SYK coordinates neuroprotective microglial responses in neurodegenerative disease.

Recent studies have begun to reveal critical roles for the brain's professional phagocytes, microglia, and their receptors in the control of neurotoxic amyloid beta (Aß) and myelin debris accumulation in neurodegenerative disease. However, the critical intracellular molecules that orchestrate neuroprotective functions of microglia remain poorly understood. In our studies, we find that targeted deletion of SYK in microglia leads to exacerbated Aß deposition, aggravated neuropathology, and cognitive defects in the 5xFAD mouse model of Alzheimer's disease (AD). Disruption of SYK signaling in this AD model was further shown to impede the development of disease-associated microglia (DAM), alter AKT/GSK3ß-signaling, and restrict Aß phagocytosis by microglia. Conversely, receptor-mediated activation of SYK limits Aß load. We also found that SYK critically regulates microglial phagocytosis and DAM acquisition in demyelinating disease. Collectively, these results broaden our understanding of the key innate immune signaling molecules that instruct beneficial microglial functions in response to neurotoxic material.

AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment.

Neurodevelopment is characterized by rapid rates of neural cell proliferation and differentiation followed by massive cell death in which more than half of all recently generated brain cells are pruned back. Large amounts of DNA damage, cellular debris, and by-products of cellular stress are generated during these neurodevelopmental events, all of which can potentially activate immune signalling. How the immune response to this collateral damage influences brain maturation and function remains unknown. Here we show that the AIM2 inflammasome contributes to normal brain development and that disruption of this immune sensor of genotoxic stress leads to behavioural abnormalities. During infection, activation of the AIM2 inflammasome in response to double-stranded DNA damage triggers the production of cytokines as well as a gasdermin-D-mediated form of cell death known as pyroptosis1-4. We observe pronounced AIM2 inflammasome activation in neurodevelopment and find that defects in this sensor of DNA damage result in anxiety-related behaviours in mice. Furthermore, we show that the AIM2 inflammasome contributes to central nervous system (CNS) homeostasis specifically through its regulation of gasdermin-D, and not via its involvement in the production of the cytokines IL-1 and/or IL-18. Consistent with a role for this sensor of genomic stress in the purging of genetically compromised CNS cells, we find that defective AIM2 inflammasome signalling results in decreased neural cell death both in response to DNA damage-inducing agents and during neurodevelopment. Moreover, mutations in AIM2 lead to excessive accumulation of DNA damage in neurons as well as an increase in the number of neurons that incorporate into the adult brain. Our findings identify the inflammasome as a crucial player in establishing a properly formed CNS through its role in the removal of genetically compromised cells.

Pandemic-related challenges accessing food and primary healthcare among sex workers during the COVID-19 pandemic: findings from a community-based cohort in Vancouver, Canada.

INTRODUCTION: Globally, the COVID-19 pandemic upended healthcare services and created economic vulnerability for many. Criminalization of sex work meant sex workers were largely ineligible for Canada's government-based financial pandemic relief, the Canadian Emergency Response Benefit. Sex workers' loss of income and inability to access financial support services during the pandemic resulted in many unable to pay rent or mortgage, and in need of assistance with basic needs items including food. Little is known about the unique experiences of sex workers who faced challenges in accessing food during the pandemic and its impact on healthcare access. Thus, we aimed to identify the association between pandemic-related challenges accessing food and primary healthcare among sex workers. METHODS: Prospective data were drawn from a cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers' Health Access, AESHA; 2010-present). Data were collected via questionnaires administered bi-annually from October 2020-August 2021. We used univariate and multivariable logistic regression with generalized estimating equations to assess the association between pandemic-related challenges accessing food and challenges accessing primary healthcare over the study period. RESULTS: Of 170 participants, 41% experienced pandemic-related challenges in accessing food and 26% reported challenges accessing healthcare. Median age was 45 years (IQR:36-53), 56% were of Indigenous ancestry, 86% experienced intimate partner violence in the last six months, and 62% reported non-injection substance use in the last six months. Experiencing pandemic-related challenges accessing food was positively associated with challenges accessing primary healthcare (Adjusted Odds Ratio: 1.99, 95% Confidence Interval: 1.02-3.88) after adjustment for confounders. CONCLUSIONS: Findings provide insight about the potential role community-based healthcare delivery settings (e.g., community clinics) can play in ameliorating access to basic needs such as food among those who are highly marginalized. Future pandemic response efforts should also take the most marginalized populations' needs into consideration by establishing strategies to ensure continuity of essential services providing food and other basic needs. Lastly, policies are needed establishing basic income support and improve access to food resources for marginalized women in times of crisis.

Housing Instability and Evictions Linked to Elevated Intimate Partner and Workplace Violence Among Women Sex Workers in Vancouver, Canada: Findings of a Prospective, Community-Based Cohort, 2010-2019.

Objectives. To model the relationship of unstable housing and evictions with physical and sexual violence perpetrated against women sex workers in intimate and workplace settings. Methods. We used bivariate and multivariable logistic regression with generalized estimating equations to model the association of unstable housing exposure and evictions with intimate partner violence (IPV) and workplace violence among a community-based longitudinal cohort of cisgender and transgender women sex workers in Vancouver, Canada, from 2010 through 2019. Results. Of 946 women, 85.9% experienced unstable housing, 11.1% eviction, 26.2% IPV, and 31.8% workplace violence. In multivariable generalized estimating equation models, recent exposure to unstable housing (adjusted odds ratio [AOR] = 2.04; 95% confidence interval [CI] = 1.45, 2.87) and evictions (AOR = 2.45; 95% CI = 0.99, 6.07) were associated with IPV, and exposure to unstable housing was associated with workplace violence (AOR = 1.46; 95% CI = 1.06, 2.00). Conclusions. Women sex workers face a high burden of unstable housing and evictions, which are linked to increased odds of intimate partner and workplace violence. Increased access to safe, women-centered, and nondiscriminatory housing is urgently needed. (Am J Public Health. 2023;113(4):442-452. https://doi.org/10.2105/AJPH.2022.307207).

Economic vulnerability, violence, and sexual risk factors for HIV among female sex workers in Tijuana, Mexico.

Economic vulnerability is often reported to underlie involvement in sex work among female sex workers (FSW), but may also create urgency in women's work, limiting women's negotiating power with clients and in turn, increasing their vulnerability for violence and HIV. This study assessed economic vulnerability in relation to violence and sexual risk behaviors for HIV among a sample of FSW in Tijuana, Mexico. FSW at least 18 years of age were recruited through venue-based sampling for a survey (n = 228) and in-depth interviews (n = 50) to investigate HIV risk factors in this region. Using crude and adjusted logistic regression models, we assessed lack of financial support from others as well as reports of financial hardship separately in relation to experiencing sexual violence (e.g. by clients, police, relationship partners, in the past 6 months), physical violence (past 6 months), STI diagnosis, and inconsistent condom use (past 30 days). Qualitative interviews (n = 50), conducted with a subsample of the survey participants, were also examined for related themes. FSW who reported no financial support were more likely to report sexual violence (OR = 2.1; 95% CI:1.1-4.2). FSW who reported financial hardship were more likely to experience sexual violence (OR = 1.9; 95% CI:1.1-3.6) and physical violence (OR = 1.9; 95% CI:1.1-3.6), as well as to report past 30-day inconsistent condom use (OR = 2.4; 95%CI: 1.3-4.6) and to test positive for an STI (OR = 1.9; 95% CI:1.1-3.4). Qualitative data substantiated these findings. Findings suggest that interventions to improve economic well-being may be useful to prevent the intersecting concerns of violence and HIV among FSW.

How cancer programs identify and address the financial burdens of rural cancer patients.

PURPOSE: Financial toxicity is associated with negative patient outcomes, and rural populations are disproportionately affected by the high costs of cancer care compared to urban populations. Our objective was to (1) understand cancer programs' perceptions of rural-urban differences in cancer patients' experiences of financial hardship, (2) evaluate the resources available to cancer patients across the rural-urban continuum, and (3) determine how rural and urban health care teams assess and address financial distress in cancer patients. METHODS: Seven research teams within the Cancer Prevention and Research Control Network conducted semi-structured interviews with cancer program staff who have a role in connecting cancer patients with financial assistance services in both rural and urban counties. Interviews were audio-recorded and transcribed. We identified themes using descriptive content and thematic analysis. RESULTS: We interviewed 35 staffs across 29 cancer care programs in seven states, with roughly half of respondents from programs in rural counties. Participants identified differences in rural and urban patients' experiences of financial hardship related to distance required to travel for treatment, underinsurance, and low socioeconomic status. Insufficient staffing was an identified barrier to addressing rural and urban patients' financial concerns. CONCLUSIONS: Improved financial navigation services could mitigate the effects of financial toxicity experienced by cancer patients, particularly rural patients, throughout treatment and survivorship. Future research is needed to improve how cancer programs assess financial hardship in patients and to expand financial navigation services to better serve rural cancer patients.

tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model.

tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the foetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5' tRNA halves from tRNAGly, tRNAGlu, tRNAVal and tRNALys are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 h after MIA and are suppressed thereafter. A group of 5' tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism.

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.

Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent.

Infection of the central nervous system (CNS) by murine polyomavirus (MuPyV), a persistent natural mouse pathogen, establishes brain-resident memory CD8 T cells (bTRM) that uniformly and chronically express programmed cell death protein 1 (PD-1) irrespective of the expression of αE integrin CD103, a TRM cell marker. In contrast, memory antiviral CD8 T cells in the spleen are PD-1-, despite viral loads being similar in both the brain and spleen during persistent infection. Repetitive antigen engagement is central to sustained PD-1 expression by T cells in chronic viral infections; however, recent evidence indicates that expression of inhibitory receptors, including PD-1, is part of the TRM differentiation program. Here we asked whether PD-1 expression by CD8 bTRM cells during persistent MuPyV encephalitis is antigen dependent. By transferring MuPyV-specific CD8 bTRM cells into the brains of naive mice and mice infected with cognate epitope-sufficient and -deficient MuPyVs, we demonstrate that antigen and inflammation are dispensable for PD-1 maintenance. In vitro and direct ex vivo analyses indicate that CD103- MuPyV-specific CD8 bTRM retain functional competence. We further show that the Pdcd-1 promoter of anti-MuPyV bTRM cells is epigenetically fixed in a demethylated state in the brain. In contrast, the PD-1 promoter of splenic antiviral memory CD8 T cells undergoes remethylation after being demethylated during acute infection. These data show that PD-1 expression is an intrinsic property of brain TRM cells in a persistent CNS viral infection.

Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner.

UNLABELLED: Mouse polyomavirus (MPyV) is a ubiquitous persistent natural mouse pathogen. A glutamic acid (E)-to-glycine (G) difference at position 91 of the VP1 capsid protein shifts the profile of tumors induced by MPyV from an epithelial to a mesenchymal cell origin. Here we asked if this tropism difference affects the MPyV-specific CD8 T cell response, which controls MPyV infection and tumorigenesis. Infection by the laboratory MPyV strain RA (VP1-91G) or a strain A2 mutant with an E-to-G substitution at VP1 residue 91 [A2(91G)] generated a markedly smaller virus-specific CD8 T cell response than that induced by A2(VP1-91E) infection. Mutant A2(91G)-infected mice showed a higher frequency of memory precursor (CD127(hi) KLRG1(lo)) CD8 T cells and a higher recall response than those of A2-infected mice. Using T cell receptor (TCR)-transgenic CD8 T cells and immunization with peptide-pulsed dendritic cells, we found that early bystander inflammation associated with A2 infection contributed to recruitment of the larger MPyV-specific CD8 T cell response. Beta interferon (IFN-ß) transcripts were induced early during A2 or A2(91G) infections. IFN-ß inhibited replication of A2 and A2(91G) in vitro Using mice lacking IFN-αß receptors (IFNAR(-/-)), we showed that type I IFNs played a role in controlling MPyV replication in vivo but differentially affected the magnitude and functionality of virus-specific CD8 T cells recruited by A2 and A2(91G) viral infections. These data indicate that type I IFNs are involved in protection against MPyV infection and that their effect on the antiviral CD8 T cell response depends on capsid-mediated tropism properties of the MPyV strain. IMPORTANCE: Isolates of the human polyomavirus JC virus from patients with the frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy (PML) carry single amino acid substitutions in the domain of the VP1 capsid protein that binds the sialic acid moiety of glycoprotein/glycolipid receptors on host cells. These VP1 mutations may alter neural cell tropism or enable escape from neutralizing antibodies. Changes in host cell tropism can affect recruitment of virus-specific CD8 T cells. Using mouse polyomavirus, we demonstrate that a single amino acid difference in VP1 known to shift viral tropism profoundly affects the quantity and quality of the anti-polyomavirus CD8 T cell response and its differentiation into memory cells. These findings raise the possibility that CD8 T cell responses to infections by human polyomaviruses may be influenced by VP1 mutations involving domains that engage host cell receptors.

Cutting Edge: Resident Memory CD8 T Cells Express High-Affinity TCRs.

Tissue-resident memory T (TRM) cells serve as vanguards of antimicrobial host defense in nonlymphoid tissues, particularly at barrier epithelia and in organs with nonrenewable cell types (e.g., brain). In this study, we asked whether an augmented ability to sense Ag complemented their role as early alarms of pathogen invasion. Using mouse polyomavirus, we show that brain-resident mouse polyomavirus-specific CD8 T cells, unlike memory cells in the spleen, progressively increase binding to MHC class I tetramers and CD8 coreceptor expression. Using the two-dimensional micropipette adhesion-frequency assay, we show that TRM cells in brain, as well as in kidney, express TCRs with up to 20-fold higher affinity than do splenic memory T cells, whereas effector cells express TCRs of similar high affinity in all organs. Together, these data demonstrate that TRM cells retain high TCR affinity, which endows them with the high Ag sensitivity needed for front-line defense against infectious agents.

High rate of burnout among anaesthesiologists in Belgrade teaching hospitals: Results of a cross-sectional survey.

BACKGROUND: Decisions by anaesthesiologists directly impact the treatment, safety, recovery and quality of life of patients. Physical or mental collapse due to overwork or stress (burnout) in anaesthesiologists may, therefore, be expected to negatively affect patients, departments, healthcare facilities and families. OBJECTIVES: To evaluate the prevalence of burnout among anaesthesiologists in Belgrade public teaching hospitals. DESIGN: A cross-sectional survey. SETTING: Anaesthesiologists in 10 Belgrade teaching hospitals. MAIN OUTCOME MEASURES: Burnout was assessed using Maslach Burnout Inventory-Human Services Survey. RESULTS: The response rate was 76.2% (205/272) with the majority of respondents women (70.7%). The prevalence of total burnout among anaesthesiologists in Belgrade teaching hospitals was 6.34%. Measured level of burnout as assessed by high emotional exhaustion, high depersonalisation and low personal accomplishment was 52.7, 12.2 and 28.8%, respectively. More than a quarter of the studied population responded in each category with symptoms of moderate burnout. We detected that sex, additional academic education, marital status and working conditions were risk factors for emotional exhaustion and depersonalisation. Ageing increased the likelihood of burnout by 21.3% with each additional year. Shorter professional experience and increased educational accomplishment increased the risk of total burnout by 272%. CONCLUSION: Burnout rates in Belgrade teaching hospitals among anaesthesiologists are higher than in foreign hospitals. Emotional and/or physical breakdowns can have serious effects when these individuals care for patients in extremely stressed situations that may occur perioperatively. Causes for burnout should be examined more closely and means implemented to reverse this process.

Preprocedural evaluation: considerations outside of the operating room.

PURPOSE OF REVIEW: There are an increasing number of procedures performed in locations outside of the operating room both for children and adults. From the perspective of the anesthesiologist, the preprocedural evaluation is essential in providing safe and high-quality care. This review focuses on the purpose, considerations and methods for providing information during the preprocedural evaluation process based on the most recent literature review. RECENT FINDINGS: Upon review of the literature, there is an agreement that a preprocedural evaluation is fundamental to the management of our patients. This evaluation is the process of clinical assessment that precedes the delivery of anesthesia for all procedures. Consideration must be given to information from many sources and consultation ordered only as necessary. A determination of the medical condition as indicated by the American Society of Anesthesiologists score must be applied. The evaluation process is relatively standard across institutions. It appears to be more clearly defined among adult patients particularly when presenting with multiple comorbidities, and will tend to be assessed days to weeks prior to the scheduled procedure. Differences may exist, however, among an institutions' overall approach to the preprocedural evaluation of children. Ultimately, the results are efforts by the institutions to improve efficiency, reduce delays and cancellation rates. SUMMARY: It is important for the anesthesia provider to perform a thorough preprocedural evaluation. Tests that are ordered as part of the evaluation are done to understand the current medical state, verify a condition or formulate a plan. Informed consent must be obtained and the risks and benefits of the anesthesia plan in a manner understandable to the patient and parent or care giver.Many pediatric patients undergoing procedures outside of the operating room are in good health, and their evaluation will be relatively routine. Other children will present with complex medical conditions that require more time for the evaluation process. This may include the consultation of a pediatric specialist(s) as a necessary step toward completion of the preprocedural evaluation.Similarly, there are adult patients undergoing procedures outside of the operating room, which will have a straightforward preprocedural evaluation and others are more complex. Disease states that might require further testing include diabetes, leukemia, kidney and liver disease, central nervous system disease, malabsorption syndrome, coronary artery disease, coagulopathies and patients on diuretics.

Interaction between dietary fat and exercise on excess postexercise oxygen consumption.

The objective of this study was to determine the effect of increased physical activity on subsequent sleeping energy expenditure (SEE) measured in a whole room calorimeter under differing levels of dietary fat. We hypothesized that increased physical activity would increase SEE. Six healthy young men participated in a randomized, single-blind, crossover study. Subjects repeated an 8-day protocol under four conditions separated by at least 7 days. During each condition, subjects consumed an isoenergetic diet consisting of 37% fat, 15% protein, and 48% carbohydrate for the first 4 days, and for the following 4 days SEE and energy balance were measured in a respiration chamber. The first chamber day served as a baseline measurement, and for the remaining 3 days diet and activity were randomly assigned as high-fat/exercise, high-fat/sedentary, low-fat/exercise, or low-fat/sedentary. Energy balance was not different between conditions. When the dietary fat was increased to 50%, SEE increased by 7.4% during exercise (P < 0.05) relative to being sedentary (baseline day), but SEE did not increase with exercise when fat was lowered to 20%. SEE did not change when dietary fat was manipulated under sedentary conditions. Physical activity causes an increase in SEE when dietary fat is high (50%) but not when dietary fat is low (20%). Dietary fat content influences the impact of postexercise-induced increases in SEE. This finding may help explain the conflicting data regarding the effect of exercise on energy expenditure.

CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion.

Repetitive Ag encounter, coupled with dynamic changes in Ag density and inflammation, imparts phenotypic and functional heterogeneity to memory virus-specific CD8 T cells in persistently infected hosts. For herpesvirus infections, which cycle between latency and reactivation, recent studies demonstrate that virus-specific T cell memory is predominantly derived from naive precursors recruited during acute infection. Whether functional memory T cells to viruses that persist in a nonlatent, low-level infectious state (smoldering infection) originate from acute infection-recruited naive T cells is not known. Using mouse polyomavirus (MPyV) infection, we previously showed that virus-specific CD8 T cells in persistently infected mice are stably maintained and functionally competent; however, a sizeable fraction of these memory T cells are short-lived. Further, we found that naive anti-MPyV CD8 T cells are primed de novo during persistent infection and contribute to maintenance of the virus-specific CD8 T cell population and its phenotypic heterogeneity. Using a new MPyV-specific TCR-transgenic system, we now demonstrate that virus-specific CD8 T cells recruited during persistent infection possess multicytokine effector function, have strong replication potential, express a phenotype profile indicative of authentic memory capability, and are stably maintained. In contrast, CD8 T cells recruited early in MPyV infection express phenotypic and functional attributes of clonal exhaustion, including attrition from the memory pool. These findings indicate that naive virus-specific CD8 T cells recruited during persistent infection contribute to preservation of functional memory against a smoldering viral infection.

Differential diagnosis of delayed awakening from general anesthesia: a review.

With the general use of fast acting anesthetic agents, patients usually awaken quickly in the post operative period. However, sometimes recovery is protracted and the list of possible causes in long. Accurate diagnosis is key to institution of appropriate therapy.

Hypotension on induction: anaphylaxis or cardiac failure?

Identification of the cause of hypotension after induction of anesthesia is critical as treatment differs. We describe a case of anaphylaxis in a patient with severe cardiac disease, diagnosed by echocardiography and successfully treated with immediate cardiovascular resuscitation, epinephrine, vasopressors and antihistamines.

Pollen products collected from honey bee hives experiencing minor stress have altered fungal communities and reduced antimicrobial properties.

Fungi are increasingly recognized to play diverse roles within honey bee hives, acting as pathogens, mutualists, and commensals. Pollen products, essential for hive nutrition, host significant fungal communities with potential protective and nutritional benefits. In this study, we profile the fungal communities and antifungal properties of three pollen products from healthy and stressed hives: fresh pollen collected by forager bees from local plants; stored pollen packed into the comb inside the hive; and bee bread, which is stored pollen following anaerobic fermentation used for bee and larval nutrition. Using amplicon sequencing, we found significant differences in fungal community composition, with hive health and sample type accounting for 8.8% and 19.3% of variation in beta diversity, respectively. Pollen and bee bread extracts had species-specific antimicrobial activity and inhibited the fungal hive pathogens Ascosphaera apis, Aspergillus flavus, and Aspergillus fumigatus, and the bacterial hive pathogen Paenibacillus larvae. Activity was positively correlated with phenolic and antioxidant content and was diminished in stressed hives. The plant source of pollen determined by amplicon sequencing differed in stressed hives, suggesting altered foraging behaviour. These findings illustrate the complex interplay between honey bees, fungal communities, and hive products, which should be considered in hive management and conservation.

Deletion of UL21 causes a delay in the early stages of the herpes simplex virus 1 replication cycle.

The herpes simplex virus 1 (HSV-1) U(L)21 gene encodes a 62-kDa tegument protein with homologs in the alpha-, beta-, and gammaherpesvirus subfamilies. In the present study, we characterized a novel U(L)21-null virus and its genetic repair to determine whether this protein plays a role in early stages of the HSV-1 replication cycle. Single-step growth analyses, protein synthesis time courses, and mRNA quantifications indicated that the absence of U(L)21 results in a delay early in the HSV-1 replication cycle.

Overcrowded housing reduces COVID-19 mitigation measures and lowers emotional health among San Diego refugees from September to November of 2020.

Refugee communities are vulnerable to housing insecurity, which drives numerous health disparity outcomes in a historically marginalized population. The COVID-19 pandemic has only worsened the ongoing affordable housing crisis in the United States while continuing to highlight disparities in health outcomes across populations. We conducted interviewer-administered surveys with refugee and asylum seekers in San Diego County at the height of the COVID-19 pandemic to understand the social effects and drivers of COVID-19 in one of the largest refugee communities in the United States. Staff from a community-based refugee advocacy and research organization administered the surveys from September-November 2020. 544 respondents participated in the survey, which captured the diversity of the San Diego refugee community including East African (38%), Middle Eastern (35%), Afghan (17%), and Southeast Asian (11%) participants. Nearly two-thirds of respondents (65%) reported living in overcrowded conditions (> 1 individual per room) and 30% in severely crowded conditions (> 1.5 individuals per room). For each additional person per room, self-reported poor emotional health increased. Conversely, family size was associated with a lower likelihood of reporting poor emotional health. Crowded housing was significantly associated with a lower probability of accessing a COVID-19 diagnostic test, with every additional reported person per room there was approximately an 11% increase in the probability of having never accessed a COVID-19 testing. Access to affordable housing had the largest effect size and was associated with fewer people per room. Overcrowding housing is a structural burden that reduces COVID-19 risk mitigation behaviors. Improved access to affordable housing units or receiving vouchers could reduce overcrowded housing in vulnerable refugee communities.