In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

Cohort Study of Downgraded Misdemeanor Convictions and Subsequent Violent Crime: Differences by Defendant Race and Ethnicity.

Introduction: Criminal convictions may be imperfect markers of criminalized behavior, in part because of criminal legal system processes (e.g., plea bargaining). In this retrospective cohort study of individuals convicted of misdemeanors, authors compared the risk of subsequent criminal charges for a violent crime among those initially charged with a felony with that among those initially charged with only misdemeanors, overall and by defendant race and ethnicity. Methods: The study population included individuals aged ≥18 years who were convicted of a misdemeanor in Washington Superior Courts from January 1, 2015 to December 31, 2019. Those with and without initial felony charges were age/gender matched in a 4:1 ratio. The primary outcome was the first subsequent violent crime charge in Washington Superior Courts through December 31, 2020. Data were analyzed with Fine-Gray hazard models from June 2022 to November 2023. Results: There were 3,841 individuals with initial felony charges and 956 with initial misdemeanor charges only. Median follow-up was 2.4 years for both groups. During follow-up, there were 166 new violent crime charges. In multivariable models, White defendants with initial felony charges had a greater risk of subsequent violent crime charges (subdistribution hazard ratio=2.58; 95% CI=1.24, 5.36) than White defendants with initial misdemeanor charges only. Among Black and Hispanic/Latinx defendants, initial felony versus misdemeanor charges were not associated with subsequent violent crime charges (subdistribution hazard ratio=0.93; 95% CI=0.44, 1.97 among Black defendants; subdistribution hazard ratio=0.49; 95% CI=0.15, 1.57 among Hispanic/Latinx defendants). Conclusions: Findings suggest differential associations between downgrading of felony charges to misdemeanor convictions and future violent crime charges by defendant race and ethnicity, with implications for inequitable collateral consequences of criminal convictions.

A platform for predicting mechanism of action based on bacterial transcriptional responses identifies an unusual DNA gyrase inhibitor.

In the search for much-needed new antibacterial chemical matter, a myriad of compounds have been reported in academic and pharmaceutical screening endeavors. Only a small fraction of these, however, are characterized with respect to mechanism of action (MOA). Here, we describe a pipeline that categorizes transcriptional responses to antibiotics and provides hypotheses for MOA. 3D-printed imaging hardware PFIboxes) profiles responses of Escherichia coli promoter-GFP fusions to more than 100 antibiotics. Notably, metergoline, a semi-synthetic ergot alkaloid, mimics a DNA replication inhibitor. In vitro supercoiling assays confirm this prediction, and a potent analog thereof (MLEB-1934) inhibits growth at 0.25 µg/mL and is highly active against quinolone-resistant strains of methicillin-resistant Staphylococcus aureus. Spontaneous suppressor mutants map to a seldom explored allosteric binding pocket, suggesting a mechanism distinct from DNA gyrase inhibitors used in the clinic. In all, the work highlights the potential of this platform to rapidly assess MOA of new antibacterial compounds.

Firearm Ownership and Support for Political Violence in the United States.

Importance: Little is known about support for and willingness to engage in political violence in the United States. Such violence would likely involve firearms. Objective: To evaluate whether firearm owners' and nonowners' support for political violence differs and whether support among owners varies by type of firearms owned, recency of purchase, and frequency of carrying a loaded firearm in public. Design, Setting, and Participants: This cross-sectional nationally representative survey study was conducted from May 13 to June 2, 2022, among US adult members of the Ipsos KnowledgePanel, including an oversample of firearm owners. Exposure: Firearm ownership vs nonownership. Main Outcomes and Measures: Main outcomes concern (1) support for political violence, in general and to advance specific political objectives; (2) personal willingness to engage in political violence, by severity of violence and target population; and (3) perceived likelihood of firearm use in political violence. Outcomes are expressed as weighted proportions and adjusted prevalence differences, with P values adjusted for the false-discovery rate and reported as q values. Results: The analytic sample comprised 12 851 respondents: 5820 (45.3%) firearm owners, 6132 (47.7%) nonowners without firearms at home, and 899 (7.0%) nonowners with firearms at home. After weighting, 51.0% (95% CI, 49.9%-52.1%) were female, 8.5% (95% CI, 7.5%-9.5%) Hispanic, 9.1% (95% CI, 8.1%-10.2%) non-Hispanic Black, and 62.6% (95% CI, 61.5%-63.8%) non-Hispanic White; the mean (SD) age was 48.5 (18.0) years. Owners were more likely than nonowners without firearms at home to consider violence usually or always justified to advance at least 1 of 17 specific political objectives (owners: 38.8%; 95% CI, 37.3%-40.4%; nonowners: 29.8%; 95% CI, 28.5%-31.2%; adjusted difference, 6.5 percentage points; 95% CI, 4.5-9.3 percentage points; q < .001) but were not more willing to engage in political violence. Recent purchasers, owners who always or nearly always carry loaded firearms in public, and to a lesser extent, owners of assault-type rifles were more supportive of and willing to engage in political violence than other subgroups of firearm owners. Conclusions and Relevance: In this study of support for political violence in the United States, differences between firearm owners and nonowners without firearms at home were small to moderate when present. Differences were greater among subsets of owners than between owners and nonowners. These findings can guide risk-based prevention efforts.

Measuring interpersonal firearm violence: natural language processing methods to address limitations in criminal charge data.

OBJECTIVE: Firearm violence constitutes a public health crisis in the United States, but comprehensive data infrastructure is lacking to study this problem. To address this challenge, we used natural language processing (NLP) to classify court record documents from alleged violent crimes as firearm-related or non-firearm-related. MATERIALS AND METHODS: We accessed and digitized court records from the state of Washington (n = 1472). Human review established a gold standard label for firearm involvement (yes/no). We developed a key term search and trained supervised machine learning classifiers for this labeling task. Results were evaluated in a held-out test set. RESULTS: The decision tree performed best (F1 score: 0.82). The key term list had perfect recall (1.0) and a modest F1 score (0.65). DISCUSSION AND CONCLUSION: This case report highlights the accuracy, feasibility, and potential time-saved by using NLP to identify firearm involvement in alleged violent crimes based on digitized narratives from court documents.

Reporting and Description of Research Methodology in Studies Estimating Effects of Firearm Policies.

BACKGROUND: Evidence about which firearm policies work, to what extent, and for whom is hotly debated, perhaps partly because variation in research methodology has produced mixed and inconclusive effect estimates. We conducted a scoping review of firearm policy research in the health sciences in the United States, focusing on methodological considerations for causal inference. METHODS: We identified original, empirical articles indexed in PubMed from 1/1/2000-9/1/2021 that examined any of 18 pre-specified firearm policies. We extracted key study components, including policy type(s) examined, policy operationalization, outcomes, study setting and population, study approach and design, causal language, and whether and how authors acknowledged potential sources of bias. RESULTS: We screened 7733 articles and included 124. A plurality of studies used a legislative score as their primary exposure (n=39; 32%) and did not examine change in policies over time (n=47; 38%). Most examined firearm homicide (n=51; 41%) or firearm suicide (n=40; 32%) as outcomes. One-third adjusted for other firearm policies (n=41; 33%). Three studies (2%) explicitly mentioned that their goal was to estimate causal effects, but over half used language implying causality (n=72; 58%). Most acknowledged causal identification assumptions of temporality (n=91; 73%) and exchangeability (n=111; 90%); other assumptions were less often acknowledged. One-third of studies included bias analyses (n=42; 34%). CONCLUSIONS: We identified a range of methodologic approaches in firearm policy research in the health sciences. Acknowledging limitations of data availability and quality, we identify opportunities to improve causal inferences about and reporting on the effects of firearm policies on population health.

Co-Developing Theories of Change for Improved Community-Based Violence Intervention Evaluation.

BACKGROUND: Community-based violence intervention (CVI) programs are considered important strategies for preventing community violence and promoting health and safety. Mixed and inconclusive results from some prior CVI evaluations-and our general lack of understanding about the reasons for such varied findings-may be explained in part by misalignment of program theories of change and evaluation measures. Further, most prior evaluations have focused solely on deficit-based outcomes; this narrow focus is inconsistent with the premise of CVI and may fail to capture improvements in health and wellbeing that are on the hypothesized pathway from intervention to violence reduction. METHODS: This paper describes the process and results of co-developing a theory of change for community-based youth firearm violence intervention and prevention programs in Washington state through a community-researcher partnership. We followed a multi-step iterative process, involving 1) CVI program documentation review, 2) individual meetings, and 3) a day-long workshop. RESULTS: The theory of change included 6 key domains: 1) root causes, 2) promotive factors, 3) activities, 4) inter-mediate outcomes, 5) longer-term outcomes, and 6) multi-level context (youth/family, staff/organizational, community, and societal). Root causes were social and structural drivers of community violence. Promotive factors were assets and resources among the community, youth/their families, and community organizations that promote health and safety. Activities were supports and services the program provided to youth and their families, staff, and potentially the broader community. Inter-mediate and longer-term outcomes were the changes among youth, their families, staff, and the community that resulted from program activities. Inter-mediate outcomes may be felt within 6 months to 1 year and longer-term outcomes may be felt after 1-2 years and beyond. CONCLUSIONS: The theory of change we co-developed provides a common lens to conceptualize, compare, and evaluate CVI programs in Washington state and may support more rigorous and equity-centered evaluations.Study type: original investigation. LEVEL OF EVIDENCE: N/A.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

BACKGROUND: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity. METHODS: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction. RESULTS: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes. CONCLUSION: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05412004.

AlphaPept: a modern and open framework for MS-based proteomics.

In common with other omics technologies, mass spectrometry (MS)-based proteomics produces ever-increasing amounts of raw data, making efficient analysis a principal challenge. A plethora of different computational tools can process the MS data to derive peptide and protein identification and quantification. However, during the last years there has been dramatic progress in computer science, including collaboration tools that have transformed research and industry. To leverage these advances, we develop AlphaPept, a Python-based open-source framework for efficient processing of large high-resolution MS data sets. Numba for just-in-time compilation on CPU and GPU achieves hundred-fold speed improvements. AlphaPept uses the Python scientific stack of highly optimized packages, reducing the code base to domain-specific tasks while accessing the latest advances. We provide an easy on-ramp for community contributions through the concept of literate programming, implemented in Jupyter Notebooks. Large datasets can rapidly be processed as shown by the analysis of hundreds of proteomes in minutes per file, many-fold faster than acquisition. AlphaPept can be used to build automated processing pipelines with web-serving functionality and compatibility with downstream analysis tools. It provides easy access via one-click installation, a modular Python library for advanced users, and via an open GitHub repository for developers.

Nature's contribution to poverty alleviation, human wellbeing and the SDGs.

Millions of households globally rely on uncultivated ecosystems for their livelihoods. However, much of the understanding about the broader contribution of uncultivated ecosystems to human wellbeing is still based on a series of small-scale studies due to limited availability of large-scale datasets. We pooled together 11 comparable datasets comprising 232 settlements and 10,971 households in ten low-and middle-income countries, representing forest, savanna and coastal ecosystems to analyse how uncultivated nature contributes to multi-dimensional wellbeing and how benefits from nature are distributed between households. The resulting dataset integrates secondary data on rural livelihoods, multidimensional human wellbeing, household demographics, resource tenure and social-ecological context, primarily drawing on nine existing household surveys and their associated contextual information together with selected variables, such as travel time to cities, population density, local area GDP and land use and land cover from existing global datasets. This integrated dataset has been archived with ReShare (UK Data Service) and will be useful for further analyses on nature-wellbeing relationships on its own or in combination with similar datasets.

Social and economic determinants of drug overdose deaths: a systematic review of spatial relationships.

PURPOSE: To synthesize the available evidence on the extent to which area-level socioeconomic conditions are associated with drug overdose deaths in the United States. METHODS: We performed a systematic review (in MEDLINE, EMBASE, PsychINFO, Web of Science, EconLit) for papers published prior to July 2022. Eligible studies quantitatively estimated the association between an area-level measure of socioeconomic conditions and drug overdose deaths in the US, and were published in English. We assessed study quality using the Effective Public Health Practice Project Quality Assessment Tool. The protocol was preregistered at Prospero (CRD42019121317). RESULTS: We identified 28 studies that estimated area-level effects of socioeconomic conditions on drug overdose deaths in the US. Studies were scored as having moderate to serious risk of bias attributed to both confounding and in analysis. Socioeconomic conditions and drug overdose death rates were moderately associated, and this was a consistent finding across a large number of measures and differences in study designs (e.g., cross-sectional versus longitudinal), years of data analyzed, and primary unit of analysis (e.g., ZIP code, county, state). CONCLUSIONS: This review highlights the evidence for area-level socioeconomic conditions are an important factor underlying the geospatial distribution of drug overdose deaths in the US and the need to understand the mechanisms underlying these associations to inform future policy recommendations. The current evidence base suggests that, at least in the United States, employment, income, and poverty interventions may be effective targets for preventing drug overdose mortality rates.

Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space.

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling.

Organized abandonment under racial capitalism: Measuring accountable actors of structural racism for public health research and action.

Understanding the shifting nature of structural racism historically and across institutions is vital for effective action towards racial health equity. While public health research on structural racism is rapidly increasing, most studies are missing the interdependence of policies and institutional practices over time that shape power imbalances and lead to entrenched health inequities. Here, we discuss Ruth Wilson Gilmore's concept of organized abandonment - the intentional disinvestment in communities which, in turn, creates opportunities for extraction, revenue generation, and carceral enforcement to fill the cracks of a compromised social infrastructure - to encourage action-oriented public health research that is grounded in history and an understanding of racial capitalism. We present a case example using publicly-available data on redlining, gentrification and policing in Seattle, Washington. We mapped the intersections of redlining and gentrification and estimated their neighborhood-level association with police activity using Bayesian spatial Poisson regression models. We found that histories of racist housing policies like redlining and processes of gentrification are interdependent and shape contemporary neighborhood racial and economic segregation and police activity. Compared to structurally advantaged neighborhoods, police stops were higher in neighborhoods that were 1) historically disinvested (i.e. redlined) and remain low-income and structurally disadvantaged and 2) formerly industrial and business districts that were not redlined and are now gentrified. Notably, we found that policing practices were significantly more intensive in neighborhoods that were both high redlined and gentrified. Together, these findings illustrate how the place-based racialized processes of dispossession, displacement and policing are deeply intertwined to maintain racial capitalism. Our findings also highlight the importance of examining multiple racialized processes simultaneously to fill critical gaps in the existing literature that are necessary for sustainable solutions to address structural racism.

First-in-Human Evaluation of Site-Specifically Labeled 89Zr-Pertuzumab in Patients with HER2-Positive Breast Cancer.

Radioimmunoconjugates targeting human epidermal growth factor receptor 2 (HER2) have shown potential to noninvasively visualize HER2-positive tumors. However, the stochastic approach that has been traditionally used to radiolabel these antibodies yields poorly defined and heterogeneous products with suboptimal in vivo performance. Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry of 89Zr-site-specific (ss)-pertuzumab PET, a site-specifically labeled radioimmunoconjugate designed to circumvent the limitations of random stochastic lysine labeling. Methods: Six patients with HER2-positive metastatic breast cancer were enrolled in a prospective clinical trial. Pertuzumab was site-specifically modified with desferrioxamine (DFO) via a novel chemoenzymatic strategy and subsequently labeled with 89Zr. Patients were administered 74 MBq of 89Zr-ss-pertuzumab in 20 mg of total antibody intravenously and underwent PET/CT at 1 d, 3-4 d, and 5-8 d after injection. PET imaging, whole-body probe counts, and blood draws were performed to assess the pharmacokinetics, biodistribution, and dosimetry. Results: 89Zr-ss-pertuzumab PET/CT was used to assess HER2 status and heterogeneity to guide biopsy and decide the next line of treatment at progression. The radioimmunoconjugate was able to detect known sites of malignancy, suggesting that these tumor lesions were HER2-positive. The optimal imaging time point was 5-8 d after administration, and no toxicities were observed. Dosimetry estimates from OLINDA showed that the organs receiving the highest doses (mean ± SD) were kidney (1.8 ± 0.5 mGy/MBq), liver (1.7 ± 0.3 mGy/MBq), and heart wall (1.2 ± 0.1 mGy/MBq). The average effective dose for 89Zr-ss-pertuzumab was 0.54 ± 0.03 mSv/MBq, which was comparable to both stochastically lysine-labeled 89Zr-DFO-pertuzumab and 89Zr-DFO-trastuzumab. One patient underwent PET/CT with both 89Zr-ss-pertuzumab and 89Zr-DFO-pertuzumab 1 mo apart, with 89Zr-ss-pertuzumab demonstrating improved lesion detection and higher tracer avidity. Conclusion: This study demonstrated the safety, dosimetry, and potential clinical applications of 89Zr-ss-pertuzumab PET/CT. 89Zr-ss-pertuzumab may detect more lesions than 89Zr-DFO-pertuzumab. Potential clinical applications include real-time evaluation of HER2 status to guide biopsy and assist in treatment decisions.

LiOH Decomposition by NiO/ZrO2 in Li-Air Battery: Chemical Imaging with Operando Synchrotron Diffraction and Correlative Neutron/X-Ray Computed-Tomography Analysis.

Li-air batteries attract significant attention due to their highest theoretical energy density among all existing energy storage technologies. Currently, challenges related to extending lifetime and long-term stability limit their practical application. To overcome these issues and enhance the total capacity of Li-air batteries, this study introduces an innovative approach with NiO/ZrO2 catalysts. Operando advanced chemical imaging with micrometer spatial resolution unveils that NiO/ZrO2 catalysts substantially change the kinetics of crystalline lithium hydroxide (LiOH) formation and facilitate its rapid decomposition with heterogeneous distribution. Moreover, ex situ combined neutron and X-ray computed tomography (CT) analysis, provide evidence of distinct lithium phases homogeneously distributed in the presence of NiO/ZrO2 . These findings underscore the material's superior physico-chemical and electronic properties, with more efficient oxygen diffusion and indications of lower obstruction to its active sites, avoiding clogging in the active electrode, a common cause of capacity loss. Electrochemical tests conducted at high current density demonstrated a significant kinetic enhancement of the oxygen reduction and evolution reactions, resulting in improved charge and discharge processes with low overpotential. This pioneering approach using NiO/ZrO2 catalysts represents a step toward on developing the full potential of Li-air batteries as high-energy-density energy storage systems.

Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

Sensing in Sacral Neuromodulation: A Feasibility Study in Subjects With Urinary Incontinence and Retention.

OBJECTIVES: Sacral neuromodulation (SNM) therapy standard of care relies on visual-motor responses and patient-reported sensory responses in deciding optimized lead placement and programming. Automatic detection of stimulation responses could offer a simple, consistent indicator for optimizing SNM. The purpose of this study was to measure and characterize sacral evoked responses (SERs) resulting from sacral nerve stimulation using a commercial, tined SNM lead. MATERIALS AND METHODS: A custom external research system with stimulation and sensing hardware was connected to the percutaneous extension of an implanted lead during a staged (tined lead) evaluation for SNM. The system collected SER recordings across a range of prespecified stimulation settings (electrode configuration combinations for bipolar stimulation and bipolar sensing) during intraoperative and postoperative sessions in 21 subjects with overactive bladder (OAB) and nonobstructive urinary retention (NOUR). Motor and sensory thresholds were collected during the same sessions. RESULTS: SERs were detected in all 21 subjects. SER morphology (number of peaks, magnitude, and timing) varied across electrode configurations within and across subjects. Among subjects and electrode configurations tested, recordings contained SERs at motor threshold and/or sensory threshold in 75% to 80% of subjects. CONCLUSIONS: This study confirmed that implanted SNM leads can be used to directly record SERs elicited by stimulation in subjects with OAB and NOUR. SERs were readily detectable at typical SNM stimulation settings and procedural time points. Using these SERs as possible objective measures of SNM response has the capability to automate patient-specific SNM therapy, potentially providing consistent lead placement, programming, and/or closed-loop therapy.

Variables affecting surgeons' use of, and preferences for, instrumentation in veterinary laparoscopy.

OBJECTIVE: To investigate the impact of variables on use and preference of common laparoscopic instruments. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 years or more laparoscopic experience. METHODS: Electronic survey distributed via specialty group LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, preferences, and surgical practice data. Statistical analysis was performed using Fishers exact, ANOVA, Tukey Kramer honestly significant difference (HSD) test, linear regression, and logistic regression. RESULTS: Ninety-eight of 140 respondents answered instrument-related questions and the completion rate of these questions was 76%: 48% of females and 49% of males responded to the survey. The median glove size of respondents was size 7 (range, 5.5 to 8.5). Closing laparoscopic Babcock forceps (p = .018), rotating cup biopsy forceps (p = .003), and manipulating endoscopic staplers (p < .001) were more difficult for surgeons with smaller glove sizes. The median difficulty score for the endoscopic stapler was 4/10 and the median percentage of time this was found difficult was 25%. Reusable instruments were preferred over disposable single-use instruments. The pistol grip was preferred for grasping and retracting (54/98, 55%) and fine dissection (46/96, 48%), while the axial grip was preferred for suturing and knot tying (61/98, 62%). CONCLUSION: Surgeons with smaller glove sizes (<6.5) experience more difficulty when using common laparoscopic instruments. The endoscopic stapler was the most difficult to use. CLINICAL SIGNIFICANCE: When purchasing laparoscopic instrumentation, surgeons should review all available options in handle size and design to improve ergonomics during minimally invasive procedures.