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Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Substance use disorders (SUDs) represent a critical public and occupational health issue. Therefore, understanding the process of SUD recovery has become an issue of growing importance among substance use and recovery professionals. Nonetheless, despite the acknowledged importance of employment for SUD recovery, little conceptual or empirical work exists on how the workplace might support or undermine SUD recovery. In this article, we address this limitation in several ways. First, to promote a better understanding of SUD recovery for occupational health researchers, we provide a brief overview of the nature of a SUD, prior definitions of SUD recovery, and general themes associated with the recovery process. Second, we develop a working definition of workplace supported recovery. Third, we present a heuristic conceptual model showing how the workplace might impact the SUD recovery process. Fourth, using this model and research from the substance use and occupational health literatures, we develop a series of general research propositions. These propositions highlight broad directions requiring more detailed conceptualization and empirical research to understand better how work conditions may support or undermine the process of employee SUD recovery. Our overarching goal is to motivate innovative conceptualization and research on workplace supported recovery from SUDs. Such research may inform the development and evaluation of workplace interventions and policies supporting SUD recovery and highlight the benefits of workplace supported SUD recovery for employees, employers, and communities. Research on this issue may allow occupational health researchers to impact a significant societal and occupational health issue.

Acclimation through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms’ performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant properties. They are light-dependent with a sessile and modular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes at the local level. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled with significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally alter our understanding of how cnidarian invertebrates repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.

Objectives The impact of posttraumatic cognitions on the development and maintenance of posttraumatic stress symptoms (PTSS) is understudied among children and adolescents who have experienced commercial sexual exploitation/trafficking (CSE/T). The objectives of this study were to (1) explore posttraumatic cognitions among help-seeking young people aged 11-19 who have experienced CSE/T; (2) determine whether experiencing direct violence, witnessing violence, polyvictimization (ie, multiple exposures to different categories of potentially traumatic events), or demographic characteristics differentially affect whether these young people meet clinical criteria for posttraumatic cognitions using established cutoffs; and (3) explore associations between posttraumatic cognitions and PTSS among young people who have experienced CSE/T. Methods This study is a secondary analysis of a baseline cross-sectional survey of 110 young people with substantiated CSE/T experiences who started trauma-focused cognitive behavioral therapy (mean [SD] age = 15.8 [1.5]) from August 1, 2013, through March 31, 2020, in a southeastern US state. We used descriptive statistics, adjusted modified Poisson regression, and adjusted linear regression to test study objectives. Results Fifty-seven of 110 (51.8%) young people aged 11-19 met clinical criteria for posttraumatic cognitions. Increased age and a greater number of trauma categories experienced were significantly associated with meeting clinical criteria for posttraumatic cognitions. On average, higher posttraumatic cognition scores were associated with higher PTSS scores, controlling for demographic characteristics (β = 0.95; 95% CI, 0.64-1.26). Conclusions These findings underscore the importance of assessing comprehensive trauma history and PTSS of young people who have experienced CSE/T, with added usefulness of measuring cognitive appraisals to inform a therapeutic treatment plan. Measuring cognitive appraisals that may influence PTSS and therapeutic success can ensure an effective public health response for this population.

Global climate change is increasing the frequency and severity of extreme climatic events (ECEs) which may be especially detrimental during late-winter when many species are surviving on scarce resources. However, monitoring animal populations relative to ECEs is logistically challenging. Crowd-sourced datasets may provide opportunity to monitor species' responses to short-term chance phenomena such as ECEs. We used 14 years of eBird-a global citizen science initiative-to examine distribution changes for seven wintering waterfowl species across North America in response to recent extreme winter polar vortex disruptions. To validate inferences from eBird, we compared eBird distribution changes against locational data from 362 GPS-tagged Mallards (Anas platyrhynchos) in the Mississippi Flyway. Distributional shifts between eBird and GPS-tagged Mallards were similar following an ECE in February 2021. In general, the ECE affected continental waterfowl population distributions; however, responses were variable across species and flyways. Waterfowl distributions tended to stay near wintering latitudes or moved north at lesser distances compared with non-ECE years, suggesting preparedness for spring migration was a stronger "pull" than extreme weather was a "push" pressure. Surprisingly, larger-bodied waterfowl with grubbing foraging strategies (i.e., geese) delayed their northward range shift during ECE years, whereas smaller-bodied ducks were less affected. Lastly, wetland obligate species shifted southward during ECE years. Collectively, these results suggest specialized foraging strategies likely related to resource limitations, but not body size, necessitate movement from extreme late-winter weather in waterfowl. Our results demonstrate eBird's potential to monitor population-level effects of weather events, especially severe ECEs. eBird and other crowd-sourced datasets can be valuable to identify species which are adaptable or vulnerable to ECEs and thus, begin to inform conservation policy and management to combat negative effects of global climate change.

Federal, state, and private entities manage seasonal flooded, shallow wetlands to provide food and other habitat resources for wetland-dependent migratory birds, including migrating and wintering waterfowl. Individual National Wildlife Refuges managed by the U.S. Fish and Wildlife Service annually monitor seed production in moist-soil wetlands to track performance relative to regional foraging habitat objectives and to evaluate local habitat management activities. The National Wildlife Refuge System does not currently have a standard sampling protocol, and thus seeks a reliable rapid assessment method for estimating seed production to achieve standardized estimates and to avoid inconsistencies in data collection, metrics used, and usefulness of the monitoring efforts. We compared seed yield estimates derived from a suite of commonly used seed production assessment methods with those from soil core samples across six National Wildlife Refuges in the southeastern United States. The most parsimonious model included only common plant species and a single visual assessment of overall coverage (1–5) and seed quality (1–4) for each moist-soil unit (r2adj = 0.71). Generally, models that included only common plant species and a visual estimate of seed yield for moist-soil wetlands overall had greater support than models that included all plant species and those that included data from subplots (n = 10) nested within moist-soil wetlands. Experience level of observer had a moderate effect on accuracy (r2mar = 0.20) and geographic range increased variation in overall seed yield estimates within moist-soil wetlands. Notably, we found that similar indices developed in different geographic regions performed well across the Southeast, but a widely used index based on estimates of seed yield for individual plant species performed poorly in this study. Standardizing the use of a single, efficient, and reliable method to estimate seed abundance in moist-soil wetlands will provide wetland mangers the ability to consistently estimate performance relative to objectives, evaluate management actions, and track trends on National Wildlife Refuges in the southeastern United States.

Background: Patients with higher socioeconomic status (SES) are overrepresented in NCI-sponsored cancer clinical trials (CCT). Inadequate access, social and cultural barriers have been described as reasons for poor accrual of patients with low SES into clinical trials. Racial minorities including African Americans (AA) and Hispanics are underrepresented in CCT and often experience issues related to lack of access. On the other hand, survey studies throughout United States suggest equal willingness for participation in CCT among all racial categories. When access to CCT is not a barrier to enrollment, the rate of CCT participation by Racial and Ethnic minorities with low SES is not well studied. Methods: We performed a retrospective review of the database of new patients screened for breast CCT at Dan L Duncan Comprehensive Cancer Center (DLDCCC). DLDCCC is an ideal venue for studies on clinical trial diversity because it provides cancer care to two very different patient demographics: 1) Smith Clinic is a Harris Health System (HHS) cancer clinic where a majority of the patients are of low SES; half of our patients earn less than $25,000 annually, 60% are uninsured using a county financial assistance program called “Gold Card”, 65% are unable to speak proficient English, and 52% are Hispanic, 25% AA, 9% Caucasian and 5% Asian, 2) Baylor St Luke’s Medical Center (BSLMC) serves predominantly Caucasian patients with >95% of the patients having federal or commercial insurance. Cancer clinical trials are available at both sites, and all patients across the two clinics have equal opportunity for enrollment. The database dates back to 5/2015 and includes 3,084 patients. Using the chi-squared test, we compared the rate of trial availability, trial eligibility and enrollment for breast CCT between two patient populations receiving care at Smith clinic vs. BSLMC. We tabulated the rate of trial participation decline at each clinic per year from 5/2015 to 6/2021. The study had IRB approval from Baylor College of Medicine.Results: Among the 3,084 new-to-practice patients, 1,664 patients were seen at BSLMC and 1,420 were seen at Smith Clinic. Clinical trials were available for 758 (53.4%) patients at Smith clinic and 742 (44.6%) patients at BSLMC, p Citation Format: Maryam Nemati Shafaee, Emily L Podany, Katherine Sanchez, Nicole Higashiyama, Valentina Hoyos, Liz Binu Micheal, Kristen Otte, Anne Pavlick, Julie Nangia, Alphi Kuriakose, Kent C Osborne, Maria Jibaja-Weiss, Matthew J Ellis, Shaun Bulsara, Mothaffar Rimawi. Breast cancer clinical trial participation rate among patients of low socioeconomic status at a comprehensive cancer center [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-14-02.

Background:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, disproportionally affecting African American and Hispanic patients, and germline BRCA1/2 mutation carriers. Prognosis of relapsed, metastatic disease is extremely poor and effective well-tolerated therapies are urgently needed. Our collaborators have discovered that TNBCs often lose feedback control of receptor tyrosine kinases (RTKs) including PDGFR and MET, locking these receptors in a chronically active state. These receptors share a common negative regulator called Protein Tyrosine Phosphatase, Non-Receptor Type 12 (PTPN12). Baylor investigators have shown that PTPN12- deficient TNBCs may be responsive to combined RTK inhibition. Sitravatinib is a spectrum selective RTK inhibitor that has shown strong antitumor activity in patient derived xenografts (PDXs) of TNBC with low levels of PTPN12. We have therefore designed a phase II, multi-institution, two cohort trials to evaluate the efficacy of sitravatinib in patients with metastatic TNBC (mTNBC). Methods: Patients with diagnosis of mTNBC who have received at least one line of chemotherapy +/- atezolizumab for advanced disease would be considered for enrollment. Patients would need to have tissue from metastatic site available for evaluation or agree to undergo biopsy if banked tumor tissue is not available. Sitravatinib at 100 mg daily, the recommended phase 2 dose for sitravatinib monotherapy, will be started at the initiation of the study and continued until progression or unacceptable toxicity. The study will employ a modified optimal Simon’s two stage design. Patients will be recruited into two cohorts: PTPN12 low or PTPN12 high/normal cohorts simultaneously and independently. Seven patients will be enrolled to each arm during the first stage. After the first stage, depending on the observed number of responses, the study will proceed to the 2nd stage. The primary endpoint is progression-free survival status at 24 weeks (PFS24). Current Trial status: The trial is funded by Mirati Therapeutics and opened to enrollment at Dan L Duncan Comprehensive Cancer Center (DLDCCC) clinics as of 6/8/21. Trial is due to open at UT Southwestern Dallas by 11/2021. The correlative science is funded by an institutional SPORE grant. Conclusion: This trial aims to show that sitravatinib is safe and to investigate whether it could be a treatment option in mTNBC. Citation Format: Maryam Nemati Shafaee, Kristen Otte, Nicholas J Neill, Kent C Osborne, Thomas F Westbrook, Susan Hilseneck, Matthew J Ellis. A phase 2 study of sitravatinib in metastatic, pre-treated, triple negative breast cancer, NCT # 04123704 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-28-01.

List of differentially present metabolites. The table lists fold change value of metabolites differentially detected in CAF co-cultures compared to separately cultured cells in at least one of the cell lines. Bold font indicates statistically significant (p

Classification of METABRIC cohort into prognostic groups. The file has three worksheets. Patient Grouping and Scores: Summary of patient classification and stromal and immune scores from ESTIMATE. Gene Signatures: list of genes in each gene signature. Multivariate Analysis models: contributions of each clinical covariate to multivariate cox proportional hazards models.

List of the inhibitors tested for the ability to overcome CAF mediated resistance to lapatinib.

Using a three-dimensional coculture model, we identified significant subtype-specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAF). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Fibroblasts from normal breast tissues and stromal cultures of brain metastases of breast cancer had similar effects as CAFs. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo, including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance. Cancer Res; 76(22); 6495–506. ©2016 AACR.

List of differentially expressed genes. The table lists values of fold changes in gene expression for the genes, up or down regulated in the indicated breast cancer cell lines cultured in the presence of CAFs compared to breast cancer cells cultured separately.

Associations between molecular features and clinical outcome. Patient outcome and changes in pSTAT3+, SMA+, Ki67+ cells and distance between Ki67+&SMA+ cells are indicated. Initial values from Day 0 where possible, otherwise Day 1. For continuous data, increase or decrease of at least 5% of initial value used as a threshold. Changes computed as Time0 - mean (Time 2,4,6 weeks). Outcome is percentage shrinkage of tumor at week 6.

Supplementary Figures, Detailed Methods, and Supplementary References

Home health aides (HHAs) are a vital workforce essential to meet the complex care needs of the persons living with dementia (PLWD) who remain at home. Care plans for PLWD in the home healthcare setting should incorporate HHAs perspectives. We sought to understand HHAs’ perspectives about their information needs in caring for PLWD, from June to August 2020, semi-structured interviews telephone interviews (n = 25) with English and Spanish-speaking HHAs with limited English proficiency in the New York metropolitan area. Interviews were audio-recorded, transcribed verbatim and transcripts were analyzed using conventional content analysis. Four key themes emerged reflective of information needs of HHAs caring for PLWD: (1) ambiguities of scope of HHA tasks related to medication management; (2) clinical information needs of HHAs; (3) dementia-related concerns; and (4) going above and beyond. Findings from this research can guide efforts to develop dementia-specific care plans, and training to support the HHA workforce caring for the growing population of PLWD.

Objective: To investigate medication factors and patient characteristics associated with readmissions following alcohol-related hospitalizations. Patients and Methods: Adult patients admitted from September 1, 2016, through August 31, 2019, who had an alcohol-related hospitalization were identified through electronic health records. Patient characteristics and medications of interest administered during hospitalization or prescribed at discharge were identified. Medications of interest included US Food and Drug Administration–approved medications for alcohol use disorder, benzodiazepines, barbiturates, gabapentin, opioids, and muscle relaxants. The primary outcome was to identify medications and patient factors associated with 30-day alcohol-related readmission. Secondary outcomes included medications and patient characteristics associated with multiple alcohol-related readmissions within a year from the index admission (ie, two or more readmissions) and factors associated with 30-day all-cause readmission. Results: Characteristics of the 932 patients included in this study associated with a 30-day alcohol-related readmission included younger age, severity of alcohol withdrawal, history of psychiatric disorder, marital status, and the number of prior alcohol-related admission in the previous year. Benzodiazepine or barbiturate use during hospitalization or upon discharge was associated with 30-day alcohol-related readmission (P=.006). Gabapentin administration during hospitalization or upon discharge was not associated with 30-day alcohol-related readmission (P=.079). Conclusion: The findings reinforce current literature identifying patient-specific factors associated with 30-day readmissions. Gabapentin use was not associated with readmissions; however, there was an association with benzodiazepine/barbiturate use.

Background Every year, many thousands of travellers return to the United Kingdom (UK) from visits to other countries and some will become unwell due to infections acquired abroad. Many imported infections have similar clinical presentations, such as fever and myalgia, so diagnostic testing is an important tool to improve patient management and outcomes. The aim of this study was to examine the demographics, travel history, presenting symptoms and diagnostic outcomes of referrals to the UK’s specialist diagnostic Rare & Imported Pathogens Laboratory (RIPL) for the period 2015–2020. Methods Anonymised clinical and laboratory data were extracted from RIPL’s Laboratory Information Management System and cleaned prior to descriptive analysis of the data. Travel history data were mapped to one of eight world regions, whereas symptom data were categorised into presenting syndromes. Diagnostic data were categorised as either positive, equivocal or negative. Results During the period 2015–2020, RIPL received 73 951 samples from 53 432 patients suspected of having infections that are rare in the UK. The most common age group for unwell returning travellers was 30–39 years and the most commonly reported travel destination was Southern and SE Asia. Dengue virus was the most diagnosed infection overall, followed by chikungunya, Zika, leptospirosis and spotted fever group Rickettsia. Dengue virus was among the top three most frequent diagnoses for all world regions except Europe and represented 62.5% of all confirmed/probable diagnoses. Conclusions None of the top five infections diagnosed by RIPL in travellers are vaccine-preventable, therefore understanding traveller demographics, destination-specific risk factors and encouraging preventative behaviours is the best available strategy to reduce the number of returning travellers who become infected. Prompt referral of acute samples with a detailed travel history, including purpose of travel and activities undertaken as well as dates and destinations can be a valuable tool in designing public health interventions and diagnostic algorithms.

While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Here, we directly compared CD11c + T-bet + ABCs using models of Epstein-Barr virus (EBV), gammaherpesvirus 68 (γHV68), multiple sclerosis (MS), and experimental autoimmune encephalomyelitis (EAE), and found that each drives the ABC population to opposing phenotypes. EBV infection has long been implicated in MS, and we have previously shown that latent γHV68 infection exacerbates EAE. Here, we demonstrate that ABCs are required for γHV68-enhanced disease. We then show that the circulating ABC population is expanded and phenotypically altered in people with relapsing MS. In this study, we show that viral infection and autoimmunity differentially affect the phenotype of ABCs in humans and mice, and we identify ABCs as functional mediators of viral-enhanced autoimmunity.

A plethora of studies have established the importance of eosinophils in protective immunity against infections and in allergy. In this issue of Immunity, Ignacio et al. (2022) define a vital for eosinophils in coordinating a microbiota-epithelial-immune axis that maintains intestinal homeostasis.

Suicide is the second leading cause of death among adolescents in the U.S., and risk factors include child maltreatment (CM), especially physical and emotional abuse, and in-home firearm availability ('availability'). However, research examining availability among adolescent populations at-risk for CM is limited. This study examines availability in this population, the association between CM and availability, and availability among adolescents experiencing suicidal ideation. A multivariable modified Poisson regression model assessed the relationship between CM by age 12 and availability at age 14 using data from the Longitudinal Studies of Child Abuse and Neglect (n = 1,354 families). Approximately 11.61% of adolescents reported availability, and physical abuse increased the risk of availability (aRR = 1.94; 95% CI [1.22, 3.08]). Over one-quarter (27.50%) of adolescents with suicidal ideation at age 16 reported availability. Child welfare-involved families are often referred to interventions. Future research and prevention efforts should explore augmentation of these programmes with firearm safe storage guidance.

The authors present a new approach to show how interdisciplinary collaborations among a group of institutions can provide a unique opportunity for students to engage across the science-policy nexus using the framework of the Sustainable Development Goals and the United Nations Framework Convention on Climate Change. Through collaboration across seven higher education institutions in the United States and Australia, virtual student research teams worked together across disciplines.

Ubiquitin and ubiquitin-like proteins (UBLs) function as critical post-translational modifiers in the maintenance of genome stability. Ubiquitin/UBL-conjugating enzymes (E2s) are responsible, as part of a wider enzymatic cascade, for transferring single moieties or polychains of ubiquitin/UBLs to one or multiple residues on substrate proteins. Recent advances in structural and mechanistic understanding of how ubiquitin/UBL substrate attachment is orchestrated indicate that E2s can exert control over chain topology, substrate-site specificity, and downstream physiological effects to help maintain genome stability. Drug discovery efforts have typically focussed on modulating other members of the ubiquitin/UBL cascades or the ubiquitin-proteasome system. Here, we review the current standing of E2s in genome stability and revisit their potential as pharmacological targets for developing novel anti-cancer therapies.

SummaryDietary fibers are potent modulators of immune responses that can restrain inflammation in multiple disease contexts. However, dietary fibers encompass a biochemically diverse family of carbohydrates, and it remains unknown how different fiber sources influence immunity. In a head-to-head comparison of four different high-fiber diets, we demonstrate a unique and potent ability of guar gum to reduce neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a T cell-mediated mouse model of multiple sclerosis. CD4+ T cells from guar gum-fed mice have blunted Th1-skewing, reduced migratory capacity, and limited activation and proliferative capabilities. These changes are not explained by guar gum-specific alterations to the microbiota at the 16S rRNA level, nor by specific alterations in short chain fatty acids. These findings demonstrate specificity in the host response to fiber sources, and define a new pathway of fiber-induced CD4+ T cell immunomodulation that protects against pathologic neuroinflammation.

Millions of older Americans receive nurse practitioner (NP)-provided home based primary care (HBPC). Little is known about how state scope-of- practice (SOP) laws may impact use of NP-home visits. Using 2017 Centers for Medicare and Medicaid Services Provider Utilization and Payment Data Public Use File (PUF), we examined the impact of state SOP laws on the use of NP-home visits. The PUF file was merged with the 2017 American Community Survey to assess area-level median income. Over 4.4 million home visits were provided to 1.6 million Medicare beneficiaries. NPs represented the largest share of providers (47.5%). In states with restricted SOP laws, compared to NPs, physicians and physician assistants had higher odds of providing HBPC. In states with reduced SOP laws, compared to NPs, physicians and PAs had decreased odds of providing HBPC. Our study provides evidence that SOP restrictions are associated with decreased utilization of NP-provided HBPC.

Neurons of the enteric nervous system (ENS) have limited regenerative capacity, and damage to these cells can cause neuropathies. In a recent issue of Cell, Ahrends et al. (2021) demonstrate that muscularis macrophages integrate distinct signals from diverse intestinal infections to protect ENS neurons from subsequent pathogenic insult.

Background: While pain is the hallmark of sickle cell disease (SCD), healthcare personnel are often ill-equipped to adequately treat patients who present in vaso-occlusive crisis (VOC). Although symptom severity varies from individual to individual, SCD is characterized by intervallic pain as a result of oxygen deprivation in tissues and organs. Regardless of pain severity, SCD patients are often viewed as drug seekers by healthcare personnel who have concerns regarding patient s’ dependence on opioids which may lead to addiction. The objective was to assess the types and amount of opioids used to treat VOC in comparison to Centers for Disease Control opioid prescription guidelines. Methods: Literature search was conducted using CINAHL, PubMed, the Cochrane Library, Web of Science and hand search. Data were analyzed from 1999 to 2018. Randomized trials, observational, and case studies involved hospitalized adults with SCD who were prescribed opioids to treat VOC. Quality assessment was conducted using Downs and Black checklist. Meta-analysis was not conducted. Results: Five studies were conducted in the USA, Arabia and the Netherlands, and the USA and Canada were included. Participants were treated with either morphine or morphine milligram equivalent (MME). No study used the same method of opioid administration. Conclusions: Patients with SCD who are hospitalized secondary to VOC mostly received opioids for pain well within the Centers for Disease Control and Prevention prescription guidelines. No uniform method exists. Additional research is warranted. J Hematol. 2021;10(2):46-52 doi: https://doi.org/10.14740/jh828

This study explores the types and extent of potentially traumatic events that youth who have experienced commercial sexual exploitation and trafficking (CSE/T) report, and how these experiences influence mental health. CSE/T youth (N = 110, 11-19 years old) referred to Trauma-Focused Cognitive Behavioral therapists affiliated with Project Intersect provided self-report data between August 2013 and March 2020 at the start (baseline), mid-point, and completion of therapeutic services. This study focuses on the baseline data collected. Bivariate relationships were analyzed, and where bivariate associations were statistically significant, associations were assessed in adjusted regression models. Two logistic regressions were performed: one for the adjusted associations between types of potentially traumatic events reported by CSE/T youth and the outcome PTSD, and a second for the outcome emotional distress. Results indicated that polytrauma was significantly associated with PTSD diagnosis among CSE/T youth. Direct violence victimization and polytrauma were significantly associated with CSE/T youth emotional distress. Results inform behavioral medicine practitioner considerations for how to appropriately assess the potentially traumatic experiences of CSE/T youth, and how these experiences may differentially impact the mental health presentations of youth in clinical treatment. Effective treatment may include precision-based customization of evidence-based practices to ensure that the diverse traumatic experiences and related symptomatology of CSE/T youth are effectively addressed.

Autoimmune disorders like type 1 diabetes (T1D) are complex diseases caused by numerous factors including both genetic variance and environmental influences. Two such exogenous factors, intestinal microbial composition and enterovirus infection, have been independently associated with T1D onset in both humans and animal models. Since environmental factors rarely work in isolation, we examined the cross-talk between the microbiome and Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice. We demonstrate that CVB4-infection induced restructuring of the intestinal microbiome prior to T1D onset that was associated with thinning of the mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased detection of circulating and intestinal commensal-reactive antibodies. Notably, the CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, thus implying a mutual “diabetogenic” microbiome. Furthermore, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice was sufficient to enhance T1D susceptibility in naïve NOD recipients. These findings support a model whereby CVB infection disrupts the microbiome and intestinal homeostasis in a way that promotes activation of autoreactive immune cells and T1D.

Intestinal epithelial cells (IECs) serve as both a physical and an antimicrobial barrier against the microbiota, as well as a conduit for signaling between the microbiota and systemic host immunity. As individuals age, the balance between these systems undergoes a myriad of changes due to age-associated changes to the microbiota, IECs themselves, immunosenescence, and inflammaging. In this review, we discuss emerging data related to age-associated loss of intestinal barrier integrity and posit that IEC dysfunction may play a central role in propagating age-associated alterations in microbiota composition and immune homeostasis.

To examine the accuracy between analyzers, the Terumo CDI 500 and the Spectrum Medical Quantum were compared to each other and to the ABL90 FLEX benchtop blood analyzer. Patients were retrospectively identified who underwent cardiac surgery requiring cardiopulmonary bypass between August 1, 2018 and November 1, 2019. Hemoglobin and venous saturation (SvO

Background Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. Methods In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. Findings We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. Interpretation Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease.

Summary Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8–12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of HCV infection is

Spring migration is an energetically demanding event that can impact nutrient dynamics of individuals during the breeding season through carry-over effects. Limited food availability at spring stopover areas may have cross-seasonal effects that adversely impact waterfowl populations. We collected 161 Green-winged Teal (Anas crecca Linnaeus, 1758; hereafter Teal) throughout the Illinois River Valley, USA, during February–April of 2016–2018 and estimated body condition using three condition indices (scaled mass index, scaled wing index, body-size index) for comparison with carcass lipid and protein values. Lipids were 18.3% (95% CI = 1.0%–38.5%) and 21.6% (95% CI = 4.8%–41.0%) greater at locations with moderate (250–600 kg/ha) and high (>600 kg/ha) moist-soil seed densities, respectively, than low moist-seed density (

Recent evidence indicates that viral components of the microbiota can contribute to intestinal homeostasis and protection from local inflammatory or infectious insults. However, host-derived mechanisms that regulate the virome remain largely unknown. In this study, we used colonization with the model commensal murine norovirus (MNV; strain CR6) to interrogate host-directed mechanisms of viral regulation, and we show that STAT1 is a central coordinator of both viral replication and antiviral T cell responses. In addition to restricting CR6 replication to the intestinal tract, we show that STAT1 regulates antiviral CD4(+) and CD8(+) T cell responses and prevents systemic viral-induced tissue damage and disease. Despite altered T cell responses that resemble those that mediate lethal immunopathology in systemic viral infections in STAT1-deficient mice, depletion of adaptive immune cells and their associated effector functions had no effect on CR6-induced disease. However, therapeutic administration of an antiviral compound limited viral replication, preventing virus-induced tissue damage and death without impacting the generation of inflammatory antiviral T cell responses. Collectively, our data show that STAT1 restricts MNV CR6 replication within the intestinal mucosa and that uncontrolled viral replication mediates disease rather than the concomitant development of dysregulated antiviral T cell responses in STAT1-deficient mice. IMPORTANCE The intestinal microbiota is a collection of bacteria, archaea, fungi, and viruses that colonize the mammalian gut. Coevolution of the host and microbiota has required development of immunological tolerance to prevent ongoing inflammatory responses against intestinal microbes. Breakdown of tolerance to bacterial components of the microbiota can contribute to immune activation and inflammatory disease. However, the mechanisms that are necessary to maintain tolerance to viral components of the microbiome, and the consequences of loss of tolerance, are less well understood. Here, we show that STAT1 is integral for preventing escape of a commensal-like virus, murine norovirus CR6 (MNV CR6), from the gut and that in the absence of STAT1, mice succumb to infection-induced disease. In contrast to the case with other systemic viral infections, mortality of STAT1-deficient mice is not driven by immune-mediated pathology. Our data demonstrate the importance of host-mediated geographical restriction of commensal-like viruses.

Underrepresented minority (URM) students in nursing education are essential to address health disparities.To determine barriers and facilitators to success among URM students in nursing education.CINAHL, PubMed, Embase, and PsycINFO were searched for English language research studies published between 1980 and 2020, which focused on barriers and facilitators to success in nursing education in the United States among URM students. Using PRISMA guidelines, 2 reviewers independently reviewed and appraised the quality of relevant articles.Among the 4435 articles surveyed, 14 met inclusion criteria. Most studies were focused on Black and Hispanic/Latinx students, and 71% were qualitative. Barriers included social isolation, caregiving demands, lack of mentorship, and inadequate financial resources. Facilitators included mentorship, positive class and curriculum, family support, financial support, and diverse/inclusive learning environments.URM students face complex barriers to success in nursing education. Addressing these barriers requires a multilevel approach.

Using the nationally representative sample from the United States in the 2012 Programme for International Student Assessment (N = 7,429 students from 240 schools), I examined the relationship between teacher instructional practices and student mathematics achievement. To account for the multilevel structure of the data with students nested within schools, I used a two-level hierarchical linear model in the data analysis. Teacher instructional practices showed statistically significant effects on student mathematics achievement, even after controlling for socioeconomic status (SES) and sex at the student level and school mean SES and whether the school is public or private at the school level. Furthermore, I found that the relationship between teacher instructional practices and student mathematics achievement varied statistically significantly across schools.

The presence of Salmonella in air of poultry houses has been previously confirmed. Therefore, it is important to investigate the entry of Salmonella into broilers through air. The present study aimed to evaluate different levels of Salmonella Enteritidis aerosol inoculations in broiler chicks for colonization of ceca, trachea, and liver/spleen and persistence over time. In three independent trials, 112 1-d old birds were randomly divided into four groups (n=28/group). On d 1 of age, one group was exposed to an aerosol of sterile saline and the remaining three groups were exposed to an aerosol generated from one of three doses (103, 106, or 109 CFU/mL) of S. Enteritidis inoculum. Aerosol exposure time was 30 min/group and was performed using a nebulizer. On d 3, 7, 14, and 21 of age, ceca, trachea, and liver/spleen were aseptically removed. Ceca were cultured for Salmonella counts (log10 CFU/g) and all tissues were cultured for Salmonella prevalence. All tissues from the control group were Salmonella negative for all sampling days. On sampling d 3 and 7, ceca Salmonella counts were highest (5.14 and 5.11, respectively) when challenged with 109 Salmonella (P ≤ 0.0281). Ceca Salmonella counts increased from d 3 (2.43) to d 7 (4.43), then remained constant when challenged at 103 Salmonella, and counts decreased over time for all other groups. Tissue Salmonella prevalence increased with increasing challenge levels at all sampling timepoints (P ≤ 0.0213). Salmonella prevalence was low (0/18 to 4/18) and did not change over time following 103 Salmonella challenge (P ≥ 0.2394). Prevalence decreased over time in ceca and trachea following 106 and 109 Salmonella challenge (P ≤ 0.0483). Liver/spleen Salmonella prevalence increased from d 3 (13/18) to d 14 (18/18) and then decreased at d 21 (10/18) in birds exposed to an aerosol of 109 Salmonella but remained constant over time for rest of the Salmonella inoculated groups. Overall, this study demonstrated the Salmonella colonization and persistence in different tissues in broilers following exposure to aerosolized Salmonella.