Sociodemographic and Behavioral Factors Associated With Hypertension and Depression in 4 Rural Communities in Northern Ghana: A Cross-Sectional Study.

OBJECTIVES: The prevalences of hypertension and depression in sub-Saharan Africa are substantial and rising, despite limited data on their sociodemographic and behavioral risk factors and their interactions. We undertook a cross-sectional study in 4 communities in the Upper East Region of Ghana to identify persons with hypertension and depression in the setting of a pilot intervention training local nurses and health volunteers to manage these conditions. METHODS: We quantified hypertension and depression prevalence across key sociodemographic factors (age, sex, occupation, education, religion, ethnicity, and community) and behavioral factors (tobacco use, alcohol use, and physical activity) and tested for association by multivariable logistic regression. RESULTS: Hypertension prevalence was higher in older persons (7.6% among 35- to 50-year-olds vs 16.4% among 51- to 70-year-olds) and among those reporting alcohol use (18.9% vs 8.5% between users and nonusers). In multivariable models, only older age (AOR 2.39 [1.02, 5.85]) and residence in the community of Wuru (AOR 7.60 [1.81, 32.96]) were independently associated with hypertension, and residence in Wuru (AOR 23.58 [7.75-78.25]) or Navio (AOR 7.41 [2.30-24.74]) was the only factor independently associated with depression. CONCLUSIONS: We report a high prevalence of both diseases overall and in select communities, a trend that requires further research to inform targeted chronic disease interventions.

Emotional and Financial Stressors in New York City During the COVID-19 Pandemic: A Consecutive Cross-Sectional Analysis.

Mental and financial hardship during the COVID-19 pandemic in New York City was severe, but how vulnerable groups have been disproportionately impacted is incompletely understood. In partnership with community stakeholders, we administered a web-based survey to a convenience sample of New York City residents (18 + years) from May 2020 to April 2021 to evaluate their financial and emotional stressors. We analyzed outcomes by race, ethnicity, and education level. A total of 1854 adults completed the survey across three consecutive non-overlapping samples. Fifty-five percent identified other than non-Latinx White. Sixty-four percent reported emotional stress; 38%, 32%, and 32% reported symptoms of anxiety, depression, and post-traumatic stress disorder respectively; and 21% reported a large adverse financial impact. The leading unmet needs were mental health and food services (both 19%), and health services (18%). Need for both resources grew over time. Adverse financial impact directly correlated with presence of all four adverse mental health outcomes above. In multivariate analysis, non-White race and lack of college degree were associated with adverse financial impact, whereas LGBT identity and lack of college degree were associated with mental health impact. Throughout the COVID-19 pandemic, participants in this research demonstrated a large and growing mental and financial strain, disproportionately associated with lower education level, non-White race, and LGBT status. Our findings suggest an urgent need to differentially target COVID-19 mental health and resource support in New York City to persons in these vulnerable communities.

Bringing Generalists to Global Health: a Missed Opportunity and Call to Action.

The credo of the generalist physician has always been the promotion of health for all, in every aspect: not just multiple vulnerable organ systems, but multiple social, cultural, and political factors that contribute to poor health and exacerbate health inequity. In recent years, the field of global health has also adopted this same mission: working across both national and clinical specialty borders to improve health for all and end health disparities worldwide. Yet within the Society for General Internal Medicine, and among American generalists, engagement in global health, both within and outside the USA, remains uncommon. We see this gap as an opportunity, because in fact generalists in America already have the skills and experience that global health badly needs. SGIM could promote generalists to global health's vanguard, with three core steps. First, we generalists must continue to integrate health for the vulnerable into our domestic work, generating care models applicable in low-resource settings around the globe. Conversely, we must also engage with and implement international ideas and solutions for universal access to primary care for vulnerable patients in the USA. And lastly, we must build platforms to connect ourselves with colleagues worldwide to exchange these learnings.

Associations between opioid overdose deaths and drugs confiscated by law enforcement and submitted to crime laboratories for analysis, United States, 2014-2019: an observational study.

Background: The overdose epidemic in the United States (US) continues to generate unprecedented levels of mortality. There is urgent need for a national data system capable of yielding high-quality, timely, and actionable information on existing and emerging drugs. Public health researchers have started using law enforcement forensic laboratory data to obtain surveillance information on illicit drugs. This study is the first to use drug reports from the entire US to examine correlations between a changing drug supply and increasing opioid-involved overdose deaths (OOD) on a national scale. Methods: This study is observational and investigates associations between law enforcement drug reports and OOD for the US from 2014 to 2019. OOD data are from the Centers for Disease Control and Prevention's National Vital Statistics System restricted-use multiple cause of death files. The US Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) contains forensic laboratory-tested drug exhibit information for the entire US (NFLIS-Drug). Counts of forensic laboratory reports and OOD were aggregated for each state by month, quarter, and year. A difference-in-differences framework was used to estimate contemporaneous and lagged associations. Findings: Between 2014 and 2019 in the US, 249,522 OOD were reported, with the annual number nearly doubling from 28,723 to 50,179. OOD involving illicitly manufactured fentanyls (IMF) also increased substantially during this period, from 19.4% to 72.9%. In addition, 3,817,438 forensic laboratory reports in the US that were reported to NFLIS-Drug contained an opioid, stimulant, or benzodiazepine. Reports of fentanyl and fentanyl-related compounds (FFRC) had the strongest association with OOD. Each additional FFRC exhibit was associated with a 2.97% (95% CI: 1.7%, 4.1%) increase in OOD per 100,000 persons per quarter. Interpretation: Adding to the emerging consensus, protracted growth in IMF supply was more strongly associated with OOD than all other illicit drugs reported to NFLIS-Drug over the study time period. Findings demonstrate NFLIS-Drug data usefulness for research that require proxy indicators for the illicit drugs supply. A concerted effort between public health and public safety to make NFLIS-Drug more timely could strengthen its utility as a national, public health, drug surveillance system. Funding: Sangeetha Arctic Slope Mission Services, LLC, ASMS Contract No. ASM5-00017.

Understanding research methods, limitations, and applications of drug data collected by the National Forensic Laboratory Information System (NFLIS-Drug).

The National Forensic Laboratory Information System (NFLIS) is a drug surveillance program of the US Drug Enforcement Administration that systematically collects data on drugs that are seized by law enforcement and submitted to and analyzed by the Nation's forensic laboratories (NFLIS-Drug). NFLIS-Drug data are increasingly used in predictive modeling and drug surveillance to examine drug availability patterns. Given the complexity of the data and data collection, there are some common methodological pitfalls that we highlight with the aim of helping researchers avoid these concerns. The analysis done for this Technical Note is based on a review of the scientific literature that includes 428 unique, refereed article citations in 182 distinct journals published between January 1, 2005, and April 30, 2021. Each article was analyzed according to how NFLIS-Drug data were mentioned and whether NFLIS-Drug data were included. A sample of 37 articles was studied in-depth, and data issues were summarized. Using examples from the literature, this Technical Note highlights eight broad concerns that have important implications for the proper applications, interpretations, and limitations of NFLIS-Drug data with suggestions for improving research methods and accurate reporting of forensic drug data. NFLIS-Drug data are timely and provide key information to inform drug use trends across the United States; however, our present analysis shows that NFLIS-Drug data are misunderstood and represented in the literature. In addition to highlighting these issues, DEA has created several resources to assist NFLIS data users and researchers, which are summarized in the discussion.

Linear: a framework to enable existing software to resolve structural variants in long reads with flexible and efficient alignment-free statistical models.

Alignment is the cornerstone of many long-read pipelines and plays an essential role in resolving structural variants (SVs). However, forced alignments of SVs embedded in long reads, inflexibility of integrating novel SVs models and computational inefficiency remain problems. Here, we investigate the feasibility of resolving long-read SVs with alignment-free algorithms. We ask: (1) Is it possible to resolve long-read SVs with alignment-free approaches? and (2) Does it provide an advantage over existing approaches? To this end, we implemented the framework named Linear, which can flexibly integrate alignment-free algorithms such as the generative model for long-read SV detection. Furthermore, Linear addresses the problem of compatibility of alignment-free approaches with existing software. It takes as input long reads and outputs standardized results existing software can directly process. We conducted large-scale assessments in this work and the results show that the sensitivity, and flexibility of Linear outperform alignment-based pipelines. Moreover, the computational efficiency is orders of magnitude faster.

Community perspectives on cardiovascular disease control in rural Ghana: A qualitative study.

BACKGROUND: Cardiovascular disease (CVD) prevalence is high in Ghana-but awareness, prevention, and treatment is sparse, particularly in rural regions. The nurse-led Community-based Health Planning and Services program offers general preventive and primary care in these areas, but overlooks CVD and its risk factors. METHODS: We conducted in-depth interviews with 30 community members (CM) in rural Navrongo, Ghana to understand their knowledge and beliefs regarding the causes and treatment of CVD and the potential role of community nurses in rendering CVD care. We transcribed audio records, coded these data for content, and qualitatively analyzed these codes for key themes. RESULTS: CMs described CVD as an acute, aggressive disease rather than a chronic asymptomatic condition, believing that CVD patients often die suddenly. Yet CMs identified causal risk factors for CVD: not only tobacco smoking and poor diet, but also emotional burdens and stressors, which cause and exacerbate CVD symptoms. Many CMs expressed interest in counseling on these risk factors, particularly diet. However, they felt that nurses could provide comprehensive CVD care only if key barriers (such as medication access and training) are addressed. In the interim, many saw nurses' main CVD care role as referring to the hospital. CONCLUSIONS: CMs would like CVD behavioral education from community nurses at local clinics, but feel the local health system is now too fragile to offer other CVD interventions. CMs believe that a more comprehensive CVD care model would require accessible medication, along with training for nurses to screen for hypertension and other cardiovascular risk factors-in addition to counseling on CVD prevention. Such counseling should build upon existing community beliefs and concerns regarding CVD-including its behavioral and mental health causes-in addition to usual measures to prevent CVD mortality such as diet changes and physical exercise.

Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes.

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements.

Social and demographic correlates of cardiovascular mortality in the Kassena-Nankana districts of Ghana: a verbal post-mortem analysis.

BACKGROUND: The burden of cardiovascular disease (CVD) in Ghana is rising, but details on its epidemiology are scarce. We sought to quantify mortality due to CVD in two districts in rural Ghana using verbal post-mortem (VPM) data. METHODS: We conducted a proportional sub-hazards analysis of 10 232 deaths in the Kassena-Nankana East and West districts from 2005 to 2012, to determine adult mortality attributed to CVD over time. We stratified results by age, gender and socio-economic status (SES), and compared CVD mortality among SES and gender strata over time. A competing risk model estimated the cumulative effect of eliminating CVD from the area. RESULTS: From 2005 to 2012, CVD mortality more than doubled overall, from 0.51 deaths for every 1000 person-years in 2005 to 1.08 per 1000 person-years in 2012. Mortality peaked in 2008 at 1.23 deaths per 1000 person-years. Increases were comparable in men (2.0) and women (2.3), but greater among the poorest residents (3.3) than the richest (1.3), and among persons aged 55-69 years (2.1) than those aged ≥70 years (1.8). By 2012, male and female CVD mortality was highest in middle-SES persons. We project that eliminating CVD would increase the number of individuals reaching age 73 years from 35% to 40%, adding 1.6 years of life expectancy. CONCLUSIONS: The burden of CVD on overall mortality in the Upper East Region is substantial and markedly increasing. CVD mortality has especially increased in lower-income persons and persons in middle age. Further initiatives for the surveillance and control of CVD in these vulnerable populations are needed.

Hypertension screening, prevalence, treatment, and control at a large private hospital in Kampala, Uganda: A retrospective analysis.

Adult hypertension prevalence in Uganda is 27%, but only 8% are aware of their diagnosis, accordingly treatment and control levels are limited. The private sector provides at least half of care nationwide, but little is known about its effectiveness in hypertension control. We analyzed clinical data from 39 235 outpatient visits among 17 777 adult patients from July 2017 to August 2018 at Uganda's largest private hospital. We calculated blood pressure screening rate at every visit, and hypertension prevalence, medication treatment, and control rates among the 5 090 patients with two or more blood pressure checks who received any medications from the hospital's pharmacy. We defined hypertension in this group as 1) an average of two blood pressure measurements at separate consecutive visits, higher than 140 mm Hg systolic or 90 mm Hg diastolic, 2) receipt of any antihypertensive medication, or 3) the use of a hypertension electronic medical record code. We deemed hypertension control as normotensive at the most recent check. 12 821 (72.1%) of patients received at least 1 blood pressure check. Among the 5 090 patients above, 2 121 (41.6%) had hypertension (33.4% age-standardized to a world population standard): 1 915 (37.6%) with elevated blood pressure, and 170 (3.3%) were normotensive but receiving medication. 838 (39.4%) of patients with hypertension received medication at least once. Overall, 18.3% of patients achieved control (27% of treated patients, and 15% of untreated patients). Hypertension is common and incompletely controlled in this Ugandan private-sector population, suggesting several avenues for novel interventions.

Single-cell sequencing unveils distinct immune microenvironments with CCR6-CCL20 crosstalk in human chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP. DESIGN: We performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort. RESULTS: Deep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay. CONCLUSION: Single-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.

Causes of medication non-adherence and the acceptability of support strategies for people with hypertension in Uganda: A qualitative study.

BACKGROUND: Hypertension is the most common non-communicable disease in Uganda and its prevalence is predicted to grow substantially over the next several years. Rates of hypertension control remain suboptimal, however, due in part to poor medication adherence. There is a significant need to better understand the drivers of poor medication adherence for patients with non-communicable diseases and to implement appropriate interventions to improve adherence. OBJECTIVE: The purpose of this study was two-fold. First, this study sought to understand what factors support or undermine patients' efforts to adhere to their hypertensive medications at baseline. Second, this study sought to explore the acceptability and feasibility of adherence interventions to both providers and patients. METHODS: This study was conducted at a large, urban private hospital in Kampala, Uganda. We conducted key informant interviews with both providers and patients. We explored their beliefs about the causes of medication non-adherence while examining the acceptability of support strategies validated in similar contexts, such as: daily text reminders, educational materials on hypertension, monthly group meetings (i.e. "adherence clubs") led by patients or providers, one-on-one appointments with providers, and modified drug dispensing at the hospital pharmacy. STUDY DESIGN AND PARTICIPANTS: Fifteen healthcare providers and forty-two patients were interviewed. All interviews were transcribed, and these transcripts were analyzed using the NVIVO software. We utilized a conventional content analysis approach informed by the Health Belief Model. RESULTS: Of the proposed interventions, participants expressed particularly strong interest in adherence clubs and educational materials. Participants drew connections between these interventions and previously underexplored drivers of non-adherence, which included the lack of symptoms from untreated hypertension, fear of medication side effects, interest in traditional herbal medicine, and the importance of family and community support. CONCLUSIONS: Both providers and patients at the facility recognized medication non-adherence as a major barrier to hypertension control and expressed interest in improving adherence through interventions that addressed context-specific barriers.

Constructing a Nurse-led Cardiovascular Disease Intervention in Rural Ghana: A Qualitative Analysis.

Background: Cardiovascular disease (CVD) is a growing burden in low- and middle-income countries. Ghana seeks to address this problem by task-shifting CVD diagnosis and management to nurses. The Community-Based Health Planning and Services (CHPS) initiative offers maternal and pediatric health care throughout Ghana but faces barriers to providing CVD care. We employed in-depth interviews to identify solutions to constraints in CVD care to develop a nurse-led CVD intervention in two districts of Ghana's Upper East Region. Objective: This study sought to identify non-physician-led interventions for the screening and treatment of cardiovascular disease to incorporate into Ghana's current primary health care structure. Methods: Using a qualitative descriptive design, we conducted 31 semistructured interviews of community health officers (CHOs) and supervising subdistrict officers (SDOs) at CHPS community facilities. Summative content analysis revealed the most common intervention ideas and endorsements by the participants. Findings: Providers endorsed three interventions: increasing community CVD knowledge and engagement, increasing nonphysician prescribing abilities, and ensuring provider access to medical and transportation equipment. Providers suggested community leaders and volunteers should convey CVD knowledge, marshaling established gathering practices to educate communities and formulate action plans. Providers requested lectures paired with experiential learning to improve their prescribing confidence. Providers recommended revising reimbursement and equipment procurement processes for expediting access to necessary supplies. Conclusions: Frontline CHPS primary care providers believe CVD care is feasible. They recommended a three-pronged intervention that combines community outreach, provider training, and logistical support, thereby expanding task-shifting beyond hypertension to include other CVD risk factors. This model could be replicable elsewhere.

Benzodiazepines reported in NFLIS-Drug, 2015 to 2018.

The National Forensic Laboratory Information System (NFLIS) is a program of the U.S. Drug Enforcement Administration, Diversion Control Division. The NFLIS-Drug component collects drug identification results and associated information from drug cases submitted to and analyzed by federal, state, and local forensic laboratories. This paper presents national annual estimates and national and regional yearly trend differences for clonazepam, diazepam, flubromazolam, clonazolam, and etizolam using annual report rates per 100,000 persons aged 15 or older between 2015 and 2018. An estimated 263,538 benzodiazepine reports were identified by state and local laboratories between 2015 and 2018. Methamphetamine, cocaine, and heroin accounted for 32% of the drugs reported in the same item as alprazolam. Depressants and tranquilizers and narcotic analgesics were the drug classes most frequently identified in the same item as etizolam. A timeline of some benzodiazepines' emergence in NFLIS-Drug is shown, as well as state- and county-level data for selected benzodiazepines.

SVIM-asm: structural variant detection from haploid and diploid genome assemblies.

MOTIVATION: With the availability of new sequencing technologies, the generation of haplotype-resolved genome assemblies up to chromosome scale has become feasible. These assemblies capture the complete genetic information of both parental haplotypes, increase structural variant (SV) calling sensitivity and enable direct genotyping and phasing of SVs. Yet, existing SV callers are designed for haploid genome assemblies only, do not support genotyping or detect only a limited set of SV classes. RESULTS: We introduce our method SVIM-asm for the detection and genotyping of six common classes of SVs from haploid and diploid genome assemblies. Compared against the only other existing SV caller for diploid assemblies, DipCall, SVIM-asm detects more SV classes and reached higher F1 scores for the detection of insertions and deletions on two recently published assemblies of the HG002 individual. AVAILABILITY AND IMPLEMENTATION: SVIM-asm has been implemented in Python and can be easily installed via bioconda. Its source code is available at github.com/eldariont/svim-asm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chromosome-scale, haplotype-resolved assembly of human genomes.

Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98-99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.

Predictors of nursing leadership in Uganda: a cross-sectional study.

Evidence regarding the role of nurses-in-leadership and how to engage nurses in policy decisions is minimal in sub-Saharan Africa. The purpose of this study was: (1) to assess the leadership practices of nurses-in-leadership in Uganda (by self-report) and from the perspective of 'followers' (direct-report, peers, co-workers, other); and (2) to determine factors (positively) associated with leadership practices. We surveyed 480 nurses, 120 in leadership roles (Response Rate 57%) and 360 'followers' (Response Rate 60%), who were recruited from five hospitals in Kampala, Uganda. We used the Leadership Practice Inventory (Self and Observer), a project-specific demographic questionnaire and Denison's Organizational Culture Survey (DOCS). Sixty-three per cent of the respondents held a registered nursing certificate; 79% had received formal leadership training; 47% were based in private for-profit (PFP) hospitals, 28% in private not-for-profit (PNFP) and 25% in public hospitals. Among the five leadership practices, nurses-in-leadership used the practice of Model the Way (M = 8.27, SD = 1.30), Challenge the Process (M = 8.12, SD = 1.30) and Encourage the Heart (M = 8.04, SD = 1.51) more frequently (on a 10-point Likert Scale). Inspire a Shared Vision (M = 7.82, SD = 1.57) and Enable Others to Act (M = 7.62, SD = 1.66) practices were used less frequently. The same rank order was true for leadership scores from the perception of followers. However, leadership scores by followers were significantly lower (P < 0.01) than the nurse leader self-reported scores across all sub-scales. Leadership practice scores were higher in public than private hospitals (P < 0.0001). Organizational culture (OC) was associated (P < 0.001) with leadership practices. Although overall leadership practice scores were generally high, the less frequent use of Inspire and Enable practices suggests opportunities for targeted improvement. Moreover, differences between self-reported and leadership scores by followers suggest perception gaps between leaders and their followers. The positive relationship between public hospital settings and self-reported leadership practices among nurses-in-leadership suggests that important nursing leadership practices are possible even in a low-resource clinical setting.

The mole genome reveals regulatory rearrangements associated with adaptive intersexuality.

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.

Protecting the vulnerable during COVID-19: Treating and preventing chronic disease disparities.

The coronavirus disease 2019 (COVID-19) pandemic has exacerbated health disparities across ethnic and socioeconomic groups. Non-communicable diseases (NCDs) - such as hypertension, diabetes, and obstructive lung diseases - are key drivers of this widening gap, because they disproportionately afflict vulnerable populations. Vulnerable populations with non-communicable diseases, in turn, are disproportionately affected by COVID-19 itself - but also at increased risk of poor outcomes from those underlying conditions. Proven strategies for NCD control must be adapted to help vulnerable patients react to these dual threats. We detail six key policy interventions - task shifting, workforce protection, telehealth and mobile services, insurance restructuring and increased funding for NCDs, prescription policies for NCDs and community partnerships - to bridge this care gap. Long-term integration of these care models post-COVID-19 may prevent care shocks during future pandemics, bolstering emerging universal primary care models.

Two-drug fixed-dose combinations of blood pressure-lowering drugs as WHO essential medicines: An overview of efficacy, safety, and cost.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all-cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Most patients (>60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed-dose combinations (FDCs) of BP-lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP-lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP-lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies.