Proteolysis of tau by granzyme A in tauopathies generates fragments that are aggregation prone.

Tauopathies, including Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy, are characterised by the aggregation of tau into insoluble neurofibrillary tangles in the brain. Tau is subject to a range of post-translational modifications, including proteolysis, that can promote its aggregation. Neuroinflammation is a hallmark of tauopathies and evidence is growing for a role of CD8+ T cells in disease pathogenesis. CD8+ T cells release granzyme proteases but what role these proteases play in neuronal dysfunction is currently lacking. Here, we identified that granzyme A (GzmA) is present in brain tissue and proteolytically cleaves tau. Mass spectrometric analysis of tau fragments produced on digestion of tau with GzmA identified three cleavage sites at R194-S195, R209-S210 and K240-S241. Mutation of the critical Arg or Lys residues at the cleavage sites in tau or chemical inhibition of GzmA blocked the proteolysis of tau by GzmA. Development of a semi-targeted mass spectrometry approach identified peptides in tauopathy brain tissue corresponding to proteolysis by GzmA at R209-S210 and K240-S241 in tau. When expressed in cells the GzmA-cleaved C-terminal fragments of tau were highly phosphorylated and aggregated upon incubation of the cells with tauopathy brain seed. The C-terminal fragment tau195-441 was able to transfer between cells and promote aggregation of tau in acceptor cells, indicating the propensity for such tau fragments to propagate between cells. Collectively, these results raise the possibility that GzmA, released from infiltrating cytotoxic CD8+ T cells, proteolytically cleaves tau into fragments that may contribute to its pathological properties in tauopathies.

Location and function of TDP-43 in platelets, alterations in neurodegenerative diseases and arising considerations for current plasma biobank protocols.

The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples. Surprisingly, implementation of these assays demonstrated that biobank-archived plasma samples yielded considerable heterogeneity in TDP-43 levels. Importantly, subsequent investigation attributed these differences to variable platelet recovery. Fractionations of fresh blood revealed that ≥ 95% of the TDP-43 in platelet-containing plasma was compartmentalized within the platelet cytosol. We reasoned that this highly concentrated source of TDP-43 comprised an interesting substrate for biochemical analyses. Additional characterization of platelets revealed the presence of the disease-associated phosphoserine 409/410 TDP-43 proteoform and many neuron- and astrocyte-expressed TDP-43 mRNA targets. Considering these striking similarities, we propose that TDP-43 may serve analogous functional roles in platelets and synapses, and that the study of platelet TDP-43 might provide a window into disease-related TDP-43 dyshomeostasis in the central nervous system.

Ecosystem engineers enhance the multifunctionality of an urban novel ecosystem: Population persistence and ecosystem resilience since the 1980s.

In degraded urban habitats, nature-based solutions aim to enhance ecosystem functioning and service provision. Bivalves are increasingly reintroduced to urban environments to enhance water quality through biofiltration, yet their long-term sustainability remains uncertain. Following the restoration of the disused South Docks in Liverpool in the 1980s, natural colonization of mussels rapidly improved dock-basin water quality and supported diverse taxa, including other filter feeders. While the initial colonization phase has been well documented, there has been limited published research since the mid-1990s, despite ongoing routine water quality monitoring. Here, we assessed the long-term persistence of mussel populations, their associated biodiversity, and physico-chemical parameters of the water in Queens and Albert Docks by comparing historical (1980s to 1990s) and contemporary data from follow-up surveys (2012,2022). Following an initial period of poor water quality (high contamination and turbidity, low oxygen), the natural colonization of mussels from Albert Dock in 1988 extended throughout the South Docks. By the mid-1990s, the environment of the South Docks and its mussel populations had stabilized. The dock walls were dominated by mussels which provided important complex secondary substrate for invertebrates and macroalgae. Surveys conducted in 2012 and 2022 confirmed the continued dominance of mussels and estimates of mussel biofiltration rates confirm that mussels are continuing to contribute to maintaining water quality. A decline in salinity was observed in both docks in 2022, with evidence of recovery. While these ecosystems appear relatively stable, careful management of the hydrological regime is crucial to ensuring the persistence of mussels and resilient ecosystem service provision through biofiltration.

Using geographic effect measure modification to examine socioeconomic-related surface temperature disparities in New York City.

BACKGROUND: Lower socioeconomic (SES) communities are more likely to be situated in urban heat islands and have higher heat exposures than their higher SES counterparts, and this inequality is expected to intensify due to climate change. OBJECTIVES: To examine the relationship between surface temperatures and SES in New York City (NYC) by employing a novel analytical approach. Through incorporating modifiable features, this study aims to identify potential locations where mitigation interventions can be implemented to reduce heat disparities associated with SES. METHODS: Using the 2013-2017 American Community Survey, U.S Landsat-8 Analysis Ready Data surface temperatures (measured on 8/12/2016), and the NYC Land Cover Dataset at the census tract level (2098 tracts), this study examines the association between two components of tract-level SES (percentage of individuals living below the poverty line and the percentage of individuals without a high school degree) and summer day surface temperature in NYC. First, we examine this association with an unrestricted NYC linear regression, examining the city-wide association between the two SES facets and summer surface temperature, with additional models adjusting for altitude, shoreline, and nature-cover. Then, we assess geographic effect measure modification by employing the same models to three supplemental regression model strategies (borough-restricted and community district-restricted linear regressions, and geographically weighted regression (GWR)) that examined associations within smaller intra-city areas. RESULTS: All regression strategies identified areas where lower neighborhood SES composition is associated with higher summer day surface temperatures. The unrestricted NYC regressions revealed widespread disparities, while the borough-restricted and community district-restricted regressions identified specific political boundaries within which these disparities existed. The GWR, addressing spatial autocorrelation, identified significant socioeconomic heat disparities in locations such as northwest Bronx, central Brooklyn, and uptown Manhattan. These findings underscore the need for targeted policies and community interventions, including equitable urban planning and cooling strategies, to mitigate heat exposure in vulnerable neighborhoods. IMPACT STATEMENT: This study redefines previous research on urban socioeconomic disparities in heat exposure by investigating both modifiable (nature cover) and non-modifiable (altitude and shoreline) built environment factors affecting local temperatures at the census tract level in New York City. Through a novel analytical approach, the research aims to highlight intervention opportunities to mitigate heat disparities related to socioeconomic status. By examining the association between surface temperatures and socioeconomic status, as well as investigating different geographic and governmental scales, this study offers actionable insights for policymakers and community members to address heat exposure inequalities effectively across different administrative boundaries. The objective is to pinpoint potential sites for reducing socioeconomic heat exposure disparities at various geographic and political levels.

Effects of Air Pollution on Respiratory Events and Pain Crises among Children with Sickle Cell Disease in New York City.

RATIONALE: The disease burden of sickle cell disease (SCD) is highest among U.S. Black and Hispanic populations, who are often disproportionately represented in communities with poor air quality. There is limited data on the effects of air pollution exposure and social environmental factors on health outcomes in children with SCD. OBJECTIVES: The objective of our study was to examine the associations between air pollution exposure and acute respiratory and vaso-occlusive pain crises (VOCs), and further study the associations stratifying by asthma status and neighborhood disadvantages. METHODS: We conducted a retrospective study collecting data on outpatient sick and ED visits, and hospital admissions for respiratory events (i.e., respiratory tract infections, asthma exacerbation, acute chest syndrome), and hospitalizations for VOCs among children with SCD in a tertiary care center in New York City (NYC) from 2015-2018. Modeled data from the NYC Community Air Survey data using home addresses estimated street-level, annual-average exposure to air pollution (i.e., black carbon (BC), fine particulate matter (PM2.5), and nitrogen dioxide (NO2)). The area deprivation index (ADI): continuous national ranking percentile (1-100) was used, representing a composite index for neighborhood-level social disadvantage. We further dichotomized study participants at the upper tertile (high vs. low ADI). Multivariable Poisson regression in generalized estimating equation (GEE) models were used to estimate relative risks (RR), after adjusting for potential covariates. RESULTS: A total of 114 children with SCD were included in this study and had between 1-4 annual repeated measures of annual average air pollutants over a total of 425 visits. Overall, there were no significant associations between air pollution levels and acute respiratory and VOCs among children with SCD and when stratified by asthma status. We found significant interactions between air pollution levels and the continuous ADI variable on respiratory outpatient and frequent respiratory outpatient/ED visits (p<0.1). When stratified by high ADI, increased exposure to PM2.5 was significantly associated with more frequent respiratory outpatient/ED visits among children residing in higher ADI neighborhoods (RR (95% CI)= 1.13 (1.01, 1.27), p<0.05), but not among those in lower ADI neighborhoods. Increased exposure to NO2 was associated with more outpatient respiratory events for children in high ADI neighborhoods (RR (95%CI= 2.74 (1.24, 6.08), p<0.05), compared with low ADI neighborhoods. CONCLUSIONS: Air pollution exposures increased respiratory complications among children with SCD living in deprived neighborhoods.

Neighborhood economic vulnerability as a predictor for patterns of care and outcomes for patients with uterine cancer.

OBJECTIVE: To quantify the effect of neighborhood socioeconomic vulnerability as it relates to racial disparity in uterine cancer treatment and survival. METHODS: Patients with a diagnosis of uterine cancer who underwent hysterectomy in New York State from 2004 to 2017 were included in this retrospective cohort study. Neighborhood socioeconomic vulnerability as quantified by the Area Deprivation Index was calculated. Primary outcome was guideline adherent treatment; secondary outcome was 5 year overall survival. RESULTS: A total of 34,356 patients were included in the final cohort. Residence within a vulnerable neighborhood was associated with a lower likelihood of receiving appropriate adjuvant chemotherapy (59.7% vs 75.7% with aRR = 0.81; 95% CI, 0.77-0.86) and timely surgery (63.7% vs. 74.5% with aRR = 0.85; 95% CI, 0.82-0.87). All-cause mortality was 24% higher for those who resided in vulnerable neighborhoods compared to affluent neighborhoods (aHR = 1.24; 95% CI, 1.16-1.32). The greatest Black/White racial disparity in 5 year overall survival was seen in the most affluent neighborhoods at 18.6%, with survival being 79.8% for White patients and 61.2% for Black patients (aHR 1.31; 95% CI 1.14-1.51). For patients with advanced stage disease, this disparity was driven by improved survival for White patients with increasing neighborhood affluence but no change in survival for Black patients. On adjusted analysis controlling for age, comorbidities, insurance, tumor histology, stage, and grade, the disparity remained widest in the most affluent neighborhoods in NYC (aHR = 1.59; 95%CI 1.26-1.2.01). CONCLUSIONS: Neighborhood socioeconomic vulnerability is associated with poor outcomes for patients with uterine cancer. The greatest Black/White survival disparities are in the wealthiest neighborhoods. Neighborhood affluence may not affect survival of Black patients with advanced stage endometrial cancer.

Serratus anterior plane block improves pain and incentive spirometry volumes in trauma patients with multiple rib fractures: a prospective cohort study.

Background: Rib fractures are common injuries associated with considerable morbidity, long-term disability, and mortality. Early, adequate analgesia is important to mitigate complications such as pneumonia and respiratory failure. Regional anesthesia has been proposed for rib fracture pain control due to its superior side effect profile compared with systemic analgesia. Our objective was to evaluate the effect of emergency physician-performed, ultrasound-guided serratus anterior plane block (SAPB) on pain and respiratory function in emergency department patients with multiple acute rib fractures. Methods: This was a prospective observational cohort study of adult patients at a level 1 trauma center who had two or more acute unilateral rib fractures. Eligible patients received a SAPB if an emergency physician trained in the procedure was available at the time of diagnosis. Primary outcomes were the absolute change in pain scores and percent change in expected incentive spirometry volumes from baseline to 3 hours after rib fracture diagnosis. Results: 38 patients met eligibility criteria, 15 received the SAPB and 23 did not. The SAPB group had a greater decrease in pain scores at 3 hours (-3.7 vs. -0.9; p=0.003) compared with the non-SAPB group. The SAPB group also had an 11% (CI 1.5% to 17%) increase in percent expected spirometry volumes at 3 hours which was significantly better than the non-SAPB group, which had a -3% (CI -9.1% to 2.7%) decrease (p=0.008). Conclusion: Patients with rib fractures who received SAPB as part of a multimodal pain control strategy had a greater improvement in pain and respiratory function compared with those who did not. Larger trials are indicated to assess the generalizability of these initial findings.

Disadvantaged groups have greater spatial access to pharmacies in New York state.

BACKGROUND: The accessibility of pharmacies has been associated with overall health and wellbeing. Past studies have suggested that low income and racial minority communities are underserved by pharmacies. However, the literature is inconsistent in finding links between area-level income or racial and ethnic composition and access to pharmacies. Here we aim to assess area-level spatial access to pharmacies across New York State (NYS), hypothesizing that Census Tracts with higher poverty rates and higher percentages of Black and Hispanic residents would have lower spatial access. METHODS: The population weighted mean shortest road network distance (PWMSD) to a pharmacy in 2018 was calculated for each Census Tract in NYS. This statistic was calculated from the shortest road network distance to a pharmacy from the centroid of each Census block within a tract, with the mean across census blocks weighted by the population of the census block. Cross-sectional analyses were conducted to assess links between Tract-level socio demographic characteristics and Tract-level PWMSD to a pharmacy. RESULTS: Overall the mean PWMSD to a pharmacy across Census tracts in NYS was 2.07 Km (SD = 3.35, median 0.85 Km). Shorter PWMSD to a pharmacy were associated with higher Tract-level % poverty, % Black/African American (AA) residents, and % Hispanic/Latino residents and with lower Tract-level % of residents with a college degree. Compared to tracts in the lowest quartile of % Black/AA residents, tracts in the highest quartile had a 70.7% (95% CI 68.3-72.9%) shorter PWMSD to a pharmacy. Similarly, tracts in the highest quartile of % poverty had a 61.3% (95% CI 58.0-64.4%) shorter PWMSD to a pharmacy than tracts in the lowest quartile. CONCLUSION: The analyses show that tracts in NYS with higher racial and ethnic minority populations and higher poverty rates have higher spatial access to pharmacies.

Chemical Profiles Differ between Communal Breeding Groups in a Highly Social Bird.

AbstractGregarious species must distinguish group members from nongroup members. Olfaction is important for group recognition in social insects and mammals but rarely studied in birds, despite birds using olfaction in social contexts from species discrimination to kin recognition. Olfactory group recognition requires that groups have a signature odor, so we tested for preen oil and feather chemical similarity in group-living smooth-billed anis (Crotophaga ani). Physiology affects body chemistry, so we also tested for an effect of egg-laying competition, as a proxy for reproductive status, on female chemical similarity. Finally, the fermentation hypothesis for chemical recognition posits that host-associated microbes affect host odor, so we tested for covariation between chemicals and microbiota. Group members were more chemically similar across both body regions. We found no chemical differences between sexes, but females in groups with less egg-laying competition had more similar preen oil, suggesting that preen oil contains information about reproductive status. There was no overall covariation between chemicals and microbes; instead, subsets of microbes could mediate olfactory cues in birds. Preen oil and feather chemicals showed little overlap and may contain different information. This is the first demonstration of group chemical signatures in birds, a finding of particular interest given that smooth-billed anis live in nonkin breeding groups. Behavioral experiments are needed to test whether anis can distinguish group members from nongroup members using odor cues.

Examining racial and ethnic heat exposure disparities in New York City (NYC) across different spatial and political scales through geographic effect measure modification.

Structural racism in the United States has resulted in neighborhoods with higher proportions of non-Hispanic Black (Black) or Hispanic/Latine residents having more features that intensify, and less that cool, the local-heat environment. This study identifies areas of New York City (NYC) where racial/ethnic heat exposure disparities are concentrated. We analyzed data from the 2013-2017 American Community Survey, U.S Landsat-8 Analysis Ready Data on summer surface temperatures, and NYC Land Cover Dataset at the census tract-level (n = 2098). Four cross-sectional regression modeling strategies were used to estimate the overall City-wide association, and associations across smaller intra-city areas, between tract-level percent of Black and percent Hispanic/Latine residents and summer day surface temperature, adjusting for altitude, shoreline, and nature-cover: overall NYC linear, borough-specific linear, Community District-specific linear, and geographically weighted regression models. All three linear regressions identified associations between neighborhood racial and ethnic composition and summer day surface temperatures. The geographically weighted regression models, which address the issue of spatial autocorrelation, identified specific locations (such as northwest Bronx, central Brooklyn, and uptown Manhattan) within which racial and ethnic disparities for heat exposures are concentrated. Through examining the overall effects and geographic effect measure modification across spatial scales, the results of this study identify specific geographic areas for intervention to mitigate heat exposure disparities experienced by Black and Hispanic/Latine NYC residents.

Military accession guidelines: An allergy focus.

Medical evaluation for military applicants is an intricate process that requires an understanding of the terminology, standards, and guidelines. Allergy providers are often called to provide medical evaluations for patients who desire to join the military services. Without understanding the complexities and nuances of military medical evaluations, a provider may delay or not be able to assist their patient in obtaining the desired goal of joining the services. This article reviews the terminology of military medical evaluations and the guidelines and processes for these evaluations. We also focus our discussion on common allergic conditions that may be disqualifying for service and provide expert opinions of the subtleties of these conditions to provide the allergist with a practical approach to medical evaluations. Finally, we provide a list of resources that are accessible to any provider engaged in military medical evaluations for accessions.

Ofatumumab Desensitization Protocol: A Case of Refractory Immune Thrombocytopenic Purpura.

Chronic immune thrombocytopenic purpura (ITP) is an acquired hematologic condition that involves immune-mediated platelet destruction with resultant bleeding of variable severity. Refractory ITP occurs when patients fail to tolerate and/or respond to multiple treatment modalities. In this case, we examine the clinical course of a 39-year-old female with refractory ITP and discuss how we navigated a multitude of challenges by adapting an established desensitization protocol to meet our patient's needs. To our knowledge, we describe the first successful desensitization to ofatumumab for use in ITP in the current literature.

Long-Term Exposure to Walkable Residential Neighborhoods and Risk of Obesity-Related Cancer in the New York University Women's Health Study (NYUWHS).

BACKGROUND: Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES: We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS: The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: Residing in neighborhoods with a higher walkability level was associated with a reduced risk of overall and site-specific obesity-related cancers. The hazards ratios associated with a 1-standard deviation increase in average annual neighborhood walkability were 0.88 (95% CI: 0.85, 0.93) for overall obesity-related cancer, 0.89 (95% CI: 0.84, 0.95) for postmenopausal breast cancer, 0.82 (95% CI: 0.68, 0.99) for ovarian cancer, 0.87 (95% CI: 0.76, 0.99) for endometrial cancer, and 0.68 (95% CI: 0.49, 0.94) for multiple myeloma, adjusting for potential confounders at both the individual and neighborhood level. The association between neighborhood walkability and risk of overall obesity-related cancer was stronger among women living in neighborhoods with higher levels of poverty compared with women living in areas with lower poverty levels (pInteraction=0.006). DISCUSSION: Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.

Age-Dependent Increase in Tau Phosphorylation at Serine 396 in Huntington's Disease Prefrontal Cortex.

BACKGROUND: To date, it is still controversial whether tau phosphorylation plays a role in Huntington's disease (HD), as previous studies demonstrated either no alterations or increases in phosphorylated tau (pTau) in HD postmortem brain and mouse models. OBJECTIVE: The goal of this study was to determine whether total tau and pTau levels are altered in HD. METHODS: Immunohistochemistry, cellular fractionations, and western blots were used to measure total tau and pTau levels in a large cohort of HD and control postmortem prefrontal cortex (PFC). Furthermore, western blots were performed to assess tau, and pTau levels in HD and control isogenic embryonic stem cell (ESC)-derived cortical neurons and neuronal stem cells (NSCs). Similarly, western blots were used to assess tau and pTau levels in HttQ111 and transgenic R6/2 mice. Lastly, total tau levels were assessed in HD and healthy control plasma using Quanterix Simoa assay. RESULTS: Our results revealed that, while there was no difference in total tau or pTau levels in HD PFC compared to controls, the levels of tau phosphorylated at S396 were increased in PFC samples from HD patients 60 years or older at time of death. Additionally, tau and pTau levels were not changed in HD ESC-derived cortical neurons and NSCs. Similarly, total tau or pTau levels were not altered in HttQ111 and transgenic R6/2 mice compared to wild-type littermates. Lastly, tau levels were not changed in plasma from a small cohort of HD patients compared to controls. CONCLUSIONS: Together these findings demonstrate that pTau-S396 levels increase significantly with age in HD PFC.

Advanced Ultrasonic Inspection of Thick-Section Composite Structures for In-Field Asset Maintenance.

An investigation into the inspection capabilities of in-field advanced ultrasound detection for use on ultra-thick (20 to 100 mm) glass fibre-reinforced polyester composites is presented. Plates were manufactured using custom moulding techniques, such that delamination flaws were created at calibrated depths. The full matrix capture technique with an on-board total focussing method was used to detect flaws scanned by a 0.5 MHz linear array probe. Flaw through-thickness dimensions were altered to assess the threshold for crack face separation at which delaminations could be identified. Furthermore, part thickness and in-plane flaw dimensions were varied to identify the inspection capability limitations of advanced ultrasonics for thick composites. The results presented in this study demonstrate an inverse relationship between the ability to find delaminations and plate thicknesses, with inspections successful at depths up to 74 mm. When the delamination thickness exhibited surface-to-surface contact, the inspection capability was reduced to 35 mm. There was an exponential decay relationship between the accuracy of the flaw depth measurement and plate thickness, likely due to the necessity of low probe frequencies. The effective inspection depth was determined to be in the range of 1 to 20 times the wavelength. It is speculated that the accuracy of measurements could be improved using probes with novel coupling solutions, and detectors with optimised signal processing/filtration algorithms.

Cumulative Experience of Neighborhood Walkability and Change in Weight and Waist Circumference in REGARDS.

Neighborhood walkability-features of the built environment that promote pedestrian activity-has been associated with greater physical activity and lower body mass index (BMI; calculated as weight (kg)/height (m)2) among neighborhood residents. However, much of the literature has been cross-sectional and only a few cohort studies have assessed neighborhood features throughout follow-up. Using data from the Reasons for Geographic and Racial Differences in Stroke Study (2003-2016) and a neighborhood walkability index (NWI) measured annually during follow-up, we assessed whether the cumulative experience of neighborhood walkability (NWI-years) predicted BMI and waist circumference after approximately 10 years of follow-up, controlling for these anthropometric measures at enrollment. Analyses were adjusted for individual-level sociodemographic covariates and the cumulative experience of neighborhood poverty rate and neighborhood greenspace coverage. Almost a third (29%) of participants changed address at least once during follow-up. The first change of residence, on average, brought the participants to neighborhoods with higher home values and lower NWI scores than their originating neighborhoods. Compared with those having experienced the lowest quartile of cumulative NWI-years, those who experienced the highest quartile had 0.83 lower BMI (95% confidence interval, -1.5, -0.16) and 1.07-cm smaller waist circumference (95% confidence interval, -1.96, -0.19) at follow-up. These analyses provide additional longitudinal evidence that residential neighborhood features that support pedestrian activity are associated with lower adiposity.

Neighborhood Food Environment and Birth Weight Outcomes in New York City.

Importance: Infants born with unhealthy birth weight are at greater risk for long-term health complications, but little is known about how neighborhood characteristics (eg, walkability, food environment) may affect birth weight outcomes. Objective: To assess whether neighborhood-level characteristics (poverty rate, food environment, and walkability) are associated with risk of unhealthy birth weight outcomes and to evaluate whether gestational weight gain mediated these associations. Design, Setting, and Participants: The population-based cross-sectional study included births in the 2015 vital statistics records from the New York City Department of Health and Mental Hygiene. Only singleton births and observations with complete birth weight and covariate data were included. Analyses were performed from November 2021 to March 2022. Exposures: Residential neighborhood-level characteristics, including poverty, food environment (healthy and unhealthy food retail establishments), and walkability (measured by both walkable destinations and a neighborhood walkability index combining walkability measures like street intersection and transit stop density). Neighborhood-level variables categorized into quartiles. Main Outcomes and Measures: The main outcomes were birth certificate birth weight measures including small for gestational age (SGA), large for gestational age (LGA), and sex-specific birth weight for gestational age z-score. Generalized linear mixed-effects models and hierarchical linear models estimated risk ratios for associations between density of neighborhood-level characteristics within a 1-km buffer of residential census block centroid and birth weight outcomes. Results: The study included 106 194 births in New York City. The mean (SD) age of pregnant individuals in the sample was 29.9 (6.1) years. Prevalence of SGA and LGA were 12.9% and 8.4%, respectively. Residence in the highest density quartile of healthy food retail establishments compared with the lowest quartile was associated with lower adjusted risk of SGA (with adjustment for individual covariates including gestational weight gain z-score: risk ratio [RR], 0.89; 95% CI 0.83-0.97). Higher neighborhood density of unhealthy food retail establishments was associated with higher adjusted risk of delivering an infant classified as SGA (fourth vs first quartile: RR, 1.12; 95% CI, 1.01-1.24). The RR for the association between density of unhealthy food retail establishments and risk of LGA was higher after adjustment for all covariates in each quartile compared with quartile 1 (second: RR, 1.12 [95% CI, 1.04-1.20]; third: RR, 1.18 [95% CI, 1.08-1.29]; fourth: RR, 1.16; [95% CI, 1.04-1.29]). There were no associations between neighborhood walkability and birth weight outcomes (SGA for fourth vs first quartile: RR, 1.01 [95% CI, 0.94-1.08]; LGA for fourth vs first quartile: RR, 1.06 [95% CI, 0.98-1.14]). Conclusions and Relevance: In this population-based cross-sectional study, healthfulness of neighborhood food environments was associated with risk of SGA and LGA. The findings support use of urban design and planning guidelines to improve food environments to support healthy pregnancies and birth weight.

Understanding the properties of intermittent catheters to inform future development.

Despite the extensive use of intermittent catheters (ICs) in healthcare, various issues persist for long-term IC users, such as pain, discomfort, infection, and tissue damage, including strictures, scarring and micro-abrasions. A lubricous IC surface is considered necessary to reduce patient pain and trauma, and therefore is a primary focus of IC development to improve patient comfort. While an important consideration, other factors should be routinely investigated to inform future IC development. An array of in vitro tests should be employed to assess IC's lubricity, biocompatibility and the risk of urinary tract infection development associated with their use. Herein, we highlight the importance of current in vitro characterisation techniques, the demand for optimisation and an unmet need to develop a universal 'toolkit' to assess IC properties.