Search

Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder characterized by a collection of clinical features including mild to severe intellectual disability, hypertonia, marfanoid habitus, facial asymmetry, osteoporosis, developmental delay and seizures. Whole genome sequencing (WGS) identified a mutation in the spermine synthase (SMS) gene (c.746 A>G, p.Tyr249Cys) in a male with kyphosis, seizures, and osteoporosis. His phenotype is unique in that he does not have intellectual disability (ID) but does have a mild learning disability. This case demonstrates a milder presentation of SRS and expands the phenotype beyond the reported literature.

Rice (Oryza sativa L.) is an important food crop relied upon by billions of people worldwide. However, with increasing pressure from climate change and rapid population growth, cultivation is very water-intensive. Therefore, it is critical to produce rice that is high-yielding and genetically more water-use efficient. Here, using the stabilized fast-neutron mutagenized population of Jao Hom Nin (JHN) - a popular purple rice cultivar - we microscopically examined hundreds of flag leaves to identify four stomatal model mutants with either high density (HD) or low density (LD) stomata, and small-sized (SS) or large-sized (LS) stomata. With similar genetic background and uniformity, the stomatal model mutants were used to understand the role of stomatal variants on physiological responses to abiotic stress. Our results show that SS and HD respond better to increasing CO2 concentration and HD has higher stomatal conductance (gs) compared to the other stomatal model mutants, although the effects on gas exchange or overall plant performance were small under greenhouse conditions. In addition, the results of our drought experiments suggest that LD and SS can better adapt to restricted water conditions, and LD showed higher water use efficiency (WUE) and biomass/plant than other stomatal model mutants under long-term restricted water treatment. Finally, our study suggests that reducing stomata density and size may play a promising role for further work on developing a climate-ready rice variety to adapt to drought and heat stress. We propose that low stomata density and small size have high potential as genetic donors for improving WUE in climate-ready rice.

Abstract Background Civic engagement, including voting, volunteering, and participating in civic organizations, is associated with better psychological, physical and behavioral health and well-being. In addition, civic engagement is increasingly viewed (e.g., in Robert Wood Johnson Foundation’s Culture of Health action framework) as a potentially important driver for raising awareness of and addressing unhealthy conditions in communities. As such, it is important to understand the factors that may promote civic engagement, with a particular focus on the less-understood, health civic engagement, or civic engagement in health-related and health-specific activities. Using data from a nationally representative sample of adults in the United States (U.S.), we examined whether the extent to which individuals feel they belong in their community (i.e., perceived sense of community) and the value they placed on investing in community health were associated with individuals’ health civic engagement. Methods Using data collected on 7187 nationally representative respondents from the 2018 National Survey of Health Attitudes, we examined associations between sense of community, valued investment in community health, and perceived barriers to taking action to invest in community health, with health civic engagement. We constructed continuous scales for each of these constructs and employed multiple linear regressions adjusting for multiple covariates including U.S. region and city size of residence, educational attainment, family income, race/ethnicity, household size, employment status, and years living in the community. Results Participants who endorsed (i.e., responded with mostly or completely) all 16 sense of community scale items endorsed an average of 22.8% (95%CI: 19.8–25.7%) more of the health civic engagement scale items compared with respondents who did not endorse any of the sense of community items. Those who endorsed (responded that it was an important or top priority) all items capturing valued investment in community health endorsed 14.0% (95%CI: 11.2–16.8%) more of the health civic engagement items than those who did not endorse any valued investment in community health items. Conclusions Health civic engagement, including voting and volunteering to ultimately guide government decisions about health issues, may help improve conditions that influence health and well-being for all. Focusing on individuals’ sense of community and highlighting investments in community health may concurrently be associated with increased health civic engagement and improved community and population health.

Guard cells allow land plants to survive under restricted or fluctuating water availability. They control the exchange of gases between the external environment and the interior of the plant by regulating the aperture of stomatal pores in response to environmental stimuli such as light intensity, and are important regulators of plant productivity. Their turgor driven movements are under the control of a signalling network that is not yet fully characterised. A reporter gene fusion confirmed that the Arabidopsis APK1b protein kinase gene is predominantly expressed in guard cells. Infrared gas analysis and stomatal aperture measurements indicated that plants lacking APK1b are impaired in their ability to open their stomata on exposure to light, but retain the ability to adjust their stomatal apertures in response to darkness, abscisic acid or lack of carbon dioxide. Stomatal opening was not specifically impaired in response to either red or blue light as both of these stimuli caused some increase in stomatal conductance. Consistent with the reduction in maximum stomatal conductance, the relative water content of plants lacking APK1b was significantly increased under both well-watered and drought conditions. We conclude that APK1b is required for full stomatal opening in the light but is not required for stomatal closure.

Abstract Background Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes. Careful interpretation remains warranted because eQTL can affect the expression of multiple genes within the same locus. Methods We used a combination of genomic features that include variant annotation, activity-by-contact maps, MR, and colocalization with molQTL to prioritize causal genes across 4,611 disease GWAS and meta-analyses from biobank studies, namely FinnGen, Estonian Biobank and UK Biobank. Results Genes identified using this approach are enriched for gold standard causal genes and capture known biological links between disease genetics and biology. In addition, we find that eQTL colocalizing with GWAS are statistically enriched for corresponding disease-relevant tissues. We show that predicted directionality from MR is generally consistent with matched drug mechanism of actions (> 85% for approved drugs). Compared to the nearest gene mapping method, genes supported by multi-omics evidences displayed higher enrichment in approved therapeutic targets (risk ratio 1.75 vs. 2.58 for genes with the highest level of support). Finally, using this approach, we detected anassociation between the IL6 receptor signal transduction gene IL6ST and polymyalgia rheumatica, an indication for which sarilumab, a monoclonal antibody against IL-6, has been recently approved. Conclusions Combining variant annotation, activity-by-contact maps, and molQTL increases performance to identify causal genes, while informing on directionality which can be translated to successful target identification and drug development.

The Wallace Foundation is funding a multiyear demonstration project to determine whether voluntary, district summer learning programs can stem summer learning loss for low-income students. Six districts--Boston, Cincinnati, Dallas, Duval County (Florida), Pittsburgh, and Rochester, New York--were selected for the demonstration project and committed themselves to offering such programs to large numbers of at-risk elementary students. These programs are all voluntary; offer reading, mathematics, and enrichment activities such as arts, sports, and science exploration; operate for a full day; provide transportation to students; are free of charge; and share a goal of maintaining or improving student achievement. They served students rising from third into fourth grade, and most served other grade levels as well. To gather information for evaluations of the six districts for the years 2011, 2012, and 2013, the authors interviewed district leaders and summer site leaders and teachers; surveyed teachers, parents, and students; observed program training, instruction, and logistics; engaged professors of elementary education reading and mathematics to review the curricula; gathered program cost data; and analyzed district data on attendance. Although the demonstration project is not complete, key lessons can be drawn in six broad areas: (1) planning; (2) curriculum; (3) teacher selection and training; (4) enrichment activities; (5) academic time on task, and (6) Program cost and funding. Lessons for school district administrators and state policymakers are discussed.

Drawing on a statewide study of Florida middle-school reading coaches, this article examines what constitutes, contributes to, and is associated with high-quality coaches and coaching. Authors find that coaches generally held many of the qualifications recommended by state and national experts and principals and teachers rated their coaches highly on many indicators of quality. However, several common concerns about recruiting, retaining, and supporting high-quality coaches emerged. Estimates from models indicate that a few indicators of coach experience, knowledge, and skills had significant associations with perceived improvements in teaching and higher student achievement, although the magnitude of the latter relationship was quite small. Findings suggest that although possessing strong reading knowledge and instructional expertise may be important for coaching, it may not be sufficient. (Contains 1 figure, 5 tables and 11 footnotes.)

This article examines the convergence of two popular school improvement policies: instructional coaching and data-driven decision making (DDDM). Drawing on a mixed methods study of a statewide reading coach program in Florida middle schools, the article examines how coaches support DDDM and how this support relates to student and teacher outcomes. Authors find that although the majority of coaches spent time helping teachers analyze student data to guide instruction, data support was one among many coach activities. Estimates from models indicate that data analysis support, nevertheless, has a significant association with both perceived improvements in teaching and higher student achievement. (Contains 4 tables, 1 figure and 12 notes.)

Many policymakers suggest that school-based reading coaches can improve teachers' practice, which consequently will improve students' literacy skills. Although reading coaches are increasingly prevalent in schools nationwide, empirical evidence for their effects on student achievement is scarce. This article helps to address this gap by conducting an evaluation of a statewide reading coach program in Florida middle schools. Using achievement data from nearly 1,000 Florida middle schools from the 1997-1998 through 2005-2006 school years, we find that receiving a state-funded coach was associated with statistically significant improvements in average annual reading achievement gains for two of the four cohorts of schools analyzed. We examine implications for state and district policy and future research. (Contains 4 notes, 3 tables, and 1 figure.)

Abstract Background Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA. Methods This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized. Results Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n = 6/13) of patients in SAR200 + 26W, 43% (n = 3/7) in SAR150 + 26W, 30% (n = 3/10) in PBO + 52W, and 0 (n = 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (n = 6/10) in PBO + 52W and 17% (n = 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n = 6/13, SAR200 + 26W), 43% (n = 3/7, SAR150 + 26W), 60% (n = 6/10, PBO + 52W), and 33% (n = 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80–100%) experienced treatment-emergent adverse events, with similar incidences reported across groups. Conclusions Owing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings. Trial registration ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.

Human parechovirus (HPeV) belongs to the Picornaviridae family of RNA viruses. HPeV infections can be asymptomatic, lead to mild respiratory and/or gastrointestinal symptoms, or less frequently cause severe diseases such as sepsis, meningitis, encephalitis, and myocarditis. Severe neurological HPeV infections occur most commonly in infants and neonates. There are currently 16 recognized types of HPeV. HPeV type 3 (HPeV3) has been the predominant type associated with severe central nervous system disease in neonates and newborns since its discovery in 1999. Although HPeV-related infections have been reported in adults, symptomatic HPeV3 infections in adolescents and adults are uncommon. A case of severe HPeV3 myocarditis and encephalitis in an adolescent is described.

The Robert Wood Johnson Foundation (RWJF) recently made a commitment to advancing a national culture of health (COH)-an action framework developed by RWJF that focuses on well-being and equity with the goal of empowering and supporting people to lead healthier lives where they live, learn, work, and play, now and in generations to come. Nurses are well positioned to provide care that is consistent with, and contributes to, a COH in their communities. RWJF contracted with the American Academy of Nursing (the Academy) with a subcontract to the RAND Corporation to explore the ways that innovative nurse-designed models of care are currently advancing a COH. This article presents findings from case studies of three nurse-designed care models that have been recognized as innovative by the Academy's Edge Runner program, which identifies nurses who have designed innovations to remedy challenges in the delivery of health care or address an unmet health need of a population, and who can demonstrate positive clinical and financial outcomes. Findings indicate that nurse-designed models of care focus extensively on activities in the four different "action areas" set forth in RWJF's COH framework: making health a shared value; fostering cross-section collaboration to improve well-being; creating healthier, more equitable communities; and strengthening integration of health services and systems. Strong leadership and broad community support were key to the success of each of these models. A persistent challenge was identifying a sustainable funding mechanism for community-level efforts aimed at addressing social determinants of health-most of these efforts are currently grant-funded.

The U.S. Department of Defense has highlighted the importance of preparing health care leaders to succeed in joint, performance-based environments. The current wartime environment, rising health care costs, and an increased focus on joint operations have led to recommendations for Military Health System (MHS) transformation. Part of that transformation will involve improving the identification and development of potential MHS leaders. An examination of how candidates are identified for leadership positions, the training and education opportunities offered to them, and the competencies they are expected to achieve revealed both a range of approaches and several commonalities in the military, civilian, and government sectors. A conceptual framework guided a series of interviews with senior health care executives from a wide range of organizations and military health care leaders from the Army, Navy, and Air Force, as well as a case study of the leader development approaches used by the Veterans Health Administration. Several themes emerged in terms of how leaders are developed in each sector, including the importance of mentoring, career counseling, 360-degree feedback, self-development, and formal education and training programs. Lessons learned in the civilian and government sectors hold importance for transforming the way in which MHS identifies and develops health care officers with high leadership potential for senior executive positions.