Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin.

Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.

Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

Trends in Laboratory-Confirmed SARS-CoV-2 Reinfections and Associated Hospitalizations and Deaths Among Adults Aged ≥18 Years - 18 U.S. Jurisdictions, September 2021-December 2022.

Although reinfections with SARS-CoV-2 have occurred in the United States with increasing frequency, U.S. epidemiologic trends in reinfections and associated severe outcomes have not been characterized. Weekly counts of SARS-CoV-2 reinfections, total infections, and associated hospitalizations and deaths reported by 18 U.S. jurisdictions during September 5, 2021-December 31, 2022, were analyzed overall, by age group, and by five periods of SARS-CoV-2 variant predominance (Delta and Omicron [BA.1, BA.2, BA.4/BA.5, and BQ.1/BQ.1.1]). Among reported reinfections, weekly trends in the median intervals between infections and frequencies of predominant variants during previous infections were calculated. As a percentage of all infections, reinfections increased substantially from the Delta (2.7%) to the Omicron BQ.1/BQ.1.1 (28.8%) periods; during the same periods, increases in the percentages of reinfections among COVID-19-associated hospitalizations (from 1.9% [Delta] to 17.0% [Omicron BQ.1/BQ.1.1]) and deaths (from 1.2% [Delta] to 12.3% [Omicron BQ.1/BQ.1.1]) were also substantial. Percentages of all COVID-19 cases, hospitalizations, and deaths that were reinfections were consistently higher across variant periods among adults aged 18-49 years compared with those among adults aged ≥50 years. The median interval between infections ranged from 269 to 411 days by week, with a steep decline at the start of the BA.4/BA.5 period, when >50% of reinfections occurred among persons previously infected during the Alpha variant period or later. To prevent severe COVID-19 outcomes, including those following reinfection, CDC recommends staying up to date with COVID-19 vaccination and receiving timely antiviral treatments, when eligible.

Investigating the Genetic Diversity of H5 Avian Influenza Viruses in the United Kingdom from 2020-2022.

Since 2020, the United Kingdom and Europe have experienced annual epizootics of high-pathogenicity avian influenza virus (HPAIV). The first epizootic, during the autumn/winter of 2020-2021, involved six H5Nx subtypes, although H5N8 HPAIV dominated in the United Kingdom. While genetic assessments of the H5N8 HPAIVs within the United Kingdom demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes.  Following a small number of detections of H5N1 in wild birds over the summer of 2021, the autumn/winter of 2021-2022 saw another European H5 HPAIV epizootic that dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggest that the H5N1 viruses circulating in Europe during late 2020 continued to circulate in wild birds throughout 2021, with minimal adaptation, but then went on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the United Kingdom over two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk, and whether incidents of lateral spread can be defined over independent incursions of infections from wild birds. This provides key supporting data for mitigation activities. IMPORTANCE High-pathogenicity avian influenza virus (HPAIV) outbreaks devastate avian species across all sectors, having both economic and ecological impacts through mortalities in poultry and wild birds, respectively. These viruses can also represent a significant zoonotic risk. Since 2020, the United Kingdom has experienced two successive outbreaks of H5 HPAIV. While H5N8 HPAIV was predominant during the 2020-2021 outbreak, other H5 subtypes were also detected. The following year, there was a shift in the subtype dominance to H5N1 HPAIV, but multiple H5N1 genotypes were detected. Through the thorough utilization of whole-genome sequencing, it was possible to track and characterize the genetic evolution of these H5 HPAIVs in United Kingdom poultry and wild birds. This enabled us to assess the risk posed by these viruses at the poultry-wild bird and the avian-human interfaces and to investigate the potential lateral spread between infected premises, a key factor in understanding the threat to the commercial sector.

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens.

The 2021/2022 epizootic of high pathogenicity avian influenza (HPAIV) remains one of the largest ever in the UK, being caused by a clade 2.3.4.4b H5N1 HPAIV. This epizootic affected more than 145 poultry premises, most likely through independent incursion from infected wild birds, supported by more than 1700 individual detections of H5N1 from wild bird mortalities. Here an H5N1 HPAIV, representative of this epizootic (H5N1-21), was used to investigate its virulence, pathogenesis and transmission in layer chickens and Pekin ducks, two species of epidemiological importance. We inoculated both avian species with decreasing H5N1-21 doses. The virus was highly infectious in ducks, with high infection levels and accompanying shedding of viral RNA, even in ducks inoculated with the lowest dose, reflecting the strong waterfowl adaptation of the clade 2.3.4.4 HPAIVs. Duck-to-duck transmission was very efficient, coupled with high environmental contamination. H5N1-21 was frequently detected in water sources, serving as likely sources of infection for ducks, but inhalable dust and aerosols represented low transmission risks. In contrast, chickens inoculated with the highest dose exhibited lower rates of infection compared to ducks. There was no evidence for experimental H5N1-21 transmission to any naive chickens, in two stocking density scenarios, coupled with minimal and infrequent contamination being detected in the chicken environment. Systemic viral dissemination to multiple organs reflected the pathogenesis and high mortalities in both species. In summary, the H5N1-21 virus is highly infectious and transmissible in anseriformes, yet comparatively poorly adapted to galliformes, supporting strong host preferences for wild waterfowl. Key environmental matrices were also identified as being important in the epidemiological spread of this virus during the continuing epizootic.

Relationship between ethnicity and multidisciplinary intervention for young people with rheumatic and musculoskeletal diseases.

Introduction: There is growing recognition of the impact of societal factors on health throughout a patient's lifespan. The COVID-19 pandemic has exposed the impact of racial disparity on health outcomes. Aims: We aimed to investigate the association between ethnicity and the multidisciplinary team (MDT) interventions for young people (YP) with complex care needs. Method: This retrospective, single-centre, cross-sectional study was conducted within the department of adolescent and young adult rheumatology at University College Hospital, London, between August 2019 and August 2021. We extracted demographic, clinical and laboratory data. The index of multiple deprivation was extracted from the Office for National Statistics database. R software was used for analysis. Results: We identified 310 YP referred to the MDT with a median age of 18 years (interquartile range 17-19). The female patient to male patient ratio was 2.4. Over a third of our cohort were from deprived areas. Comparison between Black, Asian and minority ethnic (BAME) and White ethnic groups revealed significant differences in terms of referral for pain optimisation (p=0.006), social support (p<0.00001), and adherence and non-clinic attendance (p=0.0004). Conclusion: Our findings reveal the importance of quality data for early identification and support of vulnerable YP, particularly those from BAME communities.

Skeletal Ring Contractions via I(I)/I(III) Catalysis: Stereoselective Synthesis of cis-α,α-Difluorocyclopropanes.

The clinical success of α,α-difluorocyclopropanes, combined with limitations in the existing synthesis portfolio, inspired the development of an operationally simple, organocatalysis-based strategy to access cis-configured derivatives with high levels of stereoselectivity (up to >20:1 cis:trans). Leveraging an I(I)/I(III)-catalysis platform in the presence of an inexpensive HF source, it has been possible to exploit disubstituted bicyclobutanes (BCBs) as masked cyclobutene equivalents for this purpose. In situ generation of this strained alkene, enabled by Brønsted acid activation, facilitates an unprecedented 4 → 3 fluorinative ring contraction, to furnish cis-α,α-difluorinated cyclopropanes in a highly stereoselective manner (up to 88% yield). Mechanistic studies are disclosed together with conformational analysis (X-ray crystallography and NMR) to validate cis-α,α-difluorocyclopropanes as isosteres of the 1,4-dicarbonyl moiety. Given the importance of this unit in biology and the foundational no → π* interactions that manifest themselves in this conformation (e.g., collagen), it is envisaged that the title motif will find application in focused molecular design.

Emergence of High Pathogenicity Avian Influenza Virus H5N1 Clade 2.3.4.4b in Wild Birds and Poultry in Botswana.

Numerous outbreaks of high-pathogenicity avian influenza (HPAI) were reported during 2020-2021. In Africa, H5Nx has been detected in Benin, Burkina Faso, Nigeria, Senegal, Lesotho, Namibia and South Africa in both wild birds and poultry. Botswana reported its first outbreak of HPAI to the World Organisation for Animal Health (WOAH) in 2021. An H5N1 virus was detected in a fish eagle, doves, and chickens. Full genome sequence analysis revealed that the virus belonged to clade 2.3.4.4b and showed high identity within haemagglutinin (HA) and neuraminidase proteins (NA) for viruses identified across a geographically broad range of locations. The detection of H5N1 in Botswana has important implications for disease management, wild bird conservation, tourism, public health, economic empowerment of vulnerable communities and food security in the region.

Robustness of NanoBiT luciferase complementation technology in the presence of widely used kinase inhibitors.

Bioluminescence assays using luciferase enzymes are widely used in research to monitor gene expression and an array of other cell properties, and split luciferase enzymes can be used to measure protein interactions in biochemical assays and in living cells. When these methods are employed in chemical library screening efforts, it is vital that the activity of the luciferase enzyme itself is not strongly influenced by library components. Here, we developed a NanoBiT split luciferase assay to measure phosphorylation of Histone H3 peptides and used it to test the robustness of split luciferase to interference from two libraries of commonly used kinase inhibitors, including the Kinase Chemogenomic Set (KCGS). We found that NanoBiT luciferase is not significantly affected by the great majority of kinase inhibitors tested. However, the weak inhibition observed for a small minority of kinase inhibitors encourages the inclusion of suitable controls in NanoBiT (or NanoLuc) assays.

Intranasal Treatment of Ferrets with Inert Bacterial Spores Reduces Disease Caused by a Challenging H7N9 Avian Influenza Virus.

Background: Influenza is a respiratory infection that continues to present a major threat to human health, with ~500,000 deaths/year. Continued circulation of epidemic subtypes in humans and animals potentially increases the risk of future pandemics. Vaccination has failed to halt the evolution of this virus and next-generation prophylactic approaches are under development. Naked, "heat inactivated", or inert bacterial spores have been shown to protect against influenza in murine models. Methods: Ferrets were administered intranasal doses of inert bacterial spores (DSM 32444K) every 7 days for 4 weeks. Seven days after the last dose, the animals were challenged with avian H7N9 influenza A virus. Clinical signs of infection and viral shedding were monitored. Results: Clinical symptoms of infection were significantly reduced in animals dosed with DSM 32444K. The temporal kinetics of viral shedding was reduced but not prevented. Conclusion: Taken together, nasal dosing using heat-stable spores could provide a useful approach for influenza prophylaxis in both humans and animals.

Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis.

Protein kinases that phosphorylate histones are ideally-placed to influence the behavior of chromosomes during cell division. Indeed, a number of conserved histone phosphorylation events occur prominently during mitosis and meiosis in most eukaryotes, including on histone H3 at threonine-3 (H3T3ph). At least two kinases, Haspin and VRK1 (NHK-1/ballchen in Drosophila), have been proposed to carry out this modification. Phosphorylation of H3 by Haspin has defined roles in mitosis, but the significance of VRK1 activity towards histones in dividing cells has been unclear. Here, using in vitro kinase assays, KiPIK screening, RNA interference, and CRISPR/Cas9 approaches, we were unable to substantiate a direct role for VRK1, or its paralogue VRK2, in the phosphorylation of threonine-3 or serine-10 of Histone H3 in mitosis, although loss of VRK1 did slow cell proliferation. We conclude that the role of VRKs, and their more recently identified association with neuromuscular disease and importance in cancers of the nervous system, are unlikely to involve mitotic histone kinase activity. In contrast, Haspin is required to generate H3T3ph during mitosis.

Association of Food Insecurity with Mental Health Outcomes in Parents and Children.

BACKGROUND: Food insecurity affects 13.7 million US households and is linked to poor mental health. Families shield children from food insecurity by sacrificing their nutritional needs, suggesting parents and children experience food insecurity differentially. OBJECTIVE: To identify the associations of food insecurity and mental health outcomes in parents and children DATA SOURCES: PubMed, Embase, Web of Science, and PsycInfo STUDY ELIGIBILITY CRITERIA: We included original research published in English from January 1990 to June 2020 that examined associations between food insecurity and mental health in children or parents/guardians in the United States. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers screened studies for inclusion. Data extraction was completed by one reviewer and checked by a second. Bias and confounding were assessed using the Agency for Healthcare Research and Quality RTI Item Bank. Studies were synthesized qualitatively, grouped by mental health outcome, and patterns were assessed. Meta-analyses were not performed due to high variability between studies. RESULTS: We included 108 studies, assessing 250,553 parents and 203,822 children in total. Most studies showed a significant association between food insecurity and parental depression, anxiety, and stress, and between food insecurity and child depression, externalizing/internalizing behaviors, and hyperactivity. LIMITATIONS: Most studies were cross-sectional and many were medium- or high-risk for bias or confounding. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Food insecurity is significantly associated with various mental health outcomes in both parents and children. The rising prevalence of food insecurity and mental health problems make it imperative that effective public health and policy interventions address both problems.

'We felt like part of a production system': A qualitative study on women's experiences of mistreatment during childbirth in Switzerland.

INTRODUCTION: Mistreatment during childbirth is an issue of global magnitude that not only violates fundamental human rights but also seriously impacts women's well-being. The purpose of this study was to gain a better understanding of the phenomenon by exploring the individual experiences of women who reported mistreatment during childbirth in Switzerland. MATERIALS AND METHODS: This project used a mixed methods approach to investigate women's experiences of mistreatment during childbirth in general and informal coercion specifically: The present qualitative study expands on the findings from a nationwide online survey on childbirth experience. It combines inductive with theoretical thematic analysis to study the 7,753 comments women wrote in the survey and the subsequent interviews with 11 women who reported being mistreated during childbirth. RESULTS: The women described a wide range of experiences of mistreatment during childbirth in both the survey comments and the interviews. Out of all survey participants who wrote at least one comment (n = 3,547), 28% described one or more experiences of mistreatment. Six of the seven types of mistreatment listed in Bohren and colleagues' typology of mistreatment during childbirth were found, the most frequent of which were ineffective communication and lack of informed consent. Five additional themes were identified in the interviews: Informal coercion, risk factors for mistreatment, consequences of mistreatment, examples of good care, and what's needed to improve maternity care. CONCLUSION: The findings from this study show that experiences of mistreatment are a reality in Swiss maternity care and give insight into women's individual experiences as well as how these affect them during and after childbirth. This study emphasises the need to respect women's autonomy in order to prevent mistreatment and empower women to actively participate in decisions. Both individual and systemic efforts are required to prevent mistreatment and guarantee respectful, dignified, and high-quality maternity care for all.

Multistate Outbreak of SARS-CoV-2 B.1.1.529 (Omicron) Variant Infections Among Persons in a Social Network Attending a Convention - New York City, November 18-December 20, 2021.

On December 2, 2021, the Minnesota Department of Health (MDH) notified CDC of a COVID-19 case caused by sequence-confirmed SARS-CoV-2 B.1.1.529 (Omicron) variant in a Minnesota resident (patient A), the first such case identified in the state and one of the earliest identified in the United States. Patient A had attended a large indoor convention in New York, New York with approximately 53,000 attendees from 52 U.S jurisdictions and 30 foreign countries during November 19-21, 2021, and had close contact† during 5 days with 29 fellow attendees. The convention required attendees to have received ≥1 COVID-19 vaccine dose and enforced mask-use while indoors. On November 22, these close contact attendees were directly and immediately notified by patient A of their exposure to SARS-CoV-2, and they sought testing over the next few days while quarantined or isolated. As part of the larger investigation into SARS-CoV-2 transmission at the convention, a subinvestigation was conducted during December by CDC, MDH, and respective state and local health departments to characterize the epidemiology of Omicron variant infection among this group of close contacts and determine the extent of secondary household transmission. Among 30 convention attendees that included patient A (the index patient) and the 29 other close contacts, 23 were interviewed, among whom all were fully vaccinated, including 11 (48%) who had received a booster dose; all 23 sought testing, and 16 (70%) received a positive SARS-CoV-2 test result. Fewer attendees who had received a booster dose before the convention received a positive test result (six of 11) compared with those who had not received a booster dose (10 of 12). The 16 attendees with positive test results had a total of 20 household contacts, 18 of whom sought testing after exposure; six received a positive test result for SARS-CoV-2. None of the persons with positive test results was hospitalized or died. There was limited convention-associated transmission identified outside of this cluster; the larger investigation included cases of both SARS-CoV-2 B.1.617.2 (Delta) and Omicron, and all Omicron cases were associated with this group (1). Data from this investigation reinforces the importance of COVID-19 booster doses in combination with early notification and other multicomponent prevention measures to limit transmission and prevent severe illness from Omicron and other SARS-CoV-2 variants.

Detection of Highly Pathogenic Avian Influenza Virus H5N1 Clade 2.3.4.4b in Great Skuas: A Species of Conservation Concern in Great Britain.

The UK and Europe have seen successive outbreaks of highly pathogenic avian influenza across the 2020/21 and 2021/22 autumn/winter seasons. Understanding both the epidemiology and transmission of these viruses in different species is critical to aid mitigating measures where outbreaks cause extensive mortalities in both land- and waterfowl. Infection of different species can result in mild or asymptomatic outcomes, or acute infections that result in high morbidity and mortality levels. Definition of disease outcome in different species is of great importance to understanding the role different species play in the maintenance and transmission of these pathogens. Further, the infection of species that have conservation value is also important to recognise and characterise to understand the impact on what might be limited wild populations. Highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b has been detected in great skuas (Stercorarius skua) across different colonies on islands off the shore of Scotland, Great Britain during summer 2021. A large number of great skuas were observed as developing severe clinical disease and dying during the epizootic and mortalities were estimated to be high where monitored. Of eight skuas submitted for post-mortem examination, seven were confirmed as being infected with this virus using a range of diagnostic assays. Here we overview the outbreak event that occurred in this species, listed as species of conservation concern in Great Britain and outline the importance of this finding with respect to virus transmission and maintenance.

Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice.

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points. RESULTS: Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment. CONCLUSIONS: These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.

Growth of Pediatric Refugees after Resettlement to the Southeastern United States.

OBJECTIVE: To compare weight status and body mass index z-scores (BMIz) of refugee children upon arrival to the Southeastern US and after resettlement with age- and sex-matched controls of nonrefugee children. METHODS: We identified refugee children resettled between July 2014 and June 2018 to Forsyth County, NC. Refugees were assigned age- and sex-matched controls (3 controls:1 refugee) who received care at the same health care site, were Medicaid insured, and had height and weight recorded at time of their matched refugee's resettlement plus at least 2 additional visits. BMI and BMIz were calculated. Pearson chi-square test assessed differences in weight status at the time of refugee resettlement and at the last measured time point. Multilevel linear mixed-effects regression models assessed change in BMIz by refugee status, adjusting for sex, race/ethnicity, age, and time since resettlement. RESULTS: This study examined 139 pediatric refugees and 417 nonrefugee controls; 46% were female. At the time of resettlement, refugees had a higher rate of underweight (3.3%  vs 1.9%), higher rate of healthy weight (68.9% vs 48.2%), and lower rate of overweight/obesity (27.8% vs 50%), compared to controls P < .001. At the last available time point, compared to controls, refugees had higher rates of underweight (3.3% vs 3.0%) and healthy weight (69.5% vs 54.2%) and lower rates of overweight/obesity (27.2%  vs 42.7%), P = .005. Refugees had a lower predicted BMIz compared with controls (adjusted ß: -0.78; 95%  confidence interval -0.91, -0.66). CONCLUSIONS: Resettled pediatric refugees were found to have significantly lower predicted BMIz than their age- and sex-matched nonrefugee controls.

Expanding organofluorine chemical space: the design of chiral fluorinated isosteres enabled by I(i)/I(iii) catalysis.

Short aliphatic groups are prevalent in bioactive small molecules and play an essential role in regulating physicochemistry and molecular recognition phenomena. Delineating their biological origins and significance have resulted in landmark developments in synthetic organic chemistry: Arigoni's venerable synthesis of the chiral methyl group is a personal favourite. Whilst radioisotopes allow the steric footprint of the native group to be preserved, this strategy was never intended for therapeutic chemotype development. In contrast, leveraging H → F bioisosterism provides scope to complement the chiral, radioactive bioisostere portfolio and to reach unexplored areas of chiral chemical space for small molecule drug discovery. Accelerated by advances in I(i)/I(iii) catalysis, the current arsenal of achiral 2D and 3D drug discovery modules is rapidly expanding to include chiral units with unprecedented topologies and van der Waals volumes. This Perspective surveys key developments in the design and synthesis of short multivicinal fluoroalkanes under the auspices of main group catalysis paradigms.

Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.