ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.

The SARS-CoV-2 virus emerged in December 2019 and has caused a worldwide pandemic due to the lack of any pre-existing immunity. Accurate serology testing is urgently needed to help diagnose infection, determine past exposure of populations and assess the response to a future vaccine. The landscape of antibody responses to SARS-CoV-2 is unknown. In this study, we utilized the luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19. We identified new targets of the immune response to SARS-CoV-2 and show that nucleocapsid, open reading frame (ORF)8 and ORF3b elicit the strongest specific antibody responses. ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity. Our findings could be used to develop second-generation diagnostic tests to improve serological assays for COVID-19 and are important in understanding pathogenicity.

Author Correction: ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Infection of dogs with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19)1,2. In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog3. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Here, using PCR with reverse transcription, serology, sequencing the viral genome and virus isolation, we show that 2 out of 15 dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected with SARS-CoV-2. SARS-CoV-2 RNA was detected in five nasal swabs collected over a 13-day period from a 17-year-old neutered male Pomeranian. A 2.5-year-old male German shepherd was positive for SARS-CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Antibody responses were detected in both dogs using plaque-reduction-neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The dogs remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans.

Diffusion and distal linkages govern interchromosomal dynamics during meiotic prophase.

SignificanceEssential for sexual reproduction, meiosis is a specialized cell division required for the production of haploid gametes. Critical to this process are the pairing, recombination, and segregation of homologous chromosomes (homologs). While pairing and recombination are linked, it is not known how many linkages are sufficient to hold homologs in proximity. Here, we reveal that random diffusion and the placement of a small number of linkages are sufficient to establish the apparent "pairing" of homologs. We also show that colocalization between any two loci is more dynamic than anticipated. Our study provides observations of live interchromosomal dynamics during meiosis and illustrates the power of combining single-cell measurements with theoretical polymer modeling.

SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms.

The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 (SOX9) and SOX10 (SOXE) transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia SOX9Y440X mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that SOX9Y440X causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous Sox9-null mice are normal. During the ES development of Sox9Y440X/+ heterozygotes, Sox10 and genes important for ionic homeostasis are down-regulated, and there is developmental persistence of progenitors, resulting in fewer mature cells. Sox10 heterozygous null mutants also display persistence of ES/duct progenitors. By contrast, SOX10 retains its expression in the early Sox9Y440X/+ mutant cochlea. Later, in the postnatal stria vascularis, dominant interference by SOX9Y440X is implicated in impairing the normal cooperation of SOX9 and SOX10 in repressing the expression of the water channel Aquaporin 3, thereby contributing to endolymphatic hydrops. Our study shows that for a functioning endolymphatic system in the inner ear, SOX9 regulates Sox10, and depending on the cell type and target gene, it works either independently of or cooperatively with SOX10. SOX9Y440X can interfere with the activity of both SOXE factors, exerting effects that can be classified as haploinsufficient/hypomorphic or dominant negative depending on the cell/gene context. This model of disruption of transcription factor partnerships may be applicable to congenital deafness, which affects ∼0.3% of newborns, and other syndromic disorders.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Amino acid substitution L232F in non-structural protein 6 identified as a possible human-adaptive mutation in clade B MERS coronaviruses.

IMPORTANCE: Viral host adaptation plays an important role in inter-species transmission of coronaviruses and influenza viruses. Multiple human-adaptive mutations have been identified in influenza viruses but not so far in MERS-CoV that circulates widely in dromedary camels in the Arabian Peninsula leading to zoonotic transmission. Here, we analyzed clade B MERS-CoV sequences and identified an amino acid substitution L232F in nsp6 that repeatedly occurs in human MERS-CoV. Using a loss-of-function reverse genetics approach, we found the nsp6 L232F conferred increased viral replication competence in vitro, in cultures of the upper human respiratory tract ex vivo, and in lungs of mice infected in vivo. Our results showed that nsp6 L232F may be an adaptive mutation associated with zoonotic transmission of MERS-CoV. This study highlighted the capacity of MERS-CoV to adapt to transmission to humans and also the need for continued surveillance of MERS-CoV in camels.

Understanding the Impact of Enhanced Recovery Programs on Social Vulnerability, Race, and Colorectal Surgery Outcomes.

BACKGROUND: Increasing social vulnerability, measured by the Social Vulnerability Index, has been associated with worse surgical outcomes. However, less is known about the impact of social vulnerability on patients who underwent colorectal surgery under enhanced recovery programs. OBJECTIVE: We hypothesized that increasing social vulnerability is associated with worse outcomes before enhanced recovery implementation, but that after implementation, disparities in outcomes would be reduced. DESIGN: Retrospective cohort study using multivariable logistic regression to identify associations of social vulnerability and enhanced recovery with outcomes. SETTINGS: Institutional American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing elective colorectal surgery (2010-2020). Enhanced recovery programs were implemented in 2015. Those adhering to 70% or more of enhanced recovery program components were defined as enhanced recovery and all others as nonenhanced recovery. OUTCOMES: Length of stay, complications, and readmissions. RESULTS: Of 1523 patients, 589 (38.7%) were in the enhanced recovery group, with 625 patients (41%) in the lowest third of the Social Vulnerability Index, 411 (27%) in the highest third. There were no differences in Social Vulnerability Index distribution by the enhanced recovery group. On multivariable modeling, social vulnerability was not associated with increased length of stay, complications, or readmissions in the enhanced recovery group. Black race was associated with increased length of stay in both the nonenhanced recovery (OR 1.2; 95% CI, 1.1-1.3) and enhanced recovery groups (OR 1.2; 95% CI, 1.1-1.4). Enhanced recovery adherence was associated with reductions in racial disparities in complications as the Black race was associated with increased odds of complications in the nonenhanced recovery group (OR 1.9; 95% CI, 1.2-3.0) but not in the enhanced recovery group (OR 0.8; 95% CI, 0.4-1.6). LIMITATIONS: Details of potential factors affecting enhanced recovery program adherence were not assessed and are the subject of current work by this team. CONCLUSION: High social vulnerability was not associated with worse outcomes among both enhanced recovery and nonenhanced recovery colorectal patients. Enhanced recovery program adherence was associated with reductions in racial disparities in complication rates. However, disparities in length of stay remain, and work is needed to understand the underlying mechanisms driving these disparities. See Video Abstract . COMPRENDIENDO EL IMPACTO DE LOS PROGRAMAS DE RECUPERACIN MEJORADA EN LA VULNERABILIDAD SOCIAL, LA RAZA Y LOS RESULTADOS DE LA CIRUGA COLORRECTAL: ANTECEDENTES:El aumento de la vulnerabilidad social medida por el índice de vulnerabilidad social se ha asociado con peores resultados quirúrgicos. Sin embargo, se sabe menos sobre el impacto de la vulnerabilidad social en los pacientes de cirugía colorrectal bajo programas de recuperación mejorados.OBJETIVO:Planteamos la hipótesis de que el aumento de la vulnerabilidad social se asocia con peores resultados antes de la implementación de la recuperación mejorada, pero después de la implementación, las disparidades en los resultados se reducirían.DISEÑO:Estudio de cohorte retrospectivo que utilizó regresión logística multivariable para identificar asociaciones de vulnerabilidad social y recuperación mejorada con los resultados.ESCENARIO:Base de datos institucional del Programa de Mejora Nacional de la Calidad de la Cirugía del American College of Surgeons.PACIENTES:Pacientes sometidos a cirugía colorrectal electiva (2010-2020). Programas de recuperación mejorada implementados en 2015. Aquellos que se adhieren a ≥70% de los componentes del programa de recuperación mejorada definidos como recuperación mejorada y todos los demás como recuperación no mejorada.MEDIDAS DE RESULTADO:Duración de la estancia hospitalaria, complicaciones y reingresos.RESULTADOS:De 1.523 pacientes, 589 (38,7%) estaban en el grupo de recuperación mejorada, con 732 (40,3%) pacientes en el tercio más bajo del índice de vulnerabilidad social, 498 (27,4%) en el tercio más alto, y no hubo diferencias en la distribución del índice vulnerabilidad social por grupo de recuperación mejorada. En el modelo multivariable, la vulnerabilidad social no se asoció con una mayor duración de la estancia hospitalaria, complicaciones o reingresos en ninguno de los grupos de recuperación mejorada. La raza negra se asoció con una mayor duración de la estadía tanto en el grupo de recuperación no mejorada (OR1,2, IC95% 1,1-1,3) como en el grupo de recuperación mejorada (OR1,2, IC95% 1,1-1,4). La adherencia a la recuperación mejorada se asoció con reducciones en las disparidades raciales en las complicaciones, ya que la raza negra se asoció con mayores probabilidades de complicaciones en el grupo de recuperación no mejorada (OR1,9, IC95% 1,2-3,0), pero no en el grupo de recuperación mejorada (OR0,8, IC95% 0,4-1,6).LIMITACIONES:No se evaluaron los detalles de los factores potenciales que afectan la adherencia al programa de recuperación mejorada y son el tema del trabajo actual de este equipo.CONCLUSIÓN:La alta vulnerabilidad social no se asoció con peores resultados entre los pacientes colorrectales con recuperación mejorada y sin recuperación mejorada. Una mayor adherencia al programa de recuperación se asoció con reducciones en las disparidades raciales en las tasas de complicaciones. Sin embargo, persisten disparidades en la duración de la estadía y es necesario trabajar para comprender los mecanismos subyacentes que impulsan estas disparidades. (Traducción-Dr. Felipe Bellolio ).

Racial Disparity in Length of Stay Following Implementation of a Bariatric Enhanced Recovery Program.

INTRODUCTION: Enhanced Recovery Programs (ERPs) mitigate racial disparities in postoperative length of stay (LOS) for colorectal populations. It is unclear, however, if these effects exist in the bariatric surgery population. Therefore, this study aimed to evaluate the racial disparities in LOS before and after implementation of bariatric surgery ERP. METHODS: A retrospective cohort study was performed using data from a single institution. Patients undergoing minimally invasive sleeve gastrectomy or Roux-en-Y gastric bypass from 2017 to 2019 (pre-ERP) or 2020-2022 (ERP) were included. Chi-square, Kruskal-Wallis, and analysis of variance were used to compare groups, and estimated LOS (eLOS) was assessed via multivariable regression. RESULTS: Seven hundred sixty four patients were identified, including 363 pre-ERPs and 401 ERPs. Pre-ERP and ERP cohorts were similar in age (median 44.3 years versus 43.8 years, P = 0.80), race (53.4% Black versus 56.4% Black, P = 0.42), and preoperative body mass index (median 48.3 versus 49.4, P = 0.14). Overall median LOS following bariatric surgery decreased from 2 days pre-ERP to 1 day following ERP (P < 0.001). Average LOS for Black and White patients decreased by 0.5 and 0.48 days, respectively. However, overall eLOS remained greater for Black patients compared with White patients despite ERP implementation (eLOS 0.21 days, P = 0.01). CONCLUSIONS: Implementation of a bariatric surgery ERP was associated with decreased LOS for both Black and White patients. However, Black patients did have slightly longer LOS than White patients in both pre-ERP and ERP eras. More work is needed to understand the driving mechanism(s) of these disparities to eliminate them.

Uncommon Sociodemographic Factors Are Associated With Racial Disparities in Length of Stay Following Oncologic Elective Colectomy.

INTRODUCTION: Although outcome disparities by race have been identified in colorectal cancer, these patterns are challenging to explain using variables that are commonly available in databases. In a single institution serving a diverse community, length of stay (LOS) varies by race following elective oncologic colectomy. We investigated previously unexplored variables that may explain the relationship between race and LOS following elective resection of colorectal neoplasms. METHODS: Retrospective, single institution cohort study from January 2015 to December 2020 for adult patients undergoing elective colorectal cancer resections. Baseline demographic variables and intraoperative factors were analyzed for changes in LOS following elective colorectal resection. Additional retrospective chart review was carried out to determine household member composition and distance from home to hospital. Bivariate analysis was conducted to determine which variables should be included in multivariable analyses. All analyses were conducted using SAS Academic. RESULTS: Most patients (n = 383) were Asian (40%), Black (12%), or Hispanic (26%). Race and LOS were associated with age (P = 0.001 and P < 0.001 for race and LOS, respectively), American Society of Anesthesiologists class (P = 0.004 and P < 0.001), enhanced recovery after surgery protocols (P = 0.006 and P < 0.001), household members (P = 0.009 and P = 0.002), and discharge disposition (P = 0.049 and P < 0.001). In multivariable analysis, household members (P = 0.021) independently remained associated with LOS after controlling for race (P = 0.008) and discharge disposition (P < 0.001). CONCLUSIONS: Household member composition varies with LOS, suggesting that level of support at home may influence decisions regarding discharge disposition, which lead to differences in LOS.

Sexual risk characteristics, social vulnerability, and anal cancer screening uptake among men living with HIV in the deep south.

ABSTRACTWithout standard guidelines, there is a critical need to examine anal cancer screening uptake in the South which has the highest HIV incidence in the U.S. We identified factors associated with screening among men living with HIV (MLHIV) at a large academic HIV outpatient clinic in Alabama. Relationships between sociodemographic, clinical, sexual risk characteristics and screening were examined using T-tests, Fisher's exact, Chi-square, and logistic regression analyses. Unadjusted and adjusted odds ratios (AOR) were computed to estimate the odds of screening. Among 1,114 men, 52% had received annual anal cytology (pap) screening. Men who were screened were more likely to have multiple sexual partners compared to men who were not screened (22.8% vs. 14.8%, p = 0.002). Among men with one partner, the youngest were almost five times more likely to be screened compared to middle-aged men (AOR = 4.93, 95% CI: 2.34-10.39). Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Our findings suggest a racial disparity, with older black MLHIV being the least likely to be screened. In the South, MLHIV who are older, black, heterosexual, or live in high social vulnerability counties may be less likely to receive annual anal cancer screening.

Decreased risk of non-influenza respiratory infection after influenza B virus infection in children.

Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009-2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27-0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.

Multi-shell connectome DWI-based graph theory measures for the prediction of temporal lobe epilepsy and cognition.

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome that empirically represents a network disorder, which makes graph theory (GT) a practical approach to understand it. Multi-shell diffusion-weighted imaging (DWI) was obtained from 89 TLE and 50 controls. GT measures extracted from harmonized DWI matrices were used as factors in a support vector machine (SVM) analysis to discriminate between groups, and in a k-means algorithm to find intrinsic structural phenotypes within TLE. SVM was able to predict group membership (mean accuracy = 0.70, area under the curve (AUC) = 0.747, Brier score (BS) = 0.264) using 10-fold cross-validation. In addition, k-means clustering identified 2 TLE clusters: 1 similar to controls, and 1 dissimilar. Clusters were significantly different in their distribution of cognitive phenotypes, with the Dissimilar cluster containing the majority of TLE with cognitive impairment (χ2 = 6.641, P = 0.036). In addition, cluster membership showed significant correlations between GT measures and clinical variables. Given that SVM classification seemed driven by the Dissimilar cluster, SVM analysis was repeated to classify Dissimilar versus Similar + Controls with a mean accuracy of 0.91 (AUC = 0.957, BS = 0.189). Altogether, the pattern of results shows that GT measures based on connectome DWI could be significant factors in the search for clinical and neurobehavioral biomarkers in TLE.

What Is Health Literacy Among Orthognathic Surgery Patients?

BACKGROUND: Health literacy of orthognathic surgery patients has not been thoroughly evaluated. PURPOSE: The purpose of this study was to estimate health literacy and identify risk factors associated with inadequate health literacy in orthognathic surgery patients. STUDY DESIGN, SETTING, SAMPLE: A cross-sectional study was implemented utilizing patients ages 14-80 years who presented for orthognathic surgery evaluation between September 2021 and December 2022. Subjects were excluded from the study if they did not complete the orthognathic surgery evaluation, were not between the ages of 14-80 years old, or did not complete the Brief Health Literacy Screening Tool (BRIEF) questionnaire during intake. Subjects who have not undergone orthognathic surgery but completed the initial evaluation for orthognathic surgery were included in the study. PREDICTOR VARIABLES: The predictor variables were a set of risk factors for inadequate health literacy: age, sex, primary language, race, estimated household income, and diagnosis. MAIN OUTCOME VARIABLE: The main outcome variable was health literacy assessed using the BRIEF questionnaire. During intake, subjects completed the BRIEF questionnaire consisting of four questions scored on an ordinal scale of 1-5. Inadequate health literacy was defined as a BRIEF score ≤16. COVARIATES: Not applicable. ANALYSES: Bivariate and multivariate analyses were performed. P < .05 was considered statistically significant. RESULTS: Of 150 patients presenting for orthognathic surgery, fifteen percent of patients had inadequate health literacy via the BRIEF test. The mean age of those with adequate health literacy was 27.9 years (standard deviation, ±12.5) compared to 18.5 years (standard deviation, ±5.7) for those with inadequate health literacy (P = <.001). After adjusting for sex, language, race, estimated household income, and diagnosis via multivariate analysis, increasing age was associated with decreased odds of inadequate health literacy (adjusted odds ratio = 0.81; confidence interval, 0.72-0.92; P = <.001). CONCLUSION AND RELEVANCE: In the complex process of orthognathic surgery, it is essential to identify patients with inadequate health literacy that may require additional health literacy interventions. Ultimately, 15% of orthognathic surgery subjects had inadequate health literacy, and younger patients were the most susceptible as the odds of inadequate health literacy decreased with increasing age.

Rad21l1 cohesin subunit is dispensable for spermatogenesis but not oogenesis in zebrafish.

During meiosis I, ring-shaped cohesin complexes play important roles in aiding the proper segregation of homologous chromosomes. RAD21L is a meiosis-specific vertebrate cohesin that is required for spermatogenesis in mice but is dispensable for oogenesis in young animals. The role of this cohesin in other vertebrate models has not been explored. Here, we tested if the zebrafish homolog Rad21l1 is required for meiotic chromosome dynamics during spermatogenesis and oogenesis. We found that Rad21l1 localizes to unsynapsed chromosome axes. It is also found between the axes of the mature tripartite synaptonemal complex (SC) in both sexes. We knocked out rad21l1 and found that nearly all rad21l1-/- mutants develop as fertile males, suggesting that the mutation causes a defect in juvenile oogenesis, since insufficient oocyte production triggers female to male sex reversal in zebrafish. Sex reversal was partially suppressed by mutation of the checkpoint gene tp53, suggesting that the rad21l1 mutation activates Tp53-mediated apoptosis or arrest in females. This response, however, is not linked to a defect in repairing Spo11-induced double-strand breaks since deletion of spo11 does not suppress the sex reversal phenotype. Compared to tp53 single mutant controls, rad21l1-/- tp53-/- double mutant females produce poor quality eggs that often die or develop into malformed embryos. Overall, these results indicate that the absence of rad21l1-/- females is due to a checkpoint-mediated response and highlight a role for a meiotic-specific cohesin subunit in oogenesis but not spermatogenesis.

Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential.

Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV-infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.

Disparities in Perioperative Use of Patient Engagement Technologies - Not All Use is Equal.

OBJECTIVE: To determine the association of patient-level characteristics on the use of a patient engagement technology during the perioperative period. SUMMARY OF BACKGROUND DATA: As implementation of patient engagement technologies continues to grow, it remains unclear who uses, and not uses, these technologies. Existing literature suggests significant disparities in usage of other technologies by patient age, race, sex, and geographic location, however, have yet to characterize patient usage of patient engagement technologies. METHODS: This is a retrospective cohort study of patients undergoing elective surgery by a colorectal surgeon between January 2018 and March 2020 who enrolled in a patient engagement technology at a single institution. Patients enrolled received educational content, healthcare reminders, patient reported outcome (PRO) surveys, and health checks preoperatively, in-hospital, and for 30-days postdischarge. The primary outcome was patient activation of the patient engagement technology. Secondary outcomes were completion of at least 1 PRO survey, 1 in-hospital health check, and 1 postdischarge health check. RESULTS: Of 549 patients who enrolled in the patient engagement technology, 473 (86.2%) activated. On multivariable stepwise regression, female patients [odds ratio (OR) 2.4, confidence interval (CI) 1.4-4.0, P = 0.001] and privately insured patients (OR 2.0, CI 1.1-3.8, P = 0.03) were more likely to activate. Black patients were less likely to activate (OR 0.5, CI 0.3-0.9, P = 0.02). Once activated, privately insured patients were more likely to complete PRO surveys (OR 2.3, CI 1.2-4.3, P = 0.01), in-hospital health checks (OR 2.4, CI 1.4-4.1, P = 0.002), and postdischarge health checks (OR 1.9, CI 1.1 -3.3, P < 0.001) than uninsured patients. Black patients were less likely to complete PRO surveys (OR 0.4, CI 0.3-0.7, P = 0.001) and in-hospital health checks (OR 0.6, CI 0.4-0.9, P = 0.03) than White patients. CONCLUSIONS: Use of a patient engagement technology in the perioperative period differs significantly by sex, race/ethnicity, and insurance status. These technologies may not be used equally by all patients, which should be considered during implementation of interventions to improve surgical outcomes.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

OBJECTIVE: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. METHODS: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. RESULTS: Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. SIGNIFICANCE: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

Use of a mobile health patient engagement technology improves perioperative outcomes in gynecologic oncology patients.

OBJECTIVE: To evaluate the impact of a mobile health patient engagement technology (PET) on postoperative outcomes in gynecologic oncology patients. METHODS: All gynecologic oncology patients undergoing laparotomy on an enhanced recovery program (ERP) were approached from July 2019 to May 2021 to enroll in a PET, which can be accessed by computer, tablet, or smart phone. This platform provides enhanced pre- and postoperative patient education and remote patient monitoring. Patients who elected to participate were provided with targeted education based on their age and comorbidities and were asked to complete daily health checks during the postoperative period. Participants in the PET were compared to patients who opted out as well as to a historical cohort from prior to PET implementation. Patient and procedure-level factors were recorded. The primary outcomes were length of stay (LOS) and 30-day readmission rate. Analysis was performed using SPSS v.26. RESULTS: 682 women met inclusion criteria during the study time; 347 in the PET group and 335 in the control group. Demographic and other factors including race, BMI (kg/m2), Charlson Comorbidity Index (CCI), surgical complexity, and insurance status were not different between the PET and control group; however, patients in the PET cohort were slightly younger (55.0 yo vs. 57.2 yo; p = 0.04). Patients in the PET group had a significantly shorter LOS (2.9 days vs. 3.6 days; p < 0.01) and lower readmission rate (4.3% vs. 8.6%; p < 0.01) when compared with the control group. CONCLUSIONS: Use of a PET in our gynecologic oncology patients decreased LOS by nearly one day despite an absence of differences in other demographic and surgical factors other than age. Furthermore, there was a 50% reduction in readmission rates in the PET group. The use of a PET allows for healthcare professionals to engage, evaluate, and treat patients in a way that improves perioperative care.

Hepatitis E virus seropositivity in an ethnically diverse community blood donor population.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections. MATERIALS AND METHODS: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity. RESULTS: A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties. CONCLUSION: Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.