghanistan since the introduction of low-titer Type O whole blood: feasibility, acceptability, challenges.

BACKGROUND: Hemorrhage is the leading cause of preventable death in military and civilian traumatic injury. Blood product resuscitation improves survival. Low-titer Type O Whole Blood (LTOWB) was recently re-introduced to the combat theater as a universal resuscitation product for hemorrhagic shock. This study assessed the utilization patterns of LTOWB compared to warm fresh whole blood (WFWB) and blood component therapy (CT) in US Military Operations in Iraq/Syria and Afghanistan known as Operation Inherent Resolve (OIR) and Operation Freedom's Sentinel (OFS) respectively. We hypothesized LTOWB utilization would increase over time given its advantages. STUDY DESIGN AND METHODS: Using the Theater Medical Data Store, patients receiving blood products between January 2016 and December 2017 were identified. Product utilization ratios (PUR) for LTOWB, WFWB, and CT were compared across Area of Operations (AORs), medical treatment facilities (Role 2 vs. Role 3), and time. PUR was defined as number of blood products transfused/(number of blood products transfused + number of blood products wasted). RESULTS: The overall PUR for all blood products was 17.4%; the LTOWB PUR was 14.3%. Over the study period, the total number of blood products transfused increased 133%. Although the total whole blood (WB) increased from 2.1% to 6.6% of all products transfused, WFWB use remained at 2% while LTOWB transfusions increased from 0.5% to 4%. Transfusion of LTOWB occurred more in austere Role 2 facilities compared to Role 3 hospitals. CONCLUSIONS: LTOWB transfusion is feasible in austere, far-forward environments. Further investigation is needed regarding the safety, clinical outcomes, and drivers of LTOWB transfusions.

Catalytic Determinants of Alkene Production by the Cytochrome P450 Peroxygenase OleTJE.

The Jeotgalicoccus sp. peroxygenase cytochrome P450 OleTJE (CYP152L1) is a hydrogen peroxide-driven oxidase that catalyzes oxidative decarboxylation of fatty acids, producing terminal alkenes with applications as fine chemicals and biofuels. Understanding mechanisms that favor decarboxylation over fatty acid hydroxylation in OleTJE could enable protein engineering to improve catalysis or to introduce decarboxylation activity into P450s with different substrate preferences. In this manuscript, we have focused on OleTJE active site residues Phe79, His85, and Arg245 to interrogate their roles in substrate binding and catalytic activity. His85 is a potential proton donor to reactive iron-oxo species during substrate decarboxylation. The H85Q mutant substitutes a glutamine found in several peroxygenases that favor fatty acid hydroxylation. H85Q OleTJE still favors alkene production, suggesting alternative protonation mechanisms. However, the mutant undergoes only minor substrate binding-induced heme iron spin state shift toward high spin by comparison with WT OleTJE, indicating the key role of His85 in this process. Phe79 interacts with His85, and Phe79 mutants showed diminished affinity for shorter chain (C10-C16) fatty acids and weak substrate-induced high spin conversion. F79A OleTJE is least affected in substrate oxidation, whereas the F79W/Y mutants exhibit lower stability and cysteine thiolate protonation on reduction. Finally, Arg245 is crucial for binding the substrate carboxylate, and R245E/L mutations severely compromise activity and heme content, although alkene products are formed from some substrates, including stearic acid (C18:0). The results identify crucial roles for the active site amino acid trio in determining OleTJE catalytic efficiency in alkene production and in regulating protein stability, heme iron coordination, and spin state.

Structure and biochemical properties of the alkene producing cytochrome P450 OleTJE (CYP152L1) from the Jeotgalicoccus sp. 8456 bacterium.

The production of hydrocarbons in nature has been documented for only a limited set of organisms, with many of the molecular components underpinning these processes only recently identified. There is an obvious scope for application of these catalysts and engineered variants thereof in the future production of biofuels. Here we present biochemical characterization and crystal structures of a cytochrome P450 fatty acid peroxygenase: the terminal alkene forming OleTJE (CYP152L1) from Jeotgalicoccus sp. 8456. OleTJE is stabilized at high ionic strength, but aggregation and precipitation of OleTJE in low salt buffer can be turned to advantage for purification, because resolubilized OleTJE is fully active and extensively dissociated from lipids. OleTJE binds avidly to a range of long chain fatty acids, and structures of both ligand-free and arachidic acid-bound OleTJE reveal that the P450 active site is preformed for fatty acid binding. OleTJE heme iron has an unusually positive redox potential (-103 mV versus normal hydrogen electrode), which is not significantly affected by substrate binding, despite extensive conversion of the heme iron to a high spin ferric state. Terminal alkenes are produced from a range of saturated fatty acids (C12-C20), and stopped-flow spectroscopy indicates a rapid reaction between peroxide and fatty acid-bound OleTJE (167 s(-1) at 200 µm H2O2). Surprisingly, the active site is highly similar in structure to the related P450BSß, which catalyzes hydroxylation of fatty acids as opposed to decarboxylation. Our data provide new insights into structural and mechanistic properties of a robust P450 with potential industrial applications.

Single-molecule in vivo imaging of bacterial respiratory complexes indicates delocalized oxidative phosphorylation.

Chemiosmotic energy coupling through oxidative phosphorylation (OXPHOS) is crucial to life, requiring coordinated enzymes whose membrane organization and dynamics are poorly understood. We quantitatively explore localization, stoichiometry, and dynamics of key OXPHOS complexes, functionally fluorescent protein-tagged, in Escherichia coli using low-angle fluorescence and superresolution microscopy, applying single-molecule analysis and novel nanoscale co-localization measurements. Mobile 100-200nm membrane domains containing tens to hundreds of complexes are indicated. Central to our results is that domains of different functional OXPHOS complexes do not co-localize, but ubiquinone diffusion in the membrane is rapid and long-range, consistent with a mobile carrier shuttling electrons between islands of different complexes. Our results categorically demonstrate that electron transport and proton circuitry in this model bacterium are spatially delocalized over the cell membrane, in stark contrast to mitochondrial bioenergetic supercomplexes. Different organisms use radically different strategies for OXPHOS membrane organization, likely depending on the stability of their environment.

Use of Surveillance Systems in Detection of a Ciguatera Fish Poisoning Outbreak - Orange County, Florida, 2014.

What is already known on this topic? Ciguatera fish poisoning (CFP), caused by the ingestion of predatory reef-dwelling fish harboring ciguatoxins is one of the most commonly reported fish-associated marine intoxications. Ciguatoxin retains toxicity regardless of freezing or cooking. Prompt treatment can reduce debilitating neurologic symptoms that are associated with CFP.What is added by this report? Syndromic surveillance systems in Florida identified six adults with CFP following consumption of black grouper. Five patients sought medical attention; health care providers did not make a diagnosis of CFP or report the cases to public health authorities, and none of the patients received treatment. Close collaboration among several investigating agencies allowed traceback efforts to link black grouper consumed by all patients to a common international distributor.What are the implications for public health practice? Syndromic surveillance systems capable of detecting CFP are essential public health tools to identify outbreaks and enhance investigations. Medical and public health practitioners should be educated to inquire about recent fish consumption when evaluating patients with clinically compatible signs and symptoms to allow for prompt treatment, and report suspected CFP cases to public health authorities to facilitate source-food traceback efforts. Public education on avoidance of consumption of relatively large predatory reef fish species known to be from ciguatoxic-endemic areas might reduce the risk for CFP.

First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.

Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.

Approaches for measuring cumulative childhood adversity: A study of youth from 5 sub-Saharan African countries.

BACKGROUND: Adverse childhood experiences (ACEs) include forms of abuse, neglect, and household stressors that are potentially early life traumatic experiences. A summed integer count of ACEs is often used to examine cumulative childhood adversity (CCA) but has limitations. OBJECTIVES: The current study tests two additional methods for measuring CCA using large samples of youth in low- and middle-income countries. PARTICIPANTS AND SETTING: Pooled data were analyzed from a multi-country, nationally representative sample of youth aged 18-24 years (N = 11,498) who completed the Violence Against Children and Youth Surveys (VACS) in Lesotho, Cote d'Ivoire, Kenya, Namibia, and Mozambique. METHODS: ACE exposures included: physical, sexual, and emotional violence; witnessing interparental violence; witnessing community violence; orphanhood. CCA was operationalized using an ACE score, ACE impact (standardized regression coefficients from outcome severity), and ACE exposure context (household; intimate partner; peer; community). Associations between CCA with mental distress (MD) were examined by sex using p ≤ 0.05 as the significance level. RESULTS: Exposure to ≥3 ACEs was associated with MD (p < 0.05) for both sexes. Among females, all contexts contributed to MD except peer ACEs (p < 0.05). Among males, household and community ACEs contributed to MD. High-impact ACEs were associated with MD both sexes. ACE context was the best-fitting model for these data. CONCLUSIONS: The challenges operationalizing CCA warrant continued research to ensure adversity type, severity, and context lead to validly assessing ACEs impact on child wellbeing.

Parenting-related positive childhood experiences, adverse childhood experiences, and mental health-Four sub-Saharan African countries.

BACKGROUND: Adverse Childhood Experiences (ACEs) are associated with poor mental health outcomes and risk-taking behaviors. Positive childhood experiences (PCEs) may mitigate these negative impacts. OBJECTIVE: This study 1) assessed the associations between ACEs and negative health outcomes and risk-taking behaviors among young adults, and 2) evaluated whether - and which - PCEs moderate the association between ACEs and these outcomes in sub-Saharan Africa. METHODS: This multi-country analysis combined cross-sectional representative survey data from young adults, ages 18-24 years, from the 2019 Kenya, 2018 Lesotho, 2019 Mozambique, and 2019 Namibia Violence Against Children and Youth Surveys. The association between experiencing any ACEs and each health outcome was assessed using Wald's chi-square tests. Multivariable logistic regression analyses assessed the association between each PCE and each outcome of interest. RESULTS: Females who experienced any ACEs had higher odds of experiencing moderate to severe mental distress (aOR = 2.7, 95%CI: 1.9, 3.9). Males who experienced any ACEs had higher odds of experiencing suicidal/self-harm behaviors (aOR = 6.7, 95%CI: 2.8, 16.0) and substance use (aOR = 2.5, 95%CI: 1.4, 4.2). In females, strong mother-child relationship was protective against moderate to severe mental distress (aOR = 0.7, 95%CI: 0.6, 0.9), suicidal/self-harm behaviors (aOR = 0.6, 95%CI: 0.4, 0.9), and substance use (aOR = 0.6, 95%CI: 0.4, 0.9). For males, a strong mother-child relationship was protective against suicidal/self-harm behaviors (aOR = 0.5, 95%CI: 0.2, 0.9), and a strong father-child relationship was protective against suicidal/self-harm behaviors (aOR = 0.4, 95%CI: 0.2, 0.7) and substance use (aOR = 0.6, 95%CI: 0.4, 0.8). CONCLUSIONS: Strong parenting programs may likely play an important role in improving the psychosocial health of young adults.

Service-seeking behaviors among male victims of violence in five African countries: The effects of positive and adverse childhood experiences.

BACKGROUND: Violence against boys and men is widely under-reported. Boys and men face unique and gendered barriers to accessing services following experiences of violence. PARTICIPANTS AND SETTING: The study is a secondary data analysis of five nationally representative population-based Violence Against Children and Youth Surveys (VACS) conducted in Kenya (2019), Côte d'Ivoire (2018), Lesotho (2018), Mozambique (2019), and Namibia (2019). Analysis was limited to males between 18 and 24 years who experienced lifetime physical or sexual violence. OBJECTIVE AND METHODS: We analyzed the association between positive and adverse childhood experiences (PCEs and ACEs), and seeking post-violence services among males using bivariate chi-squared tests and multivariable logistic regression. RESULTS: 8.02 % (5.55-10.50 %) of male victims between the ages of 18 and 24 sought services for any lifetime physical or sexual violence. Witnessing interparental violence and experiencing death of one or both parents were each associated with increased odds of having sought post-violence services (aOR 2.43; 95 % CI: 1.25-4.79; aOR 2.27; 95 % CI: 1.14-4.50), controlling for education, violence frequency, and violence type. High parental monitoring was associated with increased odds of service seeking (aOR 1.79; 95 % CI: 1.02-3.16), while strong father-child relationship was associated with lower odds (aOR 0.45; 95 % CI: 0.23-0.89). CONCLUSION: These findings contribute to limited research on service-seeking behaviors among men and boys. While some parent-youth relationship factors were associated with higher odds of service-seeking, the outcome remained rare. Age and gender-related barriers should be addressed where post-violence care services are offered.

Parental absence as an adverse childhood experience among young adults in sub-Saharan Africa.

BACKGROUND: Parental absence in childhood has been associated with multiple negative consequences, such as depression and anxiety in young adulthood. OBJECTIVE: To assess whether parental absence for six months or more in childhood is associated with poor mental health and substance use in young adulthood and whether parental absence accounts for additional variance beyond those explained by other adverse childhood experiences (ACEs) among youth in sub-Saharan Africa. PARTICIPANTS AND SETTINGS: We used combined Violence Against Children and Youth Survey (VACS) data from Cote d'Ivoire (2018), Lesotho (2018), Kenya (2019), Namibia (2019), and Mozambique (2019). Analyses were restricted to 18-24-year-olds (nf = 7699; nm = 2482). METHODS: We used logistic regression to examine sex-stratified relationships between parental absence in childhood (defined as biological mother or father being away for six months or more before age 18) and mental health problems and substance use and whether parental absence explained additional variance beyond those explained by other ACEs. RESULTS: In sub-Saharan Africa, parental absence in childhood was common (30.5 % in females and 25.1 % in males), significantly associated with poor mental health and substance use among females and males and accounted for additional variance beyond those explained by conventional ACEs. For example, after controlling for study covariates and other ACEs, females who experienced any parental absence had 1.52 (95 % CI = 1.02-2.26) higher odds of experiencing moderate/serious psychological distress compared with those who did not. CONCLUSION: The observed association between parental absence and poor mental health suggests that this experience has significant adverse consequences and merits consideration as an ACE.

Modeling Behavior and Vaccine Hesitancy Using Twitter-Derived US Population Sentiment during the COVID-19 Pandemic to Predict Daily Vaccination Inoculations.

The sentiment analysis of social media for predicting behavior during a pandemic is seminal in nature. As an applied contribution, we present sentiment-based regression models for predicting the United States COVID-19 first dose, second dose, and booster daily inoculations from 1 June 2021 to 31 March 2022. The models merge independent variables representing fear of the virus and vaccine hesitancy. Large correlations exceeding 77% and 84% for the first-dose and booster-dose models inspire confidence in the merger of the independent variables. Death count as a traditional measure of fear is a lagging indicator of inoculations, while Twitter-positive and -negative tweets are strong predictors of inoculations. Thus, the use of sentiment analysis for predicting inoculations is strongly supported with administrative events being catalysts for tweets. Non-inclusion in the second-dose regression model of data occurring before the 1 June 2021 timeframe appear to limit the second-dose model results-only achieving a moderate correlation exceeding 53%. Limiting tweet collection to geolocated tweets does not encompass the entire US Twitter population. Nonetheless, results from Kaiser Family Foundation (KFF) surveys appear to generally support the regression factors common to the first-dose and booster-dose regression models and their results.

Coding definitions of participant religious, non-religious and spiritual beliefs in the Avon Longitudinal Study of Parents & Children (ALSPAC).

Mainstream religious beliefs and behaviours have been shown to have positive effects on health and well-being, but there has been increasing secularisation in the West over time. With concurrent increases in those stating they have no religion (the 'nones') there are increasing numbers now describing themselves as humanist, 'spiritual but not religious' or who have sought alternative forms of belief. Others have formed their own beliefs using elements of different belief systems. This trend is reflected in ALSPAC data with larger proportions considering themselves as 'nones', agnostic or atheist, and about 3% of parent participants consistently stating they had 'other' beliefs. The main aim of this paper is to describe the coding of the Christian denominations, world religions, non-mainstream beliefs (NMB) and non-religious groups derived from the text-based data collected from the original mother and partner cohorts (G0). This spans a period of ~28 years from pregnancy onwards. We also describe the coding of text-based responses from their offspring (G1) collected at ages 27+ and 29+. The creation of this coded data will enable researchers to compare between the Christian denominations and/or other belief groups taken from two generations alongside the rich resource of physical and mental health, behavioural and social data that exists within ALSPAC.

Exploring the Role of Vitamin D and the Gut Microbiome: A Cross-Sectional Study of Individuals with Irritable Bowel Syndrome and Healthy Controls.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and HC (n=62). Plasma concentrations of 25(OH)D were assessed using the Endocrine Society Guidelines definition of vitamin D deficiency (25(OH)D <20 ng/ml) and insufficiency (25(OH)D >20-<30 ng/ml). 16S rRNA microbiome gene sequencing data was available for 39 HC and 62 participants with IBS. Genus-level Bifidobacterium and Lactobacillus and phylum-level Firmicutes and Bacteroidetes relative abundances were extracted from microbiome profiles. Results showed vitamin D deficiency in 40.3% (n=25) vs. 41.4% (n=41), and insufficiency 33.9% (n=21) vs. 34.3% (n=34) in the HCs vs. IBS groups, respectively. The odds of IBS did not differ depending on 25(OH)D status (p=0.75 for deficient, p=0.78 for insufficient), and the average plasma vitamin D concentration did not differ between IBS (mean 24.8 ng/ml) and HCs (mean 25.1 ng/ml; p=0.57). We did not find evidence of an association between plasma 25(OH)D concentration and richness, Shannon index, Simpson index or specific bacterial abundances in either HCs or the IBS group.

Health system capacity to manage diabetic ketoacidosis in nine low-income and lower-middle income countries: A cross-sectional analysis of nationally representative survey data.

Background: There has been increasing awareness about the importance of type 1 diabetes (T1D) globally. Diabetic ketoacidosis (DKA) is a life-threatening complication of T1D in low-income settings. Little is known about health system capacity to manage DKA in low- and lower-middle income countries (LLMICs). As such, we describe health system capacity to diagnose and manage DKA across nine LLMICs using data from Service Provision Assessments. Methods: In this cross-sectional study, we used data from Service Provision Assessment (SPA) surveys, which are part of the Demographic and Health Survey (DHS) Program. We defined an item set to diagnose and manage DKA in higher-level (tertiary or secondary) facilities, and a set to assess and refer patients presenting to lower-level (primary) facilities. We quantified each item's availability by service level in Bangladesh (Survey 1: May 22 2014-Jul 20 2014; Survey 2: Jul 2017-Oct 2017), the Democratic Republic of the Congo (DRC) (Oct 16 2017-Nov 24 2017 in Kinshasha; Aug 08 2018-Apr 20 2018 in rest of country), Haiti (Survey 1: Mar 05 2013-Jul 2013; Survey 2: Dec 16 2017-May 09 2018), Ethiopia (Feb 06 2014-Mar 09 2014), Malawi (Phase 1: Jun 11 2013-Aug 20 2013; Phase 2: Nov 13 2013-Feb 7 2014), Nepal (Phase 1: Apr 20 2015-Apr 25 2015; Phase 2: Jun 04 2015-Nov 05 2015), Senegal (Survey 1: Jan 2014-Oct 2014; Survey 2: Feb 09 2015-Nov 10 2015; Survey 3: Feb 2016-Nov 2016; Survey 4: Mar 13 2017-Dec 15 2017; Survey 5: Apr 15 2018-Dec 31 2018; Survey 6: Apr 15 2019-Feb 28 2020), Tanzania (Oct 20 2014-Feb 21 2015), and Afghanistan (Nov 1 2018-Jan 20 2019). Variation in secondary facilities' capacity and trends over time were also explored. Findings: We examined data from 2028 higher-level and 7534 lower-level facilities. Of these, 1874 higher-level and 6636 lower-level facilities' data were eligible for analysis. Availability of all item sets were low at higher-level facilities, where less than 50% had the minimal set of supplies, less than 20% had the full minimal set, and less than 15% had the ideal set needed to diagnose and manage DKA. Across countries in lower-level facilities, less than 14% had the minimal set of supplies and less than 9% the full set of supplies for diagnosis and transfer of DKA patients. No country had more than 20% of facilities with the minimal set of items needed to assess or manage DKA. Where data were available for more than one survey (Bangladesh, Senegal, and Haiti), changes in availability of the minimal set and ideal set of items did not exceed 15%. Tertiary facilities performed best in Haiti, Ethiopia, Malawi, Nepal, Senegal, Tanzania, and Afghanistan. Secondary facilities that were rural, public, and had fewer staff had lower capacity. Interpretation: Health system capacity to manage DKA was low across these nine LLMICs. Although efforts are underway to strengthen health systems, a specific focus on DKA management is still needed. Funding: Leona M. and Harry B. Helmsley Charitable Trust, and Juvenile Diabetes Research Foundation Ltd.