Personalised blood pressure management during major noncardiac surgery and postoperative neurocognitive disorders: a randomised trial.

Background: It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised-compared to routine-intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery. Methods: In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure [MAP] above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7. Results: The primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio [OR]=0.84, 95% confidence interval [CI]: 0.40-1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45-2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04-3.53, P=0.684). Conclusions: Personalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome-delayed neurocognitive recovery and delirium-compared to routine blood pressure management in patients having major noncardiac surgery. Clinical trial registration: ClinicalTrials.gov (NCT03442907).

Effectiveness of implementing evidence-based approaches to promote physical activity in a Midwestern micropolitan area using a quasi-experimental hybrid type I study design.

BACKGROUND: Much evidence-based physical activity (PA) interventions have been tested and implemented in urban contexts. However, studies that adapt, implement, and evaluate the effectiveness of these interventions in micropolitan rural contexts are needed. The study aimed to evaluate the effectiveness of the Active Ottumwa intervention to promote PA in a micropolitan community. METHODS: Between 2013 - 2019, we implemented Active Ottumwa in a micropolitan setting, and subsequently implemented and evaluated its effectiveness using a Hybrid Type I design. In this paper, we describe the intervention's effectiveness in promoting PA. We collected PA data over 24 months from a cohort of community residents using accelerometers and PA data from two cross-sectional community surveys administered in 2013 and 2018, using the Global Physical Activity Questionnaire. RESULTS: From the cohort, we found significant change in PA over 24 months (P = 0.03) corresponding to a 45-min daily decrease in sedentary activity, a daily increase of 35-min in light PA and 9 min in moderate-to-vigorous PA. There was a statistically significant (P = 0.01) increasing trend at the population-level in the moderate-to-vigorous composition of 7 min between the two cross-sectional assessments (95% CI: 0.1%-1.34%). CONCLUSIONS: The study demonstrates that the adapted evidence-based PA interventions in a micropolitan context is effective.

Anti-Markovnikov Hydroalkylation of Styrene Derivatives via Hydrazones Catalyzed by Ru-PNP Complex.

A well-defined Ru(II)-PNP complex demonstrated high activity in the anti-Markovnikov hydroalkylation of nonpolarized terminal alkenes via hydrazones. Hydrazone served as a carbanion equivalent to combine with the electrophilic alkene substrate upon activation by the ruthenium catalyst, forming a new C-C bond in a concerted pathway with N2 as the only theoretical byproduct. Experimental and computational studies suggested the existence of a push-pull interaction that activated the alkene for hydrazone addition and then deduced the mechanism.

Prediction of highly stable 2D carbon allotropes based on azulenoid kekulene.

Despite enormous interest in two-dimensional (2D) carbon allotropes, discovering stable 2D carbon structures with practically useful electronic properties presents a significant challenge. Computational modeling in this work shows that fusing azulene-derived macrocycles - azulenoid kekulenes (AK) - into graphene leads to the most stable 2D carbon allotropes reported to date, excluding graphene. Density functional theory predicts that placing the AK units in appropriate relative positions in the graphene lattice opens the 0.54 eV electronic bandgap and leads to the appearance of the remarkable 0.80 eV secondary gap between conduction bands - a feature that is rare in 2D carbon allotropes but is known to enhance light absorption and emission in 3D semiconductors. Among porous AK structures, one material stands out as a stable narrow-multigap (0.36 and 0.56 eV) semiconductor with light charge carriers (me = 0.17 m0, mh = 0.19 m0), whereas its boron nitride analog is a wide-multigap (1.51 and 0.82 eV) semiconductor with light carriers (me = 0.39 m0, mh = 0.32 m0). The multigap engineering strategy proposed here can be applied to other carbon nanostructures creating novel 2D materials for electronic and optoelectronic applications.

A Clinical Suspicion of Quetiapine-Induced Psychosis: A Case Report and Literature Review.

Quetiapine, a pharmacological agent within the class of atypical antipsychotics, is characterized by its efficacy in mood stabilization and its role in the modulation of serotonergic and dopaminergic pathways. Its therapeutic utility is broad, encompassing the management of acute psychotic episodes, schizophrenia, bipolar disorder, and treatment-resistant depressive states. Quetiapine's effectiveness extends to depressive disorders that do not exhibit classic psychotic features, with a side effect profile that is less burdensome than many alternative psychotropic medications. Its versatility in addressing a range of psychiatric conditions is useful in the psychopharmacological management of mood and thought disorders. However, like all drugs, quetiapine may have different effects relative to the individual. It is imperative to approach the administration of quetiapine carefully, ensuring any adverse effects are ameliorated for beneficial therapeutic outcomes. In this case report, we present a psychosis-naive 42-year-old male who developed psychotic symptoms after beginning a quetiapine regimen in order to manage major depressive disorder with suicidal ideation. Clinical suspicion of quetiapine-induced psychosis was a diagnosis considered due to symptom remission secondary to ziprasidone in the place of quetiapine. The determination of a suspected adverse drug reaction can utilize the Naranjo scale to demonstrate the likelihood of an adverse drug reaction. This patient scored a three on the Naranjo scale, indicating a possible adverse effect from quetiapine. Other potential etiologies of psychosis include medication-induced psychosis, major depressive disorder exacerbation, cocaine use/withdrawal, and brief psychotic disorder. Quetiapine-induced psychosis has not been described in the current literature, and therefore, this case report is solely based on clinical evaluation and is intended for educational purposes due to possible confounding factors and etiologies.

Evaluation of a Moisturizing Cream with 20% Urea for Keratosis Pilaris.

BACKGROUND: Keratosis pilaris (KP) is a benign dermatosis consisting of folliculocentric keratotic papules or pustules with surrounding erythema, often on proximal extensor surfaces of extremities. Management strategies for KP largely center on moisturization and exfoliation. Urea, a well-established ingredient in topical skincare, is a component of the natural moisturizing factors with concentration-dependent humectant, emollient, and exfoliative properties.  Given the overlap of urea’s properties and management goals of KP, a 4-week, open-label, noncomparative clinical study was conducted to evaluate a moisturizing cream formulated with 20% urea for use in KP.  Thirty participants aged 18 to 65 years with KP completed this study. After a 5-day washout period, study participants applied a 20% urea cream once daily to areas of KP for 4 weeks. At baseline, 1-week, and 4-week visits, clinical grading of skin texture, adverse event monitoring, and participant satisfaction questionnaires were conducted. After 1 week and 4 weeks of product use, the percent change in skin smoothness/texture from baseline was significant (P≤0.001). Furthermore, after 4 weeks of use, the majority of participants indicated satisfaction with the feel of their skin, as well as improved confidence and decreased embarrassment related to their skin. No significant adverse events were reported. Overall, the results of this study support that 20% urea cream is generally well tolerated and suitable for use in treating KP. J Drugs Dermatol. 2024;23(1):1274-1277.     doi:10.36849/JDD.7806.

Community and Organizational Readiness to Adopt a Physical Activity Intervention in Micropolitan Settings.

BACKGROUND: Assessing community and organizational readiness is key to successfully implementing programs. The purpose of this study was to assess the baseline readiness of micropolitan communities to adopt an evidence-based physical activity (PA) intervention by exploring three dimensions: (1) attitudes and current efforts toward prevention, (2) community and organizational climate that facilitates (or impedes) change, and (3) capacity to implement change. METHOD: Data were collected from community leaders in 14 communities through an online survey in June 2021 (n = 149). Data were analyzed in aggregate using descriptive statistics for multiple-choice responses and content analysis for open ended responses. One-way repeated analyses of variance were used to compare mean score differences. RESULTS: In reference to their attitudes prior to the pandemic, respondents said that addressing PA was "somewhat a priority" in their professional positions (M = 2.01, SD = 0.94), their organizations (M = 2.08, SD = 0.91), and their communities (M = 2.28, SD = 0.88). Current PA efforts included statewide initiatives, community sponsored events/clubs, and youth sports leagues. The community climate included both PA facilitators (mainly outdoor PA resources) and barriers (cost, lack of social services, and an unsupportive PA environment). Individual-level capacity (M = 2.94; SD = 1.21) to adopt a PA program was regarded lower than the community's capacity (M = 3.95; SD = 0.82), and perceptions of capacity at the community level improved even more if technical assistance (M = 3.96; SD = 0.84) or financial support (M = 4.12; SD = 0.80) were provided. CONCLUSION: Readiness varied by dimension, suggesting the need for tailored implementation supports including technical assistance and financial support.

Controlling posture to see the world: The integration of visual task demands and postural sway in sitting and standing infants.

Our ability to integrate posture with visually demanding tasks is a critical aspect of motor behavior flexibility. When looking at a small object, excessive body movements impair an individual's ability to visually attend to the object. To overcome this problem, we adjust our postural sway to successfully focus on the object. The goal of the current study was to assess whether infants also adjust postural sway when engaged in a challenging visual task. The participants, 19 independently sitting infants (Sitters) and 21 newly independently standing infants (Standers), sat or stood on a force plate while viewing differently sized images displayed on a monitor (smaller images: 8 × 6.5 cm or 3 × 3 cm; larger images: 13 × 16 cm or 13 × 13 cm). Regardless of image size, Standers were less stable than Sitters with larger sway areas and faster sway velocities. Both Sitters and Standers adjusted sway area but not sway velocity, based on image size. Sitters and Standers differed in how they controlled sway dynamics. Standers but not Sitters altered sway dynamics based on image size. Overall, infants used posture-specific adaptive control strategies to make fine-grained adjustments based on image size. The development of the ability to integrate posture with a visually demanding task further emphasizes the capability of advanced complex motor behaviors during infancy, enabling infants to flexibly attend to important aspects of their environment at different postural positions.

Serotonergic Medication Error: A Case Report of Serotonin Syndrome.

Serotonin syndrome (SS) describes a life-threatening clinical condition that can develop within hours or days after taking serotonergic medication(s). Medication adverse reactions, overdose, or drug interactions can cause this syndrome. Patients often present with symptoms of hyperthermia, muscle rigidity, hyperreflexia, and clonus. Symptoms range broadly in severity, often influenced by polypharmacy and age. In this report, SS was diagnosed in an elderly patient who presented with diffuse urticaria and exacerbated tremor. These complaints were thought to be associated with Parkinson's disease due to a strong family history. Clinicians are encouraged to consider SS in their differential diagnosis when dealing with elderly patients with multiple medications, psychiatric diagnoses, conditions managed by other providers, and/or a strong family history of neurodegenerative diseases.

Racial and ethnic disparities in biomarkers of exposure and potential harm among U.S. adult exclusive e-cigarette users: 2013-2019.

OBJECTIVE: Provide evidence on racial and ethnic differences in biomarkers of exposure from rising e-cigarette use among U.S. adults. METHODS: Data were drawn from Waves 1-5 of the Population Assessment of Tobacco and Health study (September 2013-November 2019). Differences in biomarkers of exposure and potential harm (BOE/BoPH) across non-Hispanic (NH)-Whites, NH Blacks, Hispanic/Latinos, and NH others were examined using generalized estimation equations. RESULTS: Among exclusive e-cigarette users, mean concentrations of BOEs/BoPHs were not significantly different across NH Blacks (n=97), NH others (n=122), and NH Whites (n=1062), after adjustment by wave, age, sex, education, exposure to the secondhand smoke, and the number of recent puffs. Compared to NH Whites, Hispanics (n=151) had lower concentrations of nicotine equivalents (0.5[0.2-1.7] vs. 15.5 [12.5-19.1] nmol/mg creatinine, p<.0001), cotinine (33.4[9.7-114.7] vs. 1008.3 [808.3-1257.9] ng/mg creatinine, p<.0001), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (2.6[1.5-4.4] vs. 5.7 [4.9-6.6] pg/mg creatinine, p=.004), but similar concentrations of BOEs for heavy metals, polycyclic aromatic hydrocarbons, volatile organic compounds, and oxidative stress. Differences between Hispanics and NH Whites are expected, given different e-cigarette use profiles. Specifically, Hispanics were less likely to be daily vapers (49.4[35.1-63.8]% vs 81.3[77.7-84.5]%, p<.0001) and nicotine e-cigarette users (72.7 [64.0-79.9]% vs. 89.2 [86.4-91.5]%, p=.0002] and reported a lower number of recent puffs (mean[standard error]=16.7[3.6] vs. 28.6[2.0], p=.02] than their NH-White counterparts. Hispanic vapers were also less likely than NH Whites to have previously smoked cigarettes (49.7 [37.2-62.3]% vs. 88.5 [84.7-91.5]%, p<.0001]). CONCLUSIONS: Hispanic vapers exhibited lower exposure to nicotine metabolites and carcinogens than their non-Hispanic White counterparts. The harm reduction potential from e-cigarette use are likely to be realized across diverse racial and ethnic groups.

Genetic Architecture of Salt Tolerance in Cowpea (Vigna unguiculata (L.) Walp.) at Seedling Stage Using a Whole Genome Resequencing Approach.

Cowpea (Vigna unguiculata (L.) Walp.) is a diploid legume crop used for human consumption, feed for livestock, and cover crops. Earlier reports have shown that salinity has been a growing threat to cowpea cultivation. The objectives of this study were to conduct a genome-wide association study (GWAS) to identify SNP markers and to investigate candidate genes for salt tolerance in cowpea. A total of 331 cowpea genotypes were evaluated for salt tolerance by supplying a solution of 200 mM NaCl in our previous work. The cowpea panel was genotyped using a whole genome resequencing approach, generating 14,465,516 SNPs. Moreover, 5,884,299 SNPs were used after SNP filtering. GWAS was conducted on a total of 296 cowpea genotypes that have high-quality SNPs. BLINK was used for conducting GWAS. Results showed (1) a strong GWAS peak on an 890-bk region of chromosome 2 for leaf SPAD chlorophyll under salt stress in cowpea and harboring a significant cluster of nicotinamide adenine dinucleotide (NAD) dependent epimerase/dehydratase genes such as Vigun02g128900.1, Vigun02g129000.1, Vigun02g129100.1, Vigun02g129200.1, and Vigun02g129500.1; (2) two GWAS peaks associated with relative tolerance index for chlorophyll were identified on chromosomes 1 and 2. The peak on chromosome 1 was defined by a cluster of 10 significant SNPs mapped on a 5 kb region and was located in the vicinity of Vigun01g086000.1, encoding for a GATA transcription factor. The GWAS peak on chromosome 2 was defined by a cluster of 53 significant SNPs and mapped on a 68 bk region of chromosome 2, and (3) the highest GWAS peak was identified on chromosome 3, and this locus was associated with leaf score injury. This peak was within the structure of a potassium channel gene (Vigun03g144700.1). To the best of our knowledge, this is one the earliest reports on the salt tolerance study of cowpea using whole genome resequencing data.

Screening Y Chromosome Microdeletion in 1121 Men with Low Sperm Concentration and the Outcomes of Microdissection Testicular Sperm Extraction (mTESE) for Sperm Retrieval from Azoospermic Patients.

Background: The Y chromosome has a specific region, namely the Azoospermia Factor (AZF) because azoospermia is typically reported in the microdeletion of the AZF region. This study aims to assess the characteristics of AZF microdeletion after screening a massive number of low sperm concentration men; and the Microdissection testicular sperm extraction (mTESE) outcomes for retrieving sperm from azoospermic patients. Materials and Methods: This retrospective multiple-center study enrolled a total of 1121 men with azoospermia, cryptozoospermia, and severe oligozoospermia from December 2016 to June 2022. An extension analysis used a total of 17 STSs to detect the position-occurring microdeletion in the AZF region (AZFa, b, c, and/or d loci). Microdissection testicular sperm extraction (mTESE) was performed to retrieve sperm in azoospermic men diagnosed AZFc microdeletion. Results: One hundred and fifty-three men carried AZF microdeletion were detected in the 1121 participants (13.64%). The incidences of AZF microdeletion were confined to AZF a, c, and d regions, both individual and concurrence, with the most common in the AZFc region accounting for 49.67%; There was no significant difference in clinical and paraclinical characteristics between the deleted regions, except FSH level (highest in AZFa microdeletion, p = 0.043). The AZFc region was the most common type of AZF microdeletion (49.67%), including complete microdeletion (4 patients) and gr/gr partial microdeletion (39 patients) with 50.00% and 63.63% in the success rate of mTESE, separately. Conclusion: The absence of AZFa and/or AZFb regions often express the most severe phenotype - azoospermia and the increasing FSH level. The AZFc region played the most common microdeletion. Microdissection testicular sperm extraction (mTESE) was the possible therapy for sperm retrieval from the testis of azoospermia men having AZFc microdeletion.

Ignored and distressed: a cross-sectional study of the impact of COVID-19 on last responders.

BACKGROUND: Last responders constitute an occupational category that includes all those that are involved in the postmortem care of deceased persons and their families. Last responders are exposed to several categories of work-related stressors that affect their health and well-being. COVID-19 exacerbated these stressors. Research to understand the consequences of COVID-19 on the health and wellbeing of last responders is nascent. This study aimed to assess COVID-19 related stress, coping and wellbeing among last responders in the United States. METHODS: We conducted a national cross-sectional survey of last responders in July through September of 2020. The survey measured wellbeing, stress, coping, and stigma; COVID-19 experiences, and socio-demographics. A ridge regression model was fit for the outcome variables. RESULTS: Analysis was conducted on 366 respondents from 43 states. Respondents were male (55.4%), age 50 + (57.4%), and White non-Hispanic (90.3%); 54% reported moderate-high stress and 41% endorsed mild-severe anxiety. Seventy-seven percent had experienced at least one form of stigma related to their occupation. Variables associated with higher perceived stress and anxiety included gender (female), shorter length of employment, perceiving a higher impact from COVID-19 on everyday life, and increased perceived stigma. CONCLUSIONS: Last responders are a critical part of the health care system. Throughout this pandemic, last responders have been frequently ignored and not prioritized for protection and support. Interventions to support last responders cope with stress, and to decrease anxiety are urgently needed. There is also a critical need to challenge community stigma towards last responders.

Impact of a switch to immediate release on the patient viewing of diagnostic test results in an online portal at an academic medical center.

Patient portals allow patients to access their personal health information. The 21st Century Cures Act in the United States sought to eliminate 'information blocking', requiring timely release upon request of electronic health information including diagnostic test results. Some health systems, including the one in the present study, chose a systematic switch to immediate release of all or nearly all diagnostic test results to patient portals as part of compliance with the Cures Act. Our primary objective was to study changes in the time to view test results by patients before and after implementation of Cures Act-related changes. This retrospective pre-post study included data from two 10-month time periods before and after implementation of Cures Act-related changes at an academic medical center. The study included all patients (adult and pediatric) with diagnostic testing (laboratory and imaging) performed in the outpatient, inpatient, or emergency department settings. Between February 9, 2020 and December 9, 2021, there was a total of 3 809 397 diagnostic tests from 204 605 unique patients (3 320 423 tests for adult patients; 488 974 for pediatric patients). Overall, 56.5% (115 627) of patients were female, 84.1% (172 048) white, and 96.5% (197 517) preferred English as primary language. The odds of viewing test results within 1 and 30 days after portal release increased monthly throughout both time periods before and after the Cures Act for all patients. The rate of increase was significantly higher after implementation only in the subgroup of tests belonging to adult patients with active MyChart accounts. Immediate release shifted a higher proportion of result/report release to weekends (3.2% pre-Cures vs 15.3% post-Cures), although patient viewing patterns by day of week and time of day were similar before and after immediate release changes. The switch to immediate release of diagnostic test results to the patient portal resulted in a higher fraction of results viewed within 1 day across outpatient, inpatient, and emergency department settings.

Bipartite genome and structural organization of the parvovirus Acheta domesticus segmented densovirus.

Parvoviruses (family Parvoviridae) are currently defined by a linear monopartite ssDNA genome, T = 1 icosahedral capsids, and distinct structural (VP) and non-structural (NS) protein expression cassettes within their genome. We report the discovery of a parvovirus with a bipartite genome, Acheta domesticus segmented densovirus (AdSDV), isolated from house crickets (Acheta domesticus), in which it is pathogenic. We found that the AdSDV harbors its NS and VP cassettes on two separate genome segments. Its vp segment acquired a phospholipase A2-encoding gene, vpORF3, via inter-subfamily recombination, coding for a non-structural protein. We showed that the AdSDV evolved a highly complex transcription profile in response to its multipartite replication strategy compared to its monopartite ancestors. Our structural and molecular examinations revealed that the AdSDV packages one genome segment per particle. The cryo-EM structures of two empty- and one full-capsid population (3.3, 3.1 and 2.3 Å resolution) reveal a genome packaging mechanism, which involves an elongated C-terminal tail of the VP, "pinning" the ssDNA genome to the capsid interior at the twofold symmetry axis. This mechanism fundamentally differs from the capsid-DNA interactions previously seen in parvoviruses. This study provides new insights on the mechanism behind ssDNA genome segmentation and on the plasticity of parvovirus biology.

Effectiveness of a New Clinical and Communication Curriculum for Medical Students: Result of a Double-Blinded Randomized Controlled Educational Trial.

OBJECTIVES: To improve 4 skills (communication, history-taking, past history-taking, and documentation) in medical students, we designed and pilot-tested a curriculum to teach a sample of Year 4 (Y4) students these skills and compared the clinical performance of these students with students not receiving the intervention. METHODS: The study focused on the new curriculum's effectiveness in enhancing students' performance of these skills. To minimize exposure across groups, participants were divided into intervention and control groups at random and placed in various classrooms. We evaluated each group's clinical competency 3 times: prior to the intervention, 9 weeks afterward, and 2 years later. RESULTS: There was no difference at baseline between the 2 groups. Immediately following the intervention, the mean score of the intervention group's skills was significantly higher than before and higher than the control group in each clinical skill. The performance difference between the 2 groups was maintained for 2 years following the intervention. CONCLUSIONS: Following a 9-week curriculum, evaluators rated students' performance higher than their counterparts who learned these skills through standard informal exposure in the clinical setting. The fact that this performance advantage was maintained for 2 years following the intervention is a testament to the durability of the intervention and the value of dedicated training in these critical areas at an early point in students' clinical careers.

Monitoring the effects of urbanization and flood hazards on sandy ecosystem services.

Urbanization, storms, and floods have compromised the benefits derived from various types of sand dune landscapes, particularly in developing countries located in humid monsoon tropical regions. One pertinent question is which driving forces have had a dominant impact on the contributions of sand dune ecosystems to human well-being. Has the decline in sand dune ecosystem services (ES) been primarily due to urbanization or flooding hazards? This study aims to address these issues by developing a Bayesian Belief Network (BBN) to analyze six different sand dune landscapes worldwide. The study uses various data types, including multi-temporal and -sensor remote sensing (SAR and optical data), expert knowledge, statistics, and GIS to analyze the trends in sand dune ecosystems. A support tool based on probabilistic approaches was developed to assess changes in ES over time due to the effects of urbanization and flooding. The developed BBN has the potential to assess the ES values of sand dunes during both rainy and dry seasons. The study calculated and tested the ES values in detail over six years (from 2016 to 2021) in Quang Nam province, Vietnam. The results showed that urbanization has led to an increase in the total ES values since 2016, while floods only had a minimal impact on dune ES values during the rainy season. The fluctuations of ES values were found to be more significant due to urbanization than floods. The study's approach can be useful in future research on coastal ecosystems.

Students supporting students: evaluating the impact of the COVID-19 pandemic on resident assistant mental health.

OBJECTIVE: To examine the impact of the novel coronavirus SARS-CoV2 (COVID-19) pandemic on Residents Assistants (RA) at a public university in the Midwest. PARTICIPANTS: Sixty-seven RAs that had been offered an RA position for the '20-'21 academic year. METHODS: An online cross-sectional survey measuring socio-demographics, stress, and well-being was fielded. MANCOVA models evaluated the impact of COVID-19 on well-being of Current RAs and compared to the non-current RA groups. RESULTS: Sixty-seven RAs provided valid data. Overall, 47% of RAs had moderate-severe anxiety and 86.3% had moderate-high level of stress. Current RAs perceiving a great impact of COVID on life had significantly more stress, anxiety, burnout, and secondary traumatic stress than those who did not. RAs who started then quit experienced significantly higher secondary trauma compared to Current RAs. CONCLUSIONS: Further research is needed to better understand the experiences and of RAs and to develop policies and programs to support RAs.

The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.

Human immunodeficiency virus (HIV) treatment with antiretroviral regimens containing integrase strand transfer inhibitors such as dolutegravir (DTG) and bictegravir (BIC) offers high levels of protection against the development of drug resistance mutations. Despite this, resistance to DTG and BIC can occur through the development of the R263K integrase substitution. Failure with DTG has also been associated with the emergence of the G118R substitution. G118R and R263K are usually found separately but have been reported together in highly treatment-experienced persons who experienced treatment failure with DTG. We used cell-free strand transfer and DNA binding assays and cell-based infectivity, replicative capacity, and resistance assays to characterize the G118R plus R263K combination of integrase mutations. R263K reduced DTG and BIC susceptibility ~2-fold, in agreement with our previous work. Single-cycle infectivity assays showed that G118R and G118R plus R263K conferred ~10-fold resistance to DTG. G118R alone conferred low levels of resistance to BIC (3.9-fold). However, the G118R plus R263K combination conferred high levels of resistance to BIC (33.7-fold), likely precluding the use of BIC after DTG failure with the G118R plus R263K combination. DNA binding, viral infectivity, and replicative capacity of the double mutant were further impaired, compared to single mutants. We propose that impaired fitness helps to explain the scarcity of the G118R plus R263K combination of integrase substitutions in clinical settings and that immunodeficiency likely contributes to its development.

The utility of renal medullary pyramidal thickness measurements on the first and second postnatal ultrasound in infants with congenital hydronephrosis.

INTRODUCTION: Prior studies with postnatal ultrasound measurements of the medullary pyramid thickness (PT) demonstrate a PT < 3 mm as a significant risk factor for the diagnosis of UPJ obstruction and pyeloplasty. These studies used the postnatal ultrasound demonstrating the largest degree of hydronephrosis. Since early identification of children at increased risk of obstruction and pyeloplasty would be clinically useful, we reviewed the PT on the first and second postnatal ultrasound in infants with congenital hydronephrosis. OBJECTIVE: The aims of the study were to determine the prognostic value of: 1) PT on the first and second postnatal ultrasound, 2) a change in PT between first and second ultrasounds, and 3) ratio of PT in the hydronephrotic kidney to the contralateral PT in the normal kidney in those with unilateral hydronephrosis. We hypothesized that a smaller PT on either the first or second ultrasound, as well as a decreasing PT between the first and second ultrasound, and a decreased ratio of hydronephrotic PT to the contralateral normal kidney, would each be early predictors of subsequent pyeloplasty. STUDY DESIGN: A retrospective chart and ultrasound review of children with a diagnosis of isolated high grade (SFU grade 3 or 4) hydronephrosis was performed. This study also analyzed the impact on predictive ability of the PT obtained on an ultrasound obtained before 3 days of life compared to those in which the first ultrasound was obtained after 3 days of life. 91 infants (77 boys and 14 girls) met eligibility criteria (105 kidneys). The median age (IQR) at first ultrasound was 1.5 (1.0-15.0) days and 54.0 (27.5-123.0) days at the second ultrasound. DISCUSSION AND CONCLUSION: For the group overall, a smaller PT on both the first and second ultrasound was associated with increased risk of pyeloplasty, however, a PT obtained on an ultrasound prior to 3 days of life was not demonstrated to be predictive. Of note, PT was predictive in this same group of patients on their second ultrasound. A PT of <3 mm on an ultrasound obtained beyond 3 days of life was associated with higher risk of pyeloplasty. The PT ratio of hydronephrotic to normal contralateral kidney of the children who had their first ultrasound after 3 days of life was also significant in predicting the odds of having surgery. In addition, a decreasing PT between the first and second ultrasound was also identified as a risk factor for pyeloplasty.