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Background Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children Methods Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine. The association between secretor and Lewis phenotypes and rotavirus vaccine failure was examined overall and by infecting rotavirus genotype using conditional logistic regression in 218 rotavirus-positive cases with moderate-to-severe diarrhea and 297 matched healthy controls. Results Both nonsecretor and Lewis-negative phenotypes (null phenotypes) were associated with decreased rotavirus vaccine failure across all sites (matched odds ratio, 0.30 [95% confidence interval: 0.16–0.56] or 0.39 [0.25–0.62], respectively]. A similar decrease in risk against rotavirus vaccine failure among null HBGA phenotypes was observed for cases with P[8] and P[4] infection and their matched controls. While we found no statistically significant association between null HBGA phenotypes and vaccine failure among P[6] infections, the matched odds ratio point estimate for Lewis-negative individuals was >4. Conclusions Our study demonstrated a significant relationship between null HBGA phenotypes and decreased rotavirus vaccine failure in a population with P[8] as the most common infecting genotype. Further studies are needed in populations with a large burden of P[6] rotavirus diarrhea to understand the role of host genetics in reduced rotavirus vaccine effectiveness.

A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing.

We present the discovery and characterization of six short-period, transiting giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) -- TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642), TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467). All six planets orbit bright host stars (8.9, Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRAS

Haiti introduced a monovalent human group A rotavirus (RVA) vaccine (Rotarix) into its routine infant immunization program in April 2014. The goal of the surveillance program was to characterize RVA strains circulating in Haiti before and after RVA vaccine introduction.Stool samples were collected from children5 years old presenting with acute gastroenteritis at 16 hospitals in Haiti. RVA antigen enzyme immunoassay (EIA) testing was performed, and G and P genotypes were determined for positive specimens. In this study, genotype data for samples collected from May 2012 through April 2014 (the pre-vaccine introduction era) and May 2014 through July 2019 (post-vaccine introduction era) were analyzed.A total of 809 specimens were tested by the Centers for Disease Control and Prevention. During the pre-vaccine introduction era (May 2012 through April 2014), G12P[8] was the predominant genotype, detected in 88-94% of specimens. There was a high prevalence of the equine-like G3P[8] genotype among Haitian children with RVA after vaccine introduction.The predominance of equine-like G3P[8] in three of five RVA seasons post-vaccine introduction suggests possible vaccine-specific selection pressure in Haiti. These temporal variations in RVA genotype predominance will require continued monitoring in Haiti as the vaccination program continues.

In this study, we report the detection of a G6P[14] rotavirus strain from a human stool sample within the United States. The full genotype constellation of the G6P[14] strain was identified as G6-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3.

Objectives. To assess SARS-CoV-2 transmission within a correctional facility and recommend mitigation strategies. Methods. From April 29 to May 15, 2020, we established the point prevalence of COVID-19 among incarcerated persons and staff within a correctional facility in Arkansas. Participants provided respiratory specimens for SARS-CoV-2 testing and completed questionnaires on symptoms and factors associated with transmission. Results. Of 1647 incarcerated persons and 128 staff tested, 30.5% of incarcerated persons (range by housing unit = 0.0%–58.2%) and 2.3% of staff tested positive for SARS-CoV-2. Among those who tested positive and responded to symptom questions (431 incarcerated persons, 3 staff), 81.2% and 33.3% were asymptomatic, respectively. Most incarcerated persons (58.0%) reported wearing cloth face coverings 8 hours or less per day, and 63.3% reported close contact with someone other than their bunkmate. Conclusions. If testing remained limited to symptomatic individuals, fewer cases would have been detected or detection would have been delayed, allowing transmission to continue. Rapid implementation of mass testing and strict enforcement of infection prevention and control measures may be needed to mitigate spread of SARS-CoV-2 in this setting.

Study Objectives Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioral processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest, and promote sleep. At present, little research has comprehensively characterized the neuropsychopharmacology of oxytocin-induced effects on sleep–wake behavior and no reconciliation of these two competing hypotheses has been proposed. Methods This study explored the effects of oxytocin on sleep–wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg−1) and intranasal (i.n.; 0.06, 1, 3 mg·kg−1) routes. Caffeine (i.p. and i.n.; 10 mg·kg−1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pretreatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg−1) followed by oxytocin (i.p.; 1 mg·kg−1) were also conducted. Results In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Several i.p. oxytocin-induced sleep–wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep–wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects. Conclusions These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep–wake behavior: i.p. oxytocin promotes quiet wakefulness—a state of restful environmental awareness compatible with both oxytocin’s anxiolytic effects and its enhancement of processing complex stimuli.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children’s stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year–vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive–vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year–vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive–vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

IntroductionSynthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances that have been associated with multiple instances and types of toxicity. Some SCRAs appear to carry a greater toxicological burden than others, or compared to the prototypical cannabis-derived agonist Δ9-tetrahydrocannabinol (Δ9-THC), despite a common primary mechanism of action via cannabinoid 1 (CB1) receptors. “Off-target” (i.e., non-CB1 receptor) effects could underpin this differential toxicity, although there are limited data around the activity of SCRAs at such targets.MethodsA selection of 7 SCRAs (AMB-FUBINACA, XLR11, PB-22, AKB-48, AB-CHMINICA, CUMYL-PINACA, and 4F-MDMB-BUTINACA), representing several distinct chemotypes and toxicological profiles, underwent a 30 μM single-point screen against 241 G protein-coupled receptor (GPCR) targets in antagonist and agonist mode using a cellular β-arrestin recruitment assay. Strong screening “hits” at specific GPCRs were followed up in detail using concentration-response assays with AMB-FUBINACA, a SCRA with a particularly notable history of toxicological liability.ResultsThe single-point screen yielded few hits in agonist mode for any compound aside from CB1 and CB2 receptors, but many hits in antagonist mode, including a range of chemokine receptors, the oxytocin receptor, and histamine receptors. Concentration-response experiments showed that AMB-FUBINACA inhibited most off-targets only at the highest 30 μM concentration, with inhibition of only a small subset of targets, including H1 histamine and α2B adrenergic receptors, at lower concentrations (≥1 μM). AMB-FUBINACA also produced concentration-dependent CB1 receptor signaling disruption at concentrations higher than 1 μM, but did not produce overt cytotoxicity beyond CP55,940 or Δ9-THC in CB1 expressing cells.DiscussionThese results suggest that while some “off-targets” could possibly contribute to the SCRA toxidrome, particularly at high concentrations, CB1-mediated cellular dysfunction provides support for hypotheses concerning on-target, rather than off-target, toxicity. Further investigation of non-GPCR off-targets is warranted.

IntroductionExogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioural processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest and promote sleep. At present, little research has comprehensively characterised the neuropsychopharmacology of oxytocin-induced effects on sleep-wake behaviour and no reconciliation of these two competing hypotheses has been proposed.MethodsThis study explored the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg-1) and intranasal (i.n.; 0.06, 1, 3 mg·kg-1) routes. Caffeine (i.p. and i.n.; 10 mg·kg-1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pre-treatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg-1) followed by oxytocin (i.p.; 1 mg·kg-1) were also conducted.ResultsIn both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, NREM and REM sleep. Several i.p. oxytocin-induced sleep-wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep-wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects.ConclusionsThese findings help reconcile competing hypotheses of oxytocin-induced effects on sleep-wake behaviour: i.p. oxytocin promotes quiet wakefulness—a state of restful environmental awareness compatible with both oxytocin’s anxiolytic effects and its enhancement of processing complex stimuli.

Background and purpose Cannabis has been used to treat epilepsy for millennia, with such use validated by regulatory approval of cannabidiol (CBD) for the treatment of Dravet syndrome. Unregulated artisanal cannabis-based products used to treat children with intractable epilepsies often contain relatively low doses of CBD but are enriched in other phytocannabinoids. This raises the possibility that other cannabis constituents might have anticonvulsant properties. Experimental approach We used the Scn1a+/- mouse model of Dravet syndrome to interrogate the cannabis plant for phytocannabinoids with anticonvulsant effects against hyperthermia-induced seizures. The most promising, cannabigerolic acid (CBGA), was further examined against spontaneous seizures and survival in Scn1a+/- mice. CBGA was also examined in conventional electroshock seizure models. In addition, we surveyed the pharmacological effects of CBGA across multiple drug targets. Key results The initial screen identified three phytocannabinoids with novel anticonvulsant properties: CBGA, cannabidivarinic acid (CBDVA) and cannabigerovarinic acid (CBGVA). CBGA was the most potent and potentiated the anticonvulsant effects of clobazam against hyperthermia-induced and spontaneous seizures, and was anticonvulsant in the MES threshold test. However, CBGA was proconvulsant in the 6-Hz threshold test and a high dose increased spontaneous seizure frequency in Scn1a+/- mice. CBGA was found to interact with numerous epilepsy-relevant targets including GPR55, TRPV1 channels and GABAA receptors. Conclusion These results suggest CBGA, CBDVA and CBGVA may contribute to the effects of cannabis-based products in childhood epilepsy. While these phytocannabinoids have anticonvulsant potential and could be lead compounds for drug development programs, several liabilities would need to be overcome before CBD is superseded by another in this class.

ObjectiveAutoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K.MethodsImmunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients.ResultsWe replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease.ConclusionOur data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.

We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.

BackgroundGroup A rotaviruses (RVA) are zoonotic pathogens responsible for acute enteritis in human and neonatal ruminants. This research aimed to determine the prevalence of RVA in ruminants (cattle, sheep, and goats) and investigate the circulating RVA genotypes in these animals in Kuwait. We conducted a cross-sectional study to detect RVA in ruminants, using an immunochromatography test (IC), direct sandwich ELISA test, and real-time RT-PCR (RT-qPCR) assay using fecal samples.ResultsA total of 400 cattle, 334 sheep, and 222 goats were examined. The prevalence of RVA was 5.3, 1.2, and 2.3%, respectively, using IC. The ELISA test detected RVA from 4.3% of cattle, 0.9% of sheep, and 1.8% of goats. There was a significant association between the occurrence of diarrhea and the presence of RVA in bovine fecal samples (p-value = 0.0022), while no statistical association between diarrhea and the presence of RVA in fecal samples of sheep and goats was observed (p-value = 0.7250;p-value = 0.4499, respectively). Twenty-three of the IC-positive samples (17 from cattle, two from sheep, and four from goats) were tested using a RT-qPCR RVA detection assay targeting the NSP3 gene. The results showed that 21 of 23 IC-positive samples tested positive by RT-qPCR. Detection of RVA genotypes revealed that G10P[11] was the predominant strain in cattle (58.8%), followed by G8P[1] (11.7%). One sheep sample was genotyped as G8P[1]. In addition, G6P[1] and G6P[14] were detected in goat samples.ConclusionThe present study revealed that the IC was more sensitive in detecting RVA antigen in fecal samples than the ELISA test. A higher occurrence of RVA infection was observed in cattle than in sheep and goats. This study suggests that RVA might be a risk factor of diarrhea in bovine calves less than 2 weeks old. This research also demonstrates the circulation of RVA in sheep and goat populations in Kuwait. Finally, the G10P[11] RVA genotype was the most prevalent genotype identified from cattle samples.

Type 2 diabetes is a chronic disease that affects millions of Americans and puts a significant burden on the healthcare system. The medical community sees screening patients to identify and treat prediabetes and diabetes early as an important goal; however, universal population screening is operationally not feasible, and screening policies need to take characteristics of the patient population into account. For instance, the screening policy for a population in an affluent neighborhood may differ from that of a safety‐net hospital. The problem of optimal diabetes screening—whom to screen and when to screen—is clearly important, and small improvements could have an enormous impact. However, the problem is typically only discussed from a practical viewpoint in the medical literature; a thorough theoretical framework from an operational viewpoint is largely missing. In this study, we propose an approach that builds on multiple methods—partially observable Markov decision process (POMDP), hidden Markov model (HMM), and predictive risk modeling (PRM). It uses available clinical information, in the form of electronic health records (EHRs), on specific patient populations to derive an optimal policy, which is used to generate screening decisions, individualized for each patient. The POMDP model, used for determining optimal decisions, lies at the core of our approach. We use HMM to estimate the cohort‐specific progression of diabetes (i.e., transition probability matrix) and the emission matrix. We use PRM to generate observations—in the form of individualized risk scores—for the POMDP. Both HMM and PRM are learned from EHR data. Our approach is unique because (i) it introduces a novel way of incorporating predictive modeling into a formal decision framework to derive an optimal screening policy; and (ii) it is based on real clinical data. We fit our model using data on a cohort of more than 60,000 patients over 5 years from a large safety‐net health system and then demonstrate the model's utility by conducting a simulation study. The results indicate that our proposed screening policy outperforms existing guidelines widely used in clinical practice. Our estimates suggest that implementing our policy for the studied cohort would add one quality‐adjusted life year for every patient, and at a cost that is 35% lower, compared with existing guidelines. Our proposed framework is generalizable to other chronic diseases, such as cancer and HIV.

Interprofessional collaboration (IPC) has been shown to improve healthcare quality and patient safety; however, formal interprofessional education (IPE) training is insufficient. The VA Quality Scholars (VAQS) program exists to develop interprofessional leaders and scholars in healthcare improvement. The purpose of this study was to examine the impact of integrating interprofessional healthcare learners and designing an interprofessional curriculum for the national VAQS program. VAQS alumni (graduates from 2001 to 2017) across eight national sites (n = 102 [53.1%]) completed a web-based survey to assess alumni perceptions of IPC skill development during the program and IPC skill utilization in their careers. Alumni from 2009 and earlier were physicians; alumni after 2009 came from diverse health professional backgrounds. Overall, IPC and teamwork was identified as the most used skill (n = 82, 70%) during their career. When comparing the pre-IPE period and the post-IPE period, post-IPE alumni identified IPC and teamwork as the area of greatest skill development (n = 38). Integrating interprofessional trainees and robust IPE curricula enhanced an established and successful quality improvement (QI) training program. VAQS alumni endorsed the importance of IPC skills during their careers. The VAQS program is an example of how health professionals can successfully learn IPC skills in healthcare QI.

OBJECTIVE: To determine and evaluate the accuracy of methods physicians use to detect diagnostic criteria for pediatric hypertension (hypertensive BPs on ≥3 occasions) in electronic health records (EHRs). METHODS: Methods used by pediatric-trained physicians (n=12) to detect diagnostic criteria for hypertension in a simulation using a child’s EHR data were directly observed, timed, and evaluated for accuracy. All physicians were given the same information regarding diagnostic criteria to eliminate knowledge gaps. Then, computer modeling and EHR data from 41,654 3–18-year-olds were used to simulate and compare the accuracy of detecting hypertension criteria using an observed-shorthand method vs. the guideline-recommended/gold-standard method. RESULTS: No physician used the guideline-recommended method of determining multiple time-of-care hypertension thresholds for child age/height at the time of each BP measure. One physician estimated the child’s BP diagnosis without computing thresholds; 11/12 physicians determined the child’s hypertension threshold from age/height data at the time of a current visit and applied/imputed this threshold to BP measured at all visits (current-visit threshold used to assess historical-visit BPs) to detect three separate BP elevations. Physicians took 2.3 minutes (95% CI, 1.5–3.0) to declare a diagnosis. Sensitivity was 83.1% when applying the current-visit threshold to detect the guideline-recommended-BP-threshold diagnosis using EHR data. Specificity and positive-/negative-predictive values ranged from 98.5–99.9%. CONCLUSIONS: Physicians applied a shorthand method to evaluate pediatric BPs. Computer-simulated comparison of the shorthand and guideline methods using clinical data suggests the shorthand method could yield an inaccurate impression of a child’s BP history in 17% of pediatric ambulatory visits. CONDENSED ABSTRACT: Complex computation of blood-pressure thresholds during outpatient visits has been cited as an impediment to diagnosing pediatric hypertension. Guidelines recommend clinicians recognize blood pressures exceeding hypertension thresholds at ≥3 separate visits. It was unclear if physicians use this method. Observation of physicians identified use of a single hypertension threshold indexed to a child’s age and height at an active visit, not the threshold for age/height at the time of previous visits to detect if a child meets diagnostic criteria for hypertension. Comparison of this practical-though-imperfect method with the guideline-recommended method revealed physicians may miss many children meeting guideline-recommended hypertension criteria.

Objective Rotavirus A (RVA) remains the main causative agent of gastroenteritis in young children and the young of many mammalian and avian species. In this study we describe a RVA strain detected from a 6-month-old child from Central African Republic (CAR). Results We report the 11 open reading frame sequences of a G29-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 rotavirus strain, RVA/Human-wt/CAR/CAR91/2014/G29P[6]. Nine genes (VP1–VP3, VP6, NSP1–NSP5) shared 90–100% sequence similarities with genogroup 2 rotaviruses. Phylogenetically, backbone genes, except for VP3 and NSP4 genes, were linked with cognate gene sequences of human DS-1-like genogroup 2, hence their genetic origin. The VP3 and NSP4 genes, clustered genetically with both human and animal strains, an indication genetic reassortment human and animal RVA strains has taken place. The VP7 gene shared nucleotide (93–94%) and amino acid (95.5–96.7%) identities with Kenyan and Belgian human G29 strains, as well as to buffalo G29 strain from South Africa, while the VP4 gene most closely resembled P[6]-lineage I strains from Africa and Bangladesh (97%).

Cannabis sativa contains >120 phytocannabinoids, but our understanding of these compounds is limited. Determining the molecular modes of action of the phytocannabinoids may assist in their therapeutic development. Ligand-based virtual screening was used to suggest novel protein targets for phytocannabinoids. The similarity ensemble approach, a virtual screening tool, was applied to target identification for the phytocannabinoids as a class and predicted a possible interaction with the lactate dehydrogenase (LDH) family of enzymes. In order to evaluate this in silico prediction, a panel of 18 phytocannabinoids was screened against two LDH isozymes (LDHA and LDHB) in vitro. Cannabichromene (CBC) and Δ9-tetrahydrocannabinolic acid (Δ9-THCA) inhibited LDHA via a noncompetitive mode of inhibition with respect to pyruvate, with Ki values of 8.5 and 6.5 μM, respectively. In silico modeling was then used to predict the binding site for CBC and Δ9-THCA. Both were proposed to bind within the nicotinamide pocket, overlapping the binding site of the cofactor NADH, which is consistent with the noncompetitive modes of inhibition. Stemming from our in silico screen, CBC and Δ9-THCA were identified as inhibitors of LDHA, a novel molecular target that may contribute to their therapeutic effects.

Background Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. Methods Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. Results Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3–15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03–.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4–.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6–65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values Conclusions SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.

Background Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014–2016 Methods A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. Results A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens. Conclusions G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.

Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005−2009. Children aged

Rwanda was the first low-income African country to introduce RotaTeq vaccine into its Expanded Programme on Immunization in May 2012. To gain insights into the overall genetic make-up and evolution of Rwandan G1P[8] strains pre- and post-vaccine introduction, rotavirus positive fecal samples collected between 2011 and 2016 from children under the age of 5 years as part of ongoing surveillance were genotyped with conventional RT-PCR based methods and whole genome sequenced using the Illumina MiSeq platform. From a pool of samples sequenced (n = 158), 36 were identified as G1P[8] strains (10 pre-vaccine and 26 post-vaccine), of which 35 exhibited a typical Wa-like genome constellation. However, one post vaccine strain, RVA/Human-wt/RWA/UFS-NGS:MRC-DPRU442/2012/G1P[8], exhibited a RotaTeq vaccine strain constellation of G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3, with most of the gene segments having a close relationship with a vaccine derived reassortant strain, previously reported in USA in 2010 and Australia in 2012. The study strains segregated into two lineages, each containing a paraphyletic pre- and post-vaccine introduction sub-lineages. In addition, the study strains demonstrated close relationship amongst each other when compared with globally selected group A rotavirus (RVA) G1P[8] reference strains. For VP7 neutralization epitopes, amino acid substitutions observed at positions T91A/V, S195D and M217T in relation to the RotaTeq vaccine were radical in nature and resulted in a change in polarity from a polar to non-polar molecule, while for the VP4, amino acid differences at position D195G was radical in nature and resulted in a change in polarity from a polar to non-polar molecule. The polarity change at position T91A/V of the neutralizing antigens might play a role in generating vaccine-escape mutants, while substitutions at positions S195D and M217T may be due to natural fluctuation of the RVA. Surveillance of RVA at whole genome level will enhance further assessment of vaccine impact on circulating strains, the frequency of reassortment events under natural conditions and epidemiological fitness generated by such events.