The complexity of transferring genetic information.

The Central Dogma has been a useful conceptualization of the transfer of genetic information, and our understanding of the detailed mechanisms involved in that transfer continues to evolve. Here, we speak to several scientists about their research, how it influences our understanding of information transfer, and questions for the future.

Who Gets Sick From COVID-19? Sociodemographic Correlates of Severe Adult Health Outcomes During Alpha- and Delta-Variant Predominant Periods: September 2020-November 2021.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

Effectiveness of Community-Engaged Research Strategies in Increasing COVID-19 Vaccinations in Targeted Communities: The Community Engagement Alliance (CEAL) Regional Teams.

Objectives. To explore a key outcome of interest for the Community Engagement Alliance (CEAL) Regional Teams by examining COVID-19 vaccinations over time in US counties where CEAL teams operated and comparing them to demographically similar counties in the same state. Methods. Our evaluation used a nonequivalent control group design. Each county where a CEAL team operated was matched to a unique non-CEAL county in the same state. Components of the Centers for Disease Control and Prevention's Social Vulnerability Index were used as the matching criteria. COVID-19 vaccinations (county-level percentage of residents aged 18 years or older who are fully vaccinated) for CEAL and matched counties were analyzed over time. Results. The mean percentage of vaccinated adults was significantly higher in CEAL counties than in matched non-CEAL counties. Sensitivity analyses confirmed conclusions did not change depending on the CEAL cohort or closeness of matches. Conclusions. Our findings support CEAL team efforts to increase COVID-19 vaccinations in target communities and employ community-engaged research more broadly within public health contexts. (Am J Public Health. 2024;114(S1):S124-S127. https://doi.org/10.2105/AJPH.2023.307517).

Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study.

INTRODUCTION: Rwanda's Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative "micro-elimination" strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care. METHODS: This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients' clinical programs and hepatitis B and C, and reported cascade of care for the two diseases. RESULTS: Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients < 40 years (2.4%). Increased age was significantly associated with anti-HCV (12.0% among patients ≥ 70 years). Of the 148 individuals who screened positive for HbsAg, 123 had viral load results returned, 101 had detectable viral loads (median viral load: 451 UI/mL), and 12 were linked to care. Of the 507 individuals who screened positive for anti-HCV, 468 had their viral load results returned (median viral load: 1,130,000 UI/mL), 304 had detectable viral loads, and 230 were linked to care. CONCLUSION: Anti-HCV prevalence among Rwandan patients with NCD was high, likely due to their older age. NCD-HCV co-infected patients had high HCV viral loads and may be at risk of poor outcomes from hepatitis C. Hepatitis C micro-elimination campaigns among NCD patients are a feasible and acceptable strategy to enhance case detection in this high-prevalence population with elevated viral loads and may support linkage to care for hepatitis C among elderly populations.

2020 design and methods of the Population Assessment of Tobacco and Health (PATH) study during the COVID-19 pandemic.

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal study of the US population on tobacco use and its effects on health, collecting data annually since 2013. The COVID-19 pandemic interrupted in-person survey data collections around the world. In the USA, this included a PATH Study data collection focused on youth (13-17) and young adults (18-19) as well as other US surveys on tobacco use. Given that it was necessary to pause data collection and considering that tobacco-use behaviours could be expected to change along with pandemic-related changes in the social environment, the original design for the 2020 PATH Study data collection for youth and young adults was modified. Also, the PATH Study Adult Telephone Survey was developed to address the need for adult tobacco use monitoring in this unprecedented time. This article describes the modifications made to the 2020 PATH Study design and protocol to provide nationally representative data for youth and adults after the onset of the COVID-19 pandemic as well as the implications of these modifications for researchers.

Cellular Senescence in Human Skin Aging: Leveraging Senotherapeutics.

BACKGROUND: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health. SUMMARY: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures. KEY MESSAGES: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging.

Twelve tips for designing and implementing an academic coaching program.

Coaching has become increasingly popular as a mechanism to support learning across the health professions education (HPE) continuum. While there is a growing body of literature in this area, there is minimal guidance related to the design and implementation of academic coaching in health professional courses. This paper seeks to contribute to this literature by presenting guidance for academic developers who are considering introducing academic coaching into a health professional course. The 12 tips are based on the authors' collective experiences of designing and implementing academic coaching in university medical courses in Australia and the UK. Although focused on medical education, this paper is intended to have applicability across the health professions, and potentially across university and postgraduate training contexts. Together, the tips offer a strategic and operational framework to guide the design and implementation of academic coaching initiatives in health professions education.

Embracing Spectrum: Celebrating LGBTQIA+ Journeys in Aesthetic Medicine: A Kaleidoscope of Identity.

PURPOSE: This synaptic systemised review critically examines the provision of aesthetic medical care to LGBTQIA+ (lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and more) individuals, assessing both the clinical practices and the educational frameworks that guide interactions with LGBTQIA+ patients in aesthetic settings. METHODS: Following PRISMA-S guidelines, a comprehensive review was conducted, initially identifying 159 potentially relevant articles. Upon stringent full-text review, 33 studies met the inclusion criteria and were subject to an in-depth thematic analysis. The scope encompassed qualitative studies, quantitative analyses, and a cross section of interdisciplinary research, predominantly from Western settings. RESULTS: The analysis distilled four principal themes: the imperative of identity affirmation in aesthetic interventions, substantial barriers to inclusive and empathetic care, the critical need for patient empowerment, and the existing deficiencies within medical education regarding LGBTQIA+ care. These themes highlight a complex interplay between the clinical aspirations of LGBTQIA+ individuals and the current capacity of aesthetic medicine to cater to this diversity. CONCLUSIONS: There is a pressing need for a paradigmatic shift towards more inclusive, competent, and sensitive aesthetic medical care for LGBTQIA+ patients. It underscores the necessity of reform in medical education and advocates for policy changes that promote a more equitable healthcare environment. This research serves as a call to action, emphasizing the ethical imperative to integrate comprehensive LGBTQIA+ care competencies into aesthetic medicine curricula and practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Generational Exploration on Aesthetic Medicine Products: Influence of Social Media, Reviews, and Brand Identity-GEMS Bond Survey.

INTRODUCTION: The study investigates the impact of social media reviews and brand identity on consumer preferences in the non-surgical aesthetics products across different generations. It highlights the evolving landscape of aesthetic medicine and surgery, driven by technological advancements and a cultural shift towards individual well-being. The research aims to explore the interplay between generational preferences, the influence of social media, and the role of brand identity in shaping consumer decisions. METHODS: A cross-sectional study design was employed, with a sample size of > 5000 participants stratified across various generational cohorts. The study utilized an online questionnaire to capture both quantitative and qualitative insights into consumer behaviour, with statistical analysis performed to identify patterns and relationships. RESULTS: Analysis of 5850 responses revealed distinct generational preferences and behaviours. Social media engagement varied significantly across generations, with younger cohorts placing a higher emphasis on online reviews. The study also found that brand identity's influence is diminishing in decision-making processes, with consumers increasingly relying on peer reviews and social media content. CONCLUSION: The findings highlight a pivotal shift in the non-surgical aesthetics consumer market, emphasizing the growing importance of social media and peer reviews over traditional brand identities. Importantly, the study underscores the critical need for integrating patient safety and evidence-based practice within marketing strategies. As consumer preferences evolve towards valuing transparency and authenticity, non-surgical aesthetics providers must prioritize these elements, ensuring that their services are not only appealing but also grounded in safety and scientific validity. LEVEL OF EVIDENCE IV: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

BACKGROUND: Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. OBJECTIVES: The aim was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. METHODS: A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses are based on the number of cases with data available. RESULTS: 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Stroke-like features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (p < .001). The three most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intra-arterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (p > .05). CONCLUSIONS: Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

Multidecadal mangrove forest change in Macajalar Bay, Northern Mindanao, Philippines (1950-2020) using remote sensing and geographic information systems.

The mangrove forest in Macajalar Bay is regarded as an important coastal ecosystem since it provides numerous ecosystem services. Despite their importance, the clearing of mangroves has been rampant and has reached critical rates. Addressing this problem and further advancing its conservation require accurate mangrove mapping. However, current spatial information related to mangroves is sparse and insufficient to understand the historical change dynamics. In this study, the synergy of 1950 vegetation maps and Landsat images was explored to provide multidecadal monitoring of mangrove forest change dynamics in Macajalar Bay, Philippines. Vegetation maps containing the 1950 mangrove extent and Landsat images were used as input data to monitor the rates of loss over 70 years. In 2020, the mangrove forest cover was estimated to be 201.73 ha, equivalent to only 61.99% of the 325.43 ha that was estimated in 1950. Between 1950 and 2020, net mangrove loss in Macajalar Bay totaled 324.29 ha. The highest clearing rates occurred between 1950 and 1990 when it recorded a total of 258.51 ha, averaging 6.46 ha/year. The original mangrove forest that existed in 1950 only represents 8.56% of the 2020 extent, suggesting that much of the old-growth mangrove had been cleared before 2000 and the existing mangrove forest is mainly composed of secondary mangrove forest stands. Across Macajalar Bay, intensified clearing that happened between 1950 and 1990 has been driven by large-scale aquaculture developments. Mangrove gains on the other hand were evident and have increased the total extent by 79.84 ha since 2000 as a result of several afforestation programs. However, approximately half of these gains that were observed since 2010 exhibited low canopy cover. As of writing, approximately 85% of the 2020 mangrove forest stands fall outside the 1950 original mangrove extent. Examining the viability of the original mangrove forest for mangrove reforestation together with promoting site-species matching, and biophysical assessment are necessary undertakings to advance current mangrove conservation initiatives in Macajalar Bay.

Update to the design and methods of the PATH Study, Wave 4 (2016-2017).

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative study of the US population on tobacco use and its effects on health, with four waves of data collection between 2013 and 2017. Prior work described the methods of the first three waves. In this paper, we describe the methods of Wave 4, during which a replenishment sample was added to the ongoing cohort. We describe the design and estimation methods of the continuing Wave 1 cohort (with four waves of data) and the Wave 4 cohort (the new cohort created at Wave 4). We provide survey quality metrics, including response rates for both cohorts and a panel conditioning analysis, and guidance on understanding the target populations for both cohorts.

The Efficacy and Duration of Onabotulinum Toxin A in Improving Upper Facial Expression Lines With 64-Unit Dose Optimization: A Systematic Review and Meta-Analysis With Trial Sequential Analysis of the Randomized Controlled Trials.

BACKGROUND: Onabotulinumtoxin A (Onabot A) was the first treatment to be approved for aesthetic indications, namely glabellar lines (GLs), crow's feet lines (CFLs), and forehead lines (FHLs), with a cumulative dose of 64 U. OBJECTIVES: The aim of this study was to conduct a meta-analysis to combine the available data for approved doses for GLs, CFLs, and FHLs to explore the effect and duration of simultaneous treatment with Onabot A. METHODS: PubMed/MEDLINE, Embase, and other national clinical trial registries were searched for randomized controlled trials from January 2010 to July 2022. The meta-analysis, trial sequential analysis, and investigator-assessed time to return to nonresponder status in GLs, CFLs, and FHLs following Onabot A were plotted to elicit a cumulative dose-adjusted response curve based on Kaplan-Meier analysis with a log-rank test. RESULTS: Fourteen randomized controlled trials were eligible for quantitative analysis. A total of 8369 subjects were recruited across the trials. The meta-analysis results show that Onabot A is very effective in reducing moderate to severe GLs, CFLs, and FHLs. The cumulative Z-curve for GLs, CFLs, and FHLs also exceeds the required information size (RIS). Kaplan-Meier analysis with a log-rank test demonstrated that simultaneous treatment of GLs, CFLs, and FHLs requires 182 days (95% CI = 179, 215 days) (P < 0.00002) to return to nonresponder status. CONCLUSIONS: Treatment of the upper facial expression lines with Onabot A is effective, and the approved cumulative dose of 64 U gives longer-lasting effects.

Integrative Assessment for Optimizing Aesthetic Outcomes When Treating Glabellar Lines With Botulinum Toxin Type A: An Appreciation of the Role of the Frontalis.

Despite the perception that treatment of glabellar lines with botulinum toxin A is straightforward, the reality is that the glabellar region contains a number of interrelated muscles. To avoid adverse outcomes, practitioners need to appreciate how treatment of 1 facial muscle group influences the relative dominance of others. In particular, practitioners need to understand the independent role of the frontalis in eyebrow outcomes and the potential for negative outcomes if the lower frontalis is unintentionally weakened by botulinum toxin A treatment. In addition, practitioners must recognize how inter-individual variation in the depth, shape, and muscle fiber orientation among the upper facial muscles can affect outcomes. For optimal results, treatment of the glabellar complex requires a systematic and individualized approach based on anatomical principles of opposing muscle actions rather than a one-size-fits-all approach. This review provides the anatomical justification for the importance of an integrated assessment of the upper facial muscles and eyebrow position prior to glabellar treatment. In addition, a systematic and broad evaluation system is provided that can be employed by practitioners to more comprehensively assess the glabellar region in order to optimize outcomes and avoid negatively impacting resting brow position and dynamic brow movement.

SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial.

BACKGROUND: Additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the coronavirus disease 2019 (COVID-19) pandemic. We describe safety and durability of immune responses following 2 primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting full-length spike antigen. METHODS: Three dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. RESULTS: INO-4800 appeared well tolerated with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine-producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0-mg dose group. CONCLUSIONS: INO-4800 was well tolerated in a 2-dose primary series and homologous booster in all adults, including elderly participants. These results support further development of INO-4800 for use as primary vaccine and booster. CLINICAL TRIALS REGISTRATION: NCT04336410.

Association of Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seroprevalence and State-Issued Nonpharmaceutical Interventions: United States, 1 August 2020 to 30 March 2021.

BACKGROUND: We assess if state-issued nonpharmaceutical interventions (NPIs) are associated with reduced rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as measured through anti-nucleocapsid (anti-N) seroprevalence, a proxy for cumulative prior infection that distinguishes seropositivity from vaccination. METHODS: Monthly anti-N seroprevalence during 1 August 2020 to 30 March 2021 was estimated using a nationwide blood donor serosurvey. Using multivariable logistic regression models, we measured the association of seropositivity and state-issued, county-specific NPIs for mask mandates, gathering bans, and bar closures. RESULTS: Compared with individuals living in a county with all three NPIs in place, the odds of having anti-N antibodies were 2.2 (95% confidence interval [CI]: 2.0-2.3) times higher for people living in a county that did not have any of the 3 NPIs, 1.6 (95% CI: 1.5-1.7) times higher for people living in a county that only had a mask mandate and gathering ban policy, and 1.4 (95% CI: 1.3-1.5) times higher for people living in a county that had only a mask mandate. CONCLUSIONS: Consistent with studies assessing NPIs relative to COVID-19 incidence and mortality, the presence of NPIs were associated with lower SARS-CoV-2 seroprevalence indicating lower rates of cumulative infections. Multiple NPIs are likely more effective than single NPIs.

Social Vulnerability and Rurality Associated With Higher Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Induced Seroprevalence: A Nationwide Blood Donor Study-United States, July 2020-June 2021.

BACKGROUND: Most studies on health disparities during the coronavirus disease 2019 (COVID-19) pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence in the United States and its associations with race/ethnicity, rurality, and social vulnerability over time. METHODS: This repeated cross-sectional study used data from blood donations in 50 states and Washington, DC, from July 2020 through June 2021. Donor zip codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its 4 themes were quantified using multivariate regression models. RESULTS: Weighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or more socially vulnerable counties, after adjusting for demographic and geographic covariates. CONCLUSIONS: The findings demonstrated increasing SARS-CoV-2 seroprevalence in the United States across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.

Population-Weighted Seroprevalence From Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Vaccination, and Hybrid Immunity Among US Blood Donations From January to December 2021.

BACKGROUND: Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined ("hybrid immunity"), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the US population who have been infected, vaccinated, or have hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. METHODS: In this serial cross-sectional study, nationwide blood donor specimens collected during January-December 2021 were tested for anti-spike and anti-nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population and were compared temporally and by demographic factors. RESULTS: Overall, 1 123 855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity changed as follows: seropositivity due to vaccination without previous infection, increase from 3.5% (95% confidence interval, 3.4%-3.7%) to 64.0%, (63.5%-64.5%); seropositivity due to previous infection without vaccination, decrease from 15.6% (15.2%-16.0%) to 11.7% (11.4%-12.0%); and seropositivity due to hybrid immunity, increase from 0.7% (0.6%-0.7%) to 18.9% (18.5%-19.3%). Combined seroprevalence from infection, vaccination, or both increased from 19.8% (19.3%-20.2%) to 94.5% (93.5%-94.0%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by sex. CONCLUSIONS: Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.

Revisiting the window of opportunity for cotranscriptional splicing in budding yeast.

We reported previously that, in budding yeast, transcription rate affects both the efficiency and fidelity of pre-mRNA splicing, especially of ribosomal protein transcripts. Here, we report that the majority of ribosomal protein transcripts with non-consensus 5' splice sites are spliced less efficiently when transcription is faster, and more efficiently with slower transcription. These results support the "window of opportunity" model, and we suggest a possible mechanism to explain these findings.

A cost analysis of the diagnosis and treatment of malaria at public health facilities and communities in three districts in Rwanda.

BACKGROUND: Malaria is a potentially fatal disease spread by the bites of Plasmodium-infected Anopheles mosquitoes. Despite long-term efforts to control malaria in Rwanda, malaria incidence increased from 48 to 403 cases/1000 individuals between 2012 and 2016. The diagnosis and treatment of malaria occurs at multiple levels, but the costs of these activities are not well understood. This research was conducted to estimate the direct medical costs incurred by the Ministry of Health in diagnosing and treating malaria in three districts of Rwanda in 2018. METHODS: A cross-sectional and retrospective costing analysis was conducted in three districts that represented low (5-200 cases per 1000 individuals), moderate (> 200-400 cases per 1000 individuals), and high (> 400 cases per 1000 individuals) endemicity regions. Data on malaria cases managed at three healthcare levels (community, health centre, district hospital) was obtained from national databases. The direct medical costs of cases per malaria severity ('simple malaria', 'simple malaria with minor digestive symptoms', and 'severe malaria') were calculated based on the minimum package of health services provided. Total costs for each of the three districts were also calculated. RESULTS: A total of 298,381 malaria cases were recorded in Burera, Kirehe, and Southern Kayonza districts in 2018. The average unit cost per case ranged from USD 1.36 (for simple malaria at the community level) to USD 92.80 (for severe malaria with cerebral complications at district hospitals). Simple malaria cases managed at health centres and district hospitals were more than two-fold (USD 2.99-USD 3.00) and more than eight-fold (USD 12.10-USD 12.12) higher, respectively, than those managed in the community (USD 1.36). Overall, the Ministry of Health incurred USD 645,647.68 in direct medical costs related to malaria management across the three districts in 2018. Changes in disease rates from different endemicity regions and costs of anti-malarial oral medications significantly impacted the study results. CONCLUSION: In Rwanda, severe malaria results in much higher expenses compared to other malaria types. Prompt diagnosis and appropriate treatment are crucial to prevent the progression of simple malaria to severe malaria, to reduce Ministry of Health malaria expenditures, and to reduce community transmission.