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The emergence of Japanese encephalitis virus (JEV) in eastern Australia in 2022 caused extensive reproductive disease in pigs and is a threat to public health. Groups of weaned piglets were experimentally infected with the Australian outbreak strain of JEV (genotype 4). All pigs challenged at 5 weeks of age were infected after an intradermal injection of 1 × 105.5 (n = 4) or 1 × 104.5 TCID50/pig (n = 5). Intranasal instillation was less effective at this age, infecting 3/4 pigs with the same higher dose and 1/5 with the lower dose. Intradermal injection using 1 × 105.0 TCID50/pig also infected 9/9 pigs at 11 weeks of age. Infection in all cases was confirmed by qRT-PCR of blood samples, which identified a viremia peak at 3–4 days and detected JEV-specific antibodies as early as 5 days after the challenge. The detection of JEV in oral and nasal swabs and in saliva from chew ropes was less consistent. JEV was detected in the tonsils of 21/22 infected pigs and was isolated from the tonsils of 9/9 pigs sampled 19 days after the challenge at 11 weeks of age. The infected pigs showed no clinical signs other than pyrexia on Days 4–6. Histopathology consistent with JEV infection was evident in the nervous tissues of all but two pigs sampled 28 days after the challenge and was characterized by meningitis, encephalitis and gliosis throughout the brain. Serological studies showed extensive cross-reactivity between JEV and Murray Valley encephalitis virus using blocking ELISAs. However, the determination of limiting-dilution titres allowed for the identification of the infecting virus. This in vivo infection model will be useful in evaluating JEV vaccines and for comparative pathogenesis studies with other JEV genotypes.

In a retrospective, cohort study at 4 medical centers with high coronavirus disease 2019 vaccination rates, we evaluated breakthrough severe acute respiratory syndrome coronavirus 2 Delta variant infections in vaccinated healthcare workers. Few work-related secondary cases were identified. Breakthrough cases were largely due to unmasked social activities outside of work.

BackgroundThe molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status.MethodsAnonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated.ResultsA total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively).ConclusionPatients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.

Engineering students face significant stressors such as high academic expectations and extreme time demands that have the potential to impact their mental health. Due to the mentoring responsibilities of chemical engineering faculty, faculty are often positioned to provide support for these students. Through this article, we aim to help prepare faculty to support student mental health, with guidance on identifying campus resources, navigating conversations with students in distress, and referring students to mental health services.

Purpose: Recent research on graduate students' diversity, equity and inclusion (DEI) socialization found that graduate colleges play a role in supporting graduate students' DEI professional development (Perez et al., 2020), but more studies are needed about how graduate colleges facilitate DEI socialization. One graduate college at a large, selective, research-intensive, public university in the Midwestern US created a graduate certificate for professional development in DEI to expand graduate students' capacities to contribute to inclusion and equity in higher education. The purpose of this multi-method program evaluation is to assess whether the certificate program created significant learning about DEI and developed intercultural competence among graduate students. Design/methodology/approach: The authors rely on multiple methods to evaluate the impact of the professional development DEI certificate. First, the authors used the Intercultural Development Inventory (IDI) pre and postassessment to measure the growth of participants in the first three years of the program. Second, the authors designed a reflection tool to assess significant learning after each component of the program. Finally, we conducted focus groups with graduates of the program to understand what program components were most valuable for DEI-related significant learning. Findings: The authors found that the DEI professional development program increased students' intercultural competence as measured by the IDI. Students reported perceptions of significant learning in every domain of learning we assessed using a self-reflection tool and in focus groups. Originality/value: To the best of the authors' knowledge, this is the first study that demonstrates how graduate colleges contribute to DEI socialization by preparing graduate students to interact across differences and contribute to inclusive climates both within and beyond academe.

BackgroundThe profound changes wrought by coronavirus disease 2019 (COVID-19) on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates.MethodsIn 148 HCA Healthcare-affiliated hospitals, from 1 March 2020 to 30 September 2020, and a subset of hospitals with microbiology and cluster data through 31 December 2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month.ResultsCentral line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% confidence interval [CI]: 23-108%) more CLABSI, 43% (95% CI: 8-90%) more CAUTI, and 44% (95% CI: 10-88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus, and Gram-negative organisms, were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased.ConclusionsCOVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

BackgroundSubstance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality.MethodsVeterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+). Outcomes were COVID-19+ by 11/01/20, hospitalization, ICU admission, or death within 60 days of a positive test. Main predictors were any ICD-10-CM SUDs, with substance-specific SUDs (cannabis, cocaine, opioid, stimulant, sedative) explored individually. Logistic regression produced unadjusted and covariate-adjusted odds ratios (OR; aOR).ResultsAmong COVID-19+ patients, 19.25% were hospitalized, 7.71% admitted to ICU, and 5.84% died. In unadjusted models, any SUD and all substance-specific SUDs except cannabis use disorder were associated with COVID-19+(ORs=1.06-1.85); adjusted models produced similar results. Any SUD and all substance-specific SUDs were associated with hospitalization (aORs: 1.24-1.91). Any SUD, cocaine and opioid disorder were associated with ICU admission in unadjusted but not adjusted models. Any SUD, cannabis, cocaine, and stimulant disorders were inversely associated with mortality in unadjusted models (OR=0.27-0.46). After adjustment, associations with mortality were no longer significant. In ad hoc analyses, adjusted odds of mortality were lower among the 49.9% of COVID-19+ patients with SUD who had SUD treatment in 2019, but not among those without such treatment.ConclusionsIn VHA patients, SUDs are associated with COVID-19 hospitalization but not COVID-19 mortality. SUD treatment may provide closer monitoring of care, ensuring that these patients received needed medical attention, enabling them to ultimately survive serious illness.

Gene replacement therapy is a rational therapeutic strategy and clinical intervention for neurodegenerative disorders like Canavan disease, a leukodystrophy caused by biallelic mutations in the aspartoacylase (ASPA) gene. We aimed to investigate whether simultaneous intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of rAAV9-CB6-ASPA provides a safe and effective therapeutic strategy in an open-label, individual-patient, expanded-access trial for Canavan disease. Immunomodulation was given prophylactically prior to adeno-associated virus (AAV) treatment to prevent an immune response to ASPA or the vector capsid. The patient served as his own control, and change from baseline was assessed by clinical pathology tests, vector genomes in the blood, antibodies against ASPA and AAV capsids, levels of cerebrospinal fluid (CSF) N-acetylaspartate (NAA), brain water content and morphology, clinical status, and motor function tests. Two years post treatment, the patient’s white matter myelination had increased, motor function was improved, and he remained free of typical severe epilepsy. NAA level was reduced at 3 months and remained stable up to 4 years post treatment. Immunomodulation prior to AAV exposure enables repeat dosing and has prevented an anti-transgene immune response. Dual-route administration of gene therapy may improve treatment outcomes.

AbstractChronic pain is associated with mental and physical health difficulties and is prevalent among veterans. Cannabis has been put forth as a treatment for chronic pain, and changes in laws, attitudes, and use patterns have occurred over the past 2 decades. Differences in prevalence of nonmedical cannabis use and cannabis use disorder (CUD) were examined across 2 groups: veterans or nonveterans and those reporting or not reporting recent pain. Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013; n = 36,309) were analyzed using logistic regression. Prevalence differences (PDs) for 3 cannabis outcomes (1) past-year nonmedical cannabis use, (2) frequent (≥3 times a week) nonmedical use, and (3) DSM-5 CUD were estimated for those reporting recent moderate to severe pain (veterans or nonveterans) and veterans reporting or not reporting recent pain. Difference in differences was calculated to investigate PDs on outcomes associated with residence in a state with medical cannabis laws (MCLs). Associations between physical and mental health and cannabis variables were tested. The results indicated that the prevalence of recent pain was greater among veterans (PD = 7.25%, 95% confidence interval (CI) [4.90-9.60]). Among veterans, the prevalence of frequent cannabis use was greater among those with pain (PD = 1.92%, 98% CI [0.21-3.63]), and among veterans residing in a state with MCLs, the prevalence of CUD was greater among those reporting recent pain (PD = 3.88%, 98% CI [0.36-7.39]). Findings failed to support the hypothesis that cannabis use improves mental or physical health for veterans with pain. Providers treating veterans with pain in MCL states should monitor such patients closely for CUD.

BackgroundImpairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (

ObjectiveThe Department of Veterans Affairs' (VA) electronic health records (EHR) offer a rich source of big data to study medical and health care questions, but patient eligibility and preferences may limit generalizability of findings. We therefore examined the representativeness of VA veterans by comparing veterans using VA healthcare services to those who do not.MethodsWe analyzed data on 3051 veteran participants age ≥ 18 years in the 2019 National Health Interview Survey. Weighted logistic regression was used to model participant characteristics, health conditions, pain, and self-reported health by past year VA healthcare use and generate predicted marginal prevalences, which were used to calculate Cohen's d of group differences in absolute risk by past-year VA healthcare use.ResultsAmong veterans, 30.4% had past-year VA healthcare use. Veterans with lower income and members of racial/ethnic minority groups were more likely to report past-year VA healthcare use. Health conditions overrepresented in past-year VA healthcare users included chronic medical conditions (80.6% vs. 69.4%, d = 0.36), pain (78.9% vs. 65.9%; d = 0.35), mental distress (11.6% vs. 5.9%; d = 0.47), anxiety (10.8% vs. 4.1%; d = 0.67), and fair/poor self-reported health (27.9% vs. 18.0%; d = 0.40).ConclusionsHeterogeneity in veteran sociodemographic and health characteristics was observed by past-year VA healthcare use. Researchers working with VA EHR data should consider how the patient selection process may relate to the exposures and outcomes under study. Statistical reweighting may be needed to generalize risk estimates from the VA EHR data to the overall veteran population.

Abstract Background At the outset of the COVID-19 pandemic, healthcare workers (HCWs) raised concerns about personal risks of acquiring infection during patient care. This led to more stringent infection prevention practices than CDC guidelines during a time of uncertainty about transmission and limited U.S. testing capacity. Hospitals were challenged to protect against true COVID-19 exposure risks, while avoiding use of unproven measures that could interfere with timely, high quality care. We evaluated hospital experiences with HCW COVID-19 exposure concerns impacting clinical workflow/management. Methods We conducted a 32-question structured survey of hospital infection prevention leaders (one per hospital) from CDC Prevention Epicenters, University of California (CA) Health system, HCA Healthcare, and the Southern CA Metrics Committee between May–Dec, 2020. We assessed facility characteristics and COVID-19 exposure concerns causing changes in respiratory care, procedure delays/modifications, requests to change infection prevention processes, disruptions in routine medical care, and health impacts of PPE overuse. Percentages were calculated among respondents for each question. Results Respondents represented 53 hospitals: 22 (42%) were small (< 200 beds), 14 (26%) medium (200-400 beds), and 17 (32%) large ( >400 beds) facilities. Of these, 11 (21%) provided Level 1 trauma care, and 22 (41%) provided highly immunocompromised patient care; 75% had cared for a substantial number of COVID-19 cases before survey completion. Majority reported changes in respiratory care delivery (71%-87%), procedural delays (75%-87%), requests to change infection prevention controls/protocols (58%-96%), and occupational health impacts of PPE overuse including skin irritation (98%) and carbon dioxide narcosis symptoms (55%) (Table). Conclusion HCW concerns over work-related COVID-19 exposure contributed to practice changes, many of which are unsupported by CDC guidance and resulted in healthcare delivery delays and alterations in clinical care. Pandemic planning and response must include the ability to rapidly develop evidence to guide infection prevention practice. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Deborah S. Yokoe, MD, MPH, Nothing to disclose Jonathan Grein, MD, Gilead (Other Financial or Material Support, Speakers fees) Stuart H. Cohen, MD, Seres (Research Grant or Support) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Abstract: Background: COVID-19 patients can remain positive by PCR-testing for several months. Pre-admission or pre-procedure testing can identify recovered asymptomatic patients who may no longer be contagious but would require precautions according to current CDC recommendations (10 days). This can result in unintended consequences, including procedure delays or transfer to appropriate care (e.g., psychiatric or post-trauma patients requiring admission to COVID-19 units instead of psychiatric or rehabilitation facilities, respectively). Methods: We conducted a structured survey of healthcare epidemiologists and infection prevention experts from the SHEA Research Network between March-April, 2021. The 14-question survey, presented a series of COVID-19 PCR+ asymptomatic patient case scenarios and asked respondents if (1) they would consider the case recovered and not infectious, (2) if they have cleared precautions in such cases, and if so, (3) how many transmission events occurred after discontinuing precautions. The survey used one or a combination of 5 criteria: history of COVID-19 symptoms, history of exposure to a household member with COVID-19, COVID-19 PCR cycle threshold (CT), and IgG serology. Percentages were calculated among respondents for each question. Results: Among 60 respondents, 56 (93%) were physicians, 51 (86%) were hospital epidemiologists, and 46 (77%) had >10y infection prevention experience. They represented facilities that cumulatively cared for >29,000 COVID-19 cases; 46 (77%) were academic, and 42 (69%) were large ( >400 beds). One-third to one-half would consider an incidentally found PCR+ case as recovered based on solo criteria, particularly those with two consecutive high CTs or COVID IgG positivity recovered (53-55%) (Table 1). When combining two criteria, half to four-fifths of respondents deemed PCR+ cases to be recovered (Table 2). Half of those had used those criteria to clear precautions (45-64%) and few to none experienced a subsequent transmission event resulting from clearance. Conclusion: The majority of healthcare epidemiologists consider a combination of clinical and diagnostic criteria as recovered and many have used these to clear precautions without high numbers of transmission. Disclosures: Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Deborah S. Yokoe, MD, MPH, Nothing to disclose Stuart H. Cohen, MD, Seres (Research Grant or Support) Jonathan Grein, MD, Gilead (Other Financial or Material Support, Speakers fees) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Abstract Background The profound changes wrought by COVID-19 on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). Objective Evaluate the association between COVID-19 surges and HAI or cluster rates Methods Design: Prospective cohort study Setting 148 HCA Healthcare-affiliated hospitals, 3/1/2020-9/30/2020, and a subset of hospitals with microbiology and cluster data through 12/31/2020 Patients All inpatients Measurements We evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month at each hospital. Results Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased (P ≤ 0.001 for all), with 60% (95% CI, 23 to 108%) more CLABSI, 43% (95% CI, 8 to 90%) more CAUTI, and 44% (95% CI, 10 to 88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection (CDI) was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus and Gram-negative organisms were each significantly associated with COVID-19 surges (P < 0.05 for all). Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased (P = 0.02). Limitations Variations in surveillance and reporting may affect HAI data. Table 1. Effect of an increase in number of COVID-19 discharges on HAIs and hospital-onset pathogens Figure 1. Predicted mean HAI rates as COVID-19 discharges increase Predicted mean HAI rate by increasing monthly COVID-19 discharges. Panel a. CLABSI, Panel b, CAUTI Panel c. MRSA Bacteremia, Panel d. CDI. Data are stratified by small, medium and large hospitals. Figure 2. Monthly comparison of COVID discharges to clusters COVID-19 discharges and the number of clusters of hospital-onset pathogens are correlated throughout the pandemic. Conclusion COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention. Disclosures Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Micaela H. Coady, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Deborah S. Yokoe, MD, MPH, Nothing to disclose Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)

A retrospective cohort study at four academic medical centers with high COVID-19 vaccination rates evaluated breakthrough SARS-CoV-2 Delta variant (B.1.617.2) infections in vaccinated healthcare workers. Few work-related secondary cases were identified. Breakthrough cases were largely due to unmasked social activities outside of work.

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

The improper disposal of PET bottle waste in Brazil jeopardizes the sustainability goals, impacting the social, economic, and environmental aspects. In order to tackle this issue, this study introduces a framework that was developed using a combination of environmental and social life cycle assessments (LCAs), along with a modified Analytic Hierarchy Process (AHP) methodology. Nine disposal scenarios were evaluated in Bauru, Brazil, including various combinations of landfills, sorting cooperatives, and incineration. Environmental (Env-LCA) and social (S-LCA) assessments followed the ISO 14040 standards, with the S-LCA incorporating the UNEP/SETAC guidelines. Scenario 9 was identified as the most sustainable option from the evaluated scenarios, with 100% of the waste sent to sorting cooperatives, with modified collection schemes. Conversely, Scenario 1, with a high landfill percentage, proved to be the least sustainable.

Abstract Background Reasons underlying disparities in telehealth use among cancer survivors are unknown. Methods We surveyed a sociodemographically diverse population‐based cohort of 487 prostate cancer survivors regarding their use and perceptions of telehealth during the COVID‐19 pandemic. Results Overall, only 28.5% of survivors had used telehealth at the time of survey and just 10% felt care through telehealth is comparable to that of an in‐person visit. Still, over 55% felt telehealth is a good option for initial consultations or basic care and 15% felt more likely to use telehealth since the pandemic. After adjusting for other socioeconomic factors, survivors with lower education (≤high school vs. any college) had marginally lower use of telehealth (risk ratio [RR], 0.65 [95% CI, 0.42–1.01]) and lower probability of feeling more likely to use telehealth since the pandemic (RR, 0.39 [95% CI, 0.20–0.77]). Conclusions Differences in survivor perceptions of telehealth by education level highlight new insights underlying disparities in telehealth use and potential targets for interventions.

Abstract Objectives The glucocorticoid receptor (GR) is a well-studied, ligand-activated transcription factor and a common target of anti-inflammatory treatments. Recently, several studies have drawn attention the effects of binding of GR to RNA rather than DNA and the potential implications of this activity for GR function. The objective of our study was to further characterize the relationship between GR function and RNA binding by measuring changes in the glucocorticoid-driven transcriptome in the presence of a GR mutant that exhibited reduced RNA affinity. Data description GR was activated in three cell lines containing GR constructs (GR-HaloTag). One of the cell lines contained a wild-type GR-HaloTag. Another contained GR-HaloTag with a mutation that reduced RNA affinity and slightly reduced DNA affinity. The third cell line contained GR-HaloTag with a mutation that only slightly reduced DNA affinity. All three cell lines were treated with dexamethasone, a GR agonist. RNA-seq samples were collected every hour for 3 h. Moreover, transcriptome quantification was accomplished via labeling of RNAs transcribed in the final hour of dexamethasone treatment using 4-thiouridine. These labeled RNAs were then purified and sequenced. This data set is the first of its kind for GR and contains valuable insights into the function of RNA binding by GR.

Abstract The glucocorticoid receptor (GR) is a ligand-activated transcription factor that regulates a suite of genes through direct binding of GR to specific DNA promoter elements. GR also interacts with RNA, but the function of this RNA-binding activity remains elusive. Current models speculate that RNA could repress the transcriptional activity of GR. To investigate the function of the GR-RNA interaction on GR’s transcriptional activity, we generated cells that stably express a mutant of GR with reduced RNA binding affinity and treated the cells with the GR agonist dexamethasone. Changes in the dexamethasone-driven transcriptome were quantified using 4-thiouridine labeling of RNAs followed by high-throughput sequencing. We find that while many genes are unaffected, GR-RNA binding is repressive for specific subsets of genes in both dexamethasone-dependent and independent contexts. Genes that are dexamethasone-dependent are activated directly by chromatin-bound GR, suggesting a competition-based repression mechanism in which increasing local concentrations of RNA may compete with DNA for binding to GR at sites of transcription. Unexpectedly, genes that are dexamethasone-independent instead display a localization to specific chromosomal regions, which points to changes in chromatin accessibility or architecture. These results show that RNA binding plays a fundamental role in regulating GR function and highlights potential functions for transcription factor-RNA interactions.

Congenital anomalies in Sub-Sahara Africa (SSA) are understudied despite the significant pediatric health burden. This retrospective longitudinal hospital-based study evaluated the records of 326 inpatient children under the age of two years with congenital anomalies at Bugando Medical Centre, a tertiary referral hospital in northwestern Tanzania. Classical logistic regression was used in the analysis of congenital malformation of muscles, gastrointestinal malformation, oral facial clefts, neural tube defects, and skeletal malformations. A modified poisson regression was used to model risk factors for Central Nervous System (CNS) hydrocephalus and congenital heart disease (CHD). A majority (78.8%) of children included in the study were less than six months of age. Nearly half (48.8%) were diagnosed with CHD followed by CNS hydrocephalus (10.4%) and congenital malformation of muscles (8.9%). Babies whose mothers missed periconceptual folic acid supplementation had 83% higher risk of hydrocephalus (aPR = 1.83, 95% CI = 1.11-1.96) and 78% higher for CHD (aPR = 1.78, 95% CI = 1.31-1.94). Male children had 1.67 higher odds of muscular congenital malformations (aOR = 1.67, 95% CI = 1.23-1.89). Less than 37 gestational age had a 1.86 higher odds of muscular congenital malformations (aOR = 1.86, 95% CI = 1.53-3.66). Our study highlights the critical need for folic acid supplementation and establishes a need for a registry and the potential for mapping.