Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.

MCL-1 is essential for promoting the survival of many normal cell lineages and confers survival and chemoresistance in cancer. Beyond apoptosis regulation, MCL-1 has been linked to modulating mitochondrial metabolism, but the mechanism(s) by which it does so are unclear. Here, we show in tissues and cells that MCL-1 supports essential steps in long-chain (but not short-chain) fatty acid ß-oxidation (FAO) through its binding to specific long-chain acyl-coenzyme A (CoA) synthetases of the ACSL family. ACSL1 binds to the BH3-binding hydrophobic groove of MCL-1 through a non-conventional BH3-domain. Perturbation of this interaction, via genetic loss of Mcl1, mutagenesis, or use of selective BH3-mimetic MCL-1 inhibitors, represses long-chain FAO in cells and in mouse livers and hearts. Our findings reveal how anti-apoptotic MCL-1 facilitates mitochondrial metabolism and indicate that disruption of this function may be associated with unanticipated cardiac toxicities of MCL-1 inhibitors in clinical trials.

Associative Visuomotor Learning Using Transcranial Magnetic Stimulation Induces Stimulus-Response Interference.

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by associative learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using TMS would result in stimulus-response associations that can impact future behavior. During a learning phase, we repeatedly paired the presentation of a specific color (but not other colors) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced-choice task where they had to categorize simple shapes and we studied whether the shapes' task-irrelevant color (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation. Although we were inspired by the Hebbian learning literature, future studies should investigate whether Hebbian or other learning processes were also what brought about this effect.

Effects of Ionic Interferents on Electrocatalytic Nitrate Reduction: Mechanistic Insight.

Nitrate, a prevalent water pollutant, poses substantial public health concerns and environmental risks. Electrochemical reduction of nitrate (eNO3RR) has emerged as an effective alternative to conventional biological treatments. While extensive lab work has focused on designing efficient electrocatalysts, implementation of eNO3RR in practical wastewater settings requires careful consideration of the effects of various constituents in real wastewater. In this critical review, we examine the interference of ionic species commonly encountered in electrocatalytic systems and universally present in wastewater, such as halogen ions, alkali metal cations, and other divalent/trivalent ions (Ca2+, Mg2+, HCO3-/CO32-, SO42-, and PO43-). Notably, we categorize and discuss the interfering mechanisms into four groups: (1) loss of active catalytic sites caused by competitive adsorption and precipitation, (2) electrostatic interactions in the electric double layer (EDL), including ion pairs and the shielding effect, (3) effects on the selectivity of N intermediates and final products (N2 or NH3), and (4) complications by the hydrogen evolution reaction (HER) and localized pH on the cathode surface. Finally, we summarize the competition among different mechanisms and propose future directions for a deeper mechanistic understanding of ionic impacts on eNO3RR.

Seasonal variation in the biological succession of marine diatoms over 316L stainless steel in a coastal environment of Chile.

Characterizing seasonal changes in diatom community profiles in coastal environments is scarce worldwide. Despite diatoms being prevalent in microfouling, their role in microbially influenced corrosion of metallic materials remains poorly understood. This study reports the effect of seasonal variations on the settlement of marine diatoms and corrosion of 316 L stainless steel surfaces exposed to Chilean coastal seawater. Electron microscopy imaging revealed a diverse assembly of diatoms, exhibiting pronounced differences at genus level between summer and winter seasons, with a significant delay in diatom settlement during winter. Electrochemical measurements indicated an active role of diatoms in increasing corrosion current during biofilm development. While the final diatom composition was similar irrespective of the season, the analyses of diatom assemblages over time differed, showing faster colonization when silicate and nitrate were available. This study lays the foundation for future research on the dominant season-specific genera of diatoms to unveil the microbial interactions that could contribute to corrosion and to evaluate their potential as bioindicators for alternative surveillance strategies.

A National Database Study on Racial Disparities in Route of Hysterectomy with a Surrogate Control for Uterine Size: A Proposed Quality Metric for Benign Indications.

STUDY OBJECTIVE: To investigate the association between race and route of hysterectomy among patients undergoing hysterectomy for abnormal uterine bleeding in the absence of uterine fibroid disease and excluding malignancy. DESIGN: A cross-sectional cohort study utilizing the Healthcare Cost and Utilization Project Nationwide Inpatient Sample and National Ambulatory Surgical databases to compare abdominal to minimally invasive route of hysterectomy. SETTING: Hospitals and hospital-affiliated ambulatory surgical centers participating in the Healthcare Cost and Utilization Project in 2019 PATIENTS: 75,838 patients who had undergone hysterectomy for abnormal uterine bleeding excluding uterine fibroids and malignancy. INTERVENTIONS: n/a MEASUREMENTS AND MAIN RESULTS: Of the 75,838 hysterectomies performed for abnormal uterine bleeding in the absence of uterine fibroids and malignancy, 10.1% were performed abdominally and 89.9% minimally invasively. After adjusting for confounders, Black patients were 38% more likely to undergo abdominal hysterectomy compared to White patients (OR 1.38, CI 1.12-1.70 p=0.002). Black race thus is independently associated with open surgery. CONCLUSION: Despite excluding uterine fibroids as a risk factor for an abdominal route of hysterectomy, Black race remained an independent predictor for abdominal versus minimally invasive hysterectomy and Black patients were found to undergo a disproportionately higher rate of abdominal hysterectomy compared to White patients.

A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment.

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment (N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19.

Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis.

BACKGROUND: Previous randomised controlled trials comparing bladder preservation with radical cystectomy for muscle-invasive bladder cancer closed due to insufficient accrual. Given that no further trials are foreseen, we aimed to use propensity scores to compare trimodality therapy (maximal transurethral resection of bladder tumour followed by concurrent chemoradiation) with radical cystectomy. METHODS: This retrospective analysis included 722 patients with clinical stage T2-T4N0M0 muscle-invasive urothelial carcinoma of the bladder (440 underwent radical cystectomy, 282 received trimodality therapy) who would have been eligible for both approaches, treated at three university centres in the USA and Canada between Jan 1, 2005, and Dec 31, 2017. All patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ. The 440 cases of radical cystectomy represent 29% of all radical cystectomies performed during the study period at the contributing institutions. The primary endpoint was metastasis-free survival. Secondary endpoints included overall survival, cancer-specific survival, and disease-free survival. Differences in survival outcomes by treatment were analysed using propensity scores incorporated in propensity score matching (PSM) using logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW). FINDINGS: In the PSM analysis, the 3:1 matched cohort comprised 1119 patients (837 radical cystectomy, 282 trimodality therapy). After matching, age (71·4 years [IQR 66·0-77·1] for radical cystectomy vs 71·6 years [64·0-78·9] for trimodality therapy), sex (213 [25%] vs 68 [24%] female; 624 [75%] vs 214 [76%] male), cT2 stage (755 [90%] vs 255 [90%]), presence of hydronephrosis (97 [12%] vs 27 [10%]), and receipt of neoadjuvant or adjuvant chemotherapy (492 [59%] vs 159 [56%]) were similar between groups. Median follow-up was 4·38 years (IQR 1·6-6·7) versus 4·88 years (2·8-7·7), respectively. 5-year metastasis-free survival was 74% (95% CI 70-78) for radical cystectomy and 75% (70-80) for trimodality therapy with IPTW and 74% (70-77) and 74% (68-79) with PSM. There was no difference in metastasis-free survival either with IPTW (subdistribution hazard ratio [SHR] 0·89 [95% CI 0·67-1·20]; p=0·40) or PSM (SHR 0·93 [0·71-1·24]; p=0·64). 5-year cancer-specific survival for radical cystectomy versus trimodality therapy was 81% (95% CI 77-85) versus 84% (79-89) with IPTW and 83% (80-86) versus 85% (80-89) with PSM. 5-year disease-free survival was 73% (95% CI 69-77) versus 74% (69-79) with IPTW and 76% (72-80) versus 76% (71-81) with PSM. There were no differences in cancer-specific survival (IPTW: SHR 0·72 [95% CI 0·50-1·04]; p=0·071; PSM: SHR 0·73 [0·52-1·02]; p=0·057) and disease-free survival (IPTW: SHR 0·87 [0·65-1·16]; p=0·35; PSM: SHR 0·88 [0·67-1·16]; p=0·37) between radical cystectomy and trimodality therapy. Overall survival favoured trimodality therapy (IPTW: 66% [95% CI 61-71] vs 73% [68-78]; hazard ratio [HR] 0·70 [95% CI 0·53-0·92]; p=0·010; PSM: 72% [69-75] vs 77% [72-81]; HR 0·75 [0·58-0·97]; p=0·0078). Outcomes for radical cystectomy and trimodality therapy were not statistically different among centres for cancer-specific survival and metastasis-free survival (p=0·22-0·90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3-4 in 194 (44%), and 114 (26%) node positive. The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2·5% (n=11). INTERPRETATION: This multi-institutional study provides the best evidence to date showing similar oncological outcomes between radical cystectomy and trimodality therapy for select patients with muscle-invasive bladder cancer. These results support that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all suitable candidates with muscle-invasive bladder cancer and not only to patients with significant comorbidities for whom surgery is not an option. FUNDING: Sinai Health Foundation, Princess Margaret Cancer Foundation, Massachusetts General Hospital.

Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.

Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+ activity in both sensory and non-sensory cells. Calcium signalling in neonatal OHCs can be modulated by oncomodulin (OCM, ß-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+ activity and afferent connectivity during development. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+ ) and Ocm knockout (Ocm-/- ) littermates, we found increased spontaneous Ca2+ activity and upregulation of purinergic receptors in OHCs from Ocm-/- cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibres on Ocm-/- OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+ signalling in the developing cochlea and the maturation of OHC afferent innervation. KEY POINTS: Cochlear outer hair cells (OHCs) exhibit spontaneous Ca2+ activity during a narrow period of neonatal development. OHC afferent maturation and connectivity requires spontaneous Ca2+ activity. Oncomodulin (OCM, ß-parvalbumin), an EF-hand calcium-binding protein, modulates Ca2+ signals in immature OHCs. Using transgenic mice that endogenously expressed a Ca2+ sensor, GCaMP6s, we found increased spontaneous Ca2+ activity and upregulated purinergic receptors in Ocm-/- OHCs. The maturation of afferent synapses in Ocm-/- OHCs was also delayed, leading to an upregulation of ribbon synapses and afferent fibres in Ocm-/- OHCs before hearing onset. We propose that OCM plays an important role in modulating Ca2+ activity, expression of Ca2+ channels and afferent innervation in developing OHCs.

Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Firefighter occupational factors and the risk of preterm birth: results from a survey of women firefighters in the USA.

OBJECTIVES: Previous research has suggested that women firefighters may have a greater risk of adverse reproductive outcomes compared with non-firefighting women. In this study, we investigated the association between firefighter occupational factors and risk of preterm birth. METHODS: This cross-sectional analysis of US firefighters surveyed in 2017 compared preterm birth among firefighters to non-firefighters using age-at-pregnancy-standardised prevalence ratios. Generalised estimating equations estimated relative risks and 95% CIs between firefighter occupational factors (career or volunteer, wildland status, shift schedule, fire responses, work restriction) and preterm birth risk. We adjusted for age-at-pregnancy, education, gravidity, BMI, and smoking and considered effect modification by age-at-pregnancy and career versus volunteer status. RESULTS: Among 934 women who reported 1356 live births, 12% were preterm (n=161). Preterm birth prevalence among firefighters was 1.41 times greater than non-firefighters (95% CI 1.18 to 1.68). Among wildland and combination wildland/structural firefighters, volunteers had 2.82 times the risk of preterm birth (95% CI 1.19 to 6.67) compared with career firefighters. Firefighters who started restricting their work in the 2nd trimester had a nonsignificant 0.67 times lower risk of preterm birth than those who started in the 3rd trimester or did not restrict work at all (95% CI 0.43 to 1.03). CONCLUSIONS: Firefighters may have greater risk of preterm birth than non-firefighters, which could be influenced by roles in the fire service and work restrictions taken.

Outcomes and management of pregnancy and puerperal group A streptococcal infections: A systematic review.

INTRODUCTION: Group A streptococcus (Streptococcus pyogenes) is one of the most lethal bacterial pathogens of humans, with increased risk of progression to septic shock and multiorgan failure in the pregnant population. The objective of this study is to systematically review the outcomes and management strategies for pregnancy and puerperal group A streptococcus infections in an effort to provide further guidance for prevention and treatment of a rare but lethal infection worldwide. MATERIAL AND METHODS: A comprehensive search using puerperium and streptococcus pyogenes terms was completed across several registered databases. A total of 902 articles investigating pregnancy and puerperal group A streptococcus infection were identified, with 40 studies fulfilling inclusion criteria of original research articles in humans published from 1990 onwards reporting four or more unique cases of group A streptococcus in pregnancy or postpartum. This study was registered in PROSPERO: CRD42020198983. RESULTS: A total of 1160 patients with pregnancy and puerperal group A streptococcus infection were identified. Most infections occurred postpartum (91.9%), with 4.7% reported antepartum and 0.6% intrapartum. Bacteremia was present in 49.0% of patients and endometritis in 45.9%. Puerperal sepsis was described in 28.2% of cases and progressed to streptococcal toxic shock syndrome in one-third of such cases. Overall, the case fatality ratio was 2.0%, with one-third of the deaths from antenatal cases including 3/22 (13.6%) cases of septic abortion and 10/46 (21.7%) antenatal cases of group A streptococcus infection. CONCLUSIONS: Group A streptococcus infection remains an important contributor to pregnancy and puerperal morbidity and mortality. Early recognition, diagnosis and aggressive management are important for favorable outcomes given the serious risk of sepsis and streptococcal toxic shock syndrome.

A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery.

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative Fi O2 was 0.30 (0.26-0.35 [0.20-0.59]) and 0.47 (0.44-0.51 [0.37-0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14-0.20), p < 0.001). Median time-weighted average intra-operative Fi O2 was 0.83 (0.80-0.85 [0.70-0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33-0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.

Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes.

Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l-1 , was compared with three inflammation groups: quartile 2 > 85 mg.l-1 to 140 mg.l-1 ; quartile 3 > 140 mg.l-1 to 200 mg.l-1 ; and quartile 4 > 200 mg.l-1 to 587 mg.l-1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated with increased risk of complications, poor quality of recovery and persistent disability or death up to 90 days after surgery.

How to use natural history collections to resurrect information on historical parasite abundances.

Many of the most contentious questions that concern the ecology of helminths could be resolved with data on helminth abundance over the past few decades or centuries, but unfortunately these data are rare. A new sub-discipline - the historical ecology of parasitism - is resurrecting long-term data on the abundance of parasites, an advancement facilitated by the use of biological natural history collections. Because the world's museums hold billions of suitable specimens collected over more than a century, these potential parasitological datasets are broad in scope and finely resolved in taxonomic, temporal and spatial dimensions. Here, we set out best practices for the extraction of parasitological information from natural history collections, including how to conceive of a project, how to select specimens, how to engage curators and receive permission for proposed projects, standard operating protocols for dissections and how to manage data. Our hope is that other helminthologists will use this paper as a reference to expand their own research programmes along the dimension of time.

Opportunity Neglect: An Aversion to Low-Probability Gains.

Seven preregistered studies (N = 2,890, adult participants) conducted in the field, in the lab, and online documented opportunity neglect: a tendency to reject opportunities with low probability of success even when they come with little or no objective cost (e.g., time, money, reputation). Participants rejected a low-probability opportunity in an everyday context (Study 1). Participants also rejected incentive-compatible gambles with positive expected value-for both goods (Study 2) and money (Studies 3-7)-even with no possibility of monetary loss and nontrivial rewards (e.g., a 1% chance at $99). Participants rejected low-probability opportunities more frequently than high-probability opportunities with equal expected value (Study 3). Although taking some real-life opportunities comes with costs, we show that people are even willing to incur costs to opt out of low-probability opportunities (Study 4). Opportunity neglect can be mitigated by highlighting that rejecting an opportunity is equivalent to choosing a zero probability of success (Studies 6-7).

Evaluating the Strength of Association of Human Papillomavirus Infection With Penile Carcinoma: A Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection that is strongly associated with cervical cancer. A link to penile cancers has been suggested by case series. We sought to assess the strength of the association between HPV infection and penile cancer by meta-analysis. METHODS: A literature search to identify population-based studies evaluating the risk of HPV infection with penile cancer was conducted via PubMed and Google Scholar databases through December 2020. Studies were included in the pooled analyses if they presented relative risk (RR) estimates comparing penile cancer cases with noncases by HPV exposure status. They were stratified by (1) type of HPV, (2) test used to determine past HPV infection, and (3) the penile cancer type. Pooled analyses were conducted for stratum with at least 2 independent studies using fixed-effects and random-effects models. RESULTS: Fourteen articles representing 9 study populations fit the inclusion criteria and were included in the pooled analysis. Based on these studies, the pooled RRs are 2.9 (95% confidence interval [CI], 1.7-5.0; n = 4 studies) for invasive penile cancer and seropositivity to HPV16 L1, 4.5 (95% CI, 1.3-15.5; n = 2) for seropositivity to HPV18, and 8.7 for anogenital warts (95% CI, 5.1-14.8; n = 5). For the 3 studies reporting invasive and in situ penile cancer, the risk was 7.6 for anogenital warts. CONCLUSIONS: The pooled RRs indicate up to a 4.5-fold increased risk between seropositivity for HPV infection and invasive penile cancer. This is much lower than associations seen between HPV and cervical cancer.

Evaluating the Meteorological Effects on the Urban Form-Air Quality Relationship Using Mobile Monitoring.

Predictive models based on mobile measurements have been increasingly used to understand the spatiotemporal variations of intraurban air quality. However, the effects of meteorological factors, which significantly affect the dispersion of air pollution, on the urban-form-air-quality relationship have not been understood on a granular level. We attempt to fill this gap by developing predictive models of particulate matter (PM) in the Bronx (New York City) using meteorological and urban form parameters. The granular PM data was collected by mobile low-cost sensors as the ground truth. To evaluate the effects of meteorological factors, we compared the performance of models using the urban form within fixed and wind-sensitive buffers, respectively. We find better predictive power in the wind-sensitive group (R = 0.85) for NC10 (number concentration for particles with diameters of 1 µm-10 µm) than the control group (R = 0.01), and modest improvements for PM2.5 (R = 0.84 for the wind sensitive group, R = 0.77 for the control group), indicating that incorporating meteorological factors improved the predictive power of our models. We also found that urban form factors account for 62.95% of feature importance for NC10 and 14.90% for PM2.5 (9.99% and 4.91% for 3-D and 2-D urban form factors, respectively) in our Random Forest models. It suggests the importance of incorporating urban form factors, especially for the uncommonly used 3-D characteristics, in estimating intraurban PM. Our method can be applied in other cities to better capture the influence of urban context on PM levels.

Effect of routine first-trimester combined screening for pre-eclampsia on small-for-gestational-age birth: secondary interrupted time series analysis.

OBJECTIVE: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome. METHODS: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA). RESULTS: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile. CONCLUSIONS: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Perceived discrimination and cognitive function among older Puerto Ricans in Boston: The mediating role of depression.

OBJECTIVES: To examine (1) the association between perceived discrimination, including everyday perceived discrimination and major lifetime perceived discrimination, and cognitive function and (2) the mediating role of depression between discrimination and cognitive function among older Puerto Ricans. METHODS: Data came from the Boston Puerto Rican Health Study, collected from 562 Puerto Ricans aged 60+. Structural Equation Modelling was used to examine the association between discrimination and cognitive function and the mediating effect of depression. RESULTS: Everyday perceived discrimination was negatively associated with cognitive function, which was fully mediated by depression. Major Lifetime perceived discrimination was not associated with cognitive function. CONCLUSIONS: The findings contribute new information regarding the impact of perceived discrimination on cognitive function among older Puerto Ricans and underscore the importance of assessing experiences of discrimination to prevent depression and cognitive decline in this population.

Adnexal torsion: a review of diagnosis and management strategies.

PURPOSE OF REVIEW: Adnexal torsion remains a diagnostic challenge heavily reliant on high clinical suspicion, with patient presentation and imaging used as adjuncts to aid in its diagnosis. This review summarizes diagnostic and management techniques of adnexal torsion to assist providers when encountering this surgical emergency. RECENT FINDINGS: Common findings of adnexal torsion include abdominal pain, nausea, vomiting, and adnexal mass or ovarian enlargement. An elevated neutrophil to lymphocyte ratio may be useful for diagnosis. A 'whirlpool' sign, 'follicular ring' sign, enlarged/edematous ovary, and absent Doppler flow to the ovary are highly suggestive of adnexal torsion. Intraoperative visual diagnosis of ovarian death is highly inaccurate, with only 18-20% of ovaries necrotic on pathological examination. Necrotic appearing ovaries have been shown to have follicular activity on ultrasound one year postoperatively. SUMMARY: Pelvic ultrasound remains the first-line imaging modality. In patients of reproductive age, we recommend performing detorsion with ovarian conservation, even in cases where the tissue appears necrotic, given poor intraoperative diagnostic rates of tissue death. Retention of ovarian function is also reliant on a timely diagnosis and intervention. We emphasize that the risk of ovarian damage/loss outweigh the risk of a diagnostic laparoscopy in patients of reproductive age.