Calcium Imaging in Drosophila.

Ex vivo calcium imaging in Drosophila opens an expansive amount of research avenues for the study of live signal propagation through complex tissue. Here, we describe how to isolate Drosophila organs of interest, like the developing wing imaginal disc and larval brain, culture them for extended periods, up to 10 h, and how to image the calcium dynamics occurring within them using genetically encoded biosensors like GCaMP. This protocol enables the study of complex calcium signaling dynamics, which is conserved throughout biology in such processes as cell differentiation and proliferation, immune reactions, wound healing, and cell-to-cell and organ-to-organ communication, among others. These methods also allow pharmacological compounds to be tested to observe effects on calcium dynamics with the applications of target identification and therapeutic development.

Analysis of the interplay between proximal lower limb and foot joint structures as a mechanical predictor of neuropathic ulceration.

BACKGROUND: Diabetes-related foot ulcers are a leading cause of morbidity and mortality globally, in which the most significant contributing factor is peripheral neuropathy. The purpose of this research was to evaluate the influence of diabetic peripheral neuropathy and ulceration on lower limb and foot joint kinematics during gait. RESEARCH QUESTION: Are there any significant alterations lower limb and foot joint kinematics during gait in the presence of active and history of diabetic neuropathic ulceration? METHODS: A prospective, cross-sectional study was conducted, recruiting eighty adult participants who were equally divided into four groups, namely, the diabetes (DM), diabetic peripheral neuropathy (DPN), active diabetic neuropathic ulceration (DNU) and history of diabetic neuropathic ulceration (DHNU) groups. Three-dimensional gait analysis was performed, and participants were instructed to walk barefoot over a 10-m walkway at self-selected speed. The acquired pelvic, hip, knee, ankle and foot joint segmental kinematic data was compared between individuals with and without active neuropathic ulceration. RESULTS: Mean scores between the four independent groups was performed using the Kruskal-Wallis test. Participants within the DNU and DHNU groups demonstrated significantly reduced knee flexion, ankle dorsiflexion and first metatarsal dorsiflexion kinematics with resultant increased anterior pelvic tilt, hip flexion and midtarsal kinematics (all values p<0.01) when compared to participants within the DM and DPN groups. SIGNIFICANCE: Through the integration of a more individualised, biomechanical approach, the findings in this study may provide improved preventative and management strategies of ulceration amongst the diabetic population.

Distribution and Characteristics of Blackwater Rivers and Streams of the Contiguous United States.

Blackwater rivers and streams have stained or tea-colored water from tannins released by decaying plant matter. Natural conditions in these waters often differ from non-blackwater systems. For example, the pH and oxygen levels in waters can be very low, but completely natural. We examined an existing USEPA data set and found that blackwaters existed across the contiguous United States but were most common in the east. Water chemistry showed differences between blackwater and non-blackwater sites, but differences were not consistent across ecoregions making national scale generalizations difficult. Physical habitat data analysis did not show dramatic differences between blackwater and non-blackwater sites. Blackwater typically arises from streams that drain tannin-rich bogs/muskeg and wetlands, so as expected blackwater sites had a shorter Euclidean distance to wetlands than non-blackwater sites and existed in watersheds with a higher percentage of wetland habitat. Blackwaters in Northern and Temperate Plains tended to have higher acid neutralizing capacity, conductivity, and lower True Color; a visual color scale used for water purity. We posit that differences were because Color and Dissolved Organic Carbon at these sites were from buried wetland deposits rather than contemporary wetland habitats. Research needs that may increase our understanding and management of blackwaters include development of an operational definition that includes a classification framework and reference conditions for different blackwater types, identification of stressors and their associated dynamics that negatively impact blackwater systems, and development of data-driven, consistent, and repeatable assessment methods, including development of targets, protective of unique conditions in blackwater rivers and streams.

The fallacy of a roadmap computed tomography after an abdominal gunshot wound: A road that leads to nowhere.

BACKGROUND: The 2019 Western Trauma Association guidelines recommend an abdominopelvic computed tomography (CTAP) in patients with a question of abdominal penetration after a gunshot wound. However, it is common practice to obtain a CTAP to provide a roadmap for an operation or to potentially alter management even in patients with classic indications for a laparotomy. The hypothesis for this study was that a CTAP for preoperative planning has no value in patients with an abdominal gunshot wound. METHODS: This was a retrospective study from 2017 to 2022 of patients with an abdominal gunshot wound who had a preoperative CTAP. Data collection included clinical characteristics and CTAP and operative findings. Admission hypotension, abdominal pain and/or peritonitis, evisceration, and a transabdominal trajectory were considered clear indications for laparotomy. Computed tomography and operative findings were compared to determine concordance and if computed tomography altered management. RESULTS: There were 149 patients included in the study, of which 72.5% had a clear indication for laparotomy. The CTAP findings were concordant with operative findings in 57.0% of patients, while additional injuries were found at laparotomy in 36.2% of patients. Based on CTAP, a negative diagnostic angiogram was performed in three patients (2.0%). Three patients (2.0%) underwent a trial of nonoperative management based on CTAP findings. All underwent laparotomy after a clinical change. Six patients (4.0%) had a nontherapeutic operation; all patients had findings suspicious for either a hollow viscous injury or a vascular injury on preoperative imaging. CONCLUSION: While a CTAP scan may help to define an intra-abdominal trajectory when the trajectory is unclear, it does not alter management in those with indications for operation. In addition, CTAP missed injuries in a third of patients and contributed to all six nontherapeutic laparotomies. A preoperative CTAP has minimal value in patients who have indications for an operation. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level IV.

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and the etiology of the disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental and as-yet unidentified genetic contributors and their interactions. Previous research linked genetic variation on chromosome 6 to increased CRC risk. This region harbors multiple immune genes, including the gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand for the Natural Killer Group 2D receptor (NKG2D), a receptor expressed on Natural Killer (NK) cells and other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable CRC outcomes, we hypothesized that germline genetic variation in MICA could influence CRC risk. In a discovery set of 40,125 cases and controls, we show that the minor G allele at Chr6:31373718C>G (hg19) is associated with increased risk for CRC (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.04 - 1.15, p = 0.0009). The effect is stronger in EOCRC (OR = 1.26, 95% CI 1.08 - 1.44, p = 0.0023) than in those 50 and over (OR = 1.07, 95% CI 1.02 - 1.13; p = 0.012) (Ratio of ORs = 1.32, 95% CI 1.14 - 1.52, p = 0.0002). In an independent validation set of 77,983 cases and controls, the adjusted interaction by age-of-onset was significant at OR = 1.15 (95% CI 1.03 - 1.34, p = 0.0150) with a higher risk in EOCRC. Expression quantitative trait locus analysis in normal colonic epithelia showed that MICA RNA expression decreases linearly with each additional copy of the minor G allele (p = 3.345 × 10e-18). Bulk RNA analysis of the tumor immune microenvironment revealed that tumors from patients with CG or GG genotypes have lower resting and activated NK cell infiltration as compared to tumors from patients with CC genotype. Multiplex immunofluorescence analysis demonstrated that patients with a G allele (i.e. CG or GG genotype, but not CC genotype) have a statistically significant decrease in the number of NK cells in tumor compared to adjacent normal colonic mucosa. Taken together, population-based epidemiologic, molecular, genetic, cellular and immunologic evidence demonstrate that MICA genotype is associated with increased risk of EOCRC and reduced number of NK cells in colorectal tumors, suggesting that patients with a G allele have altered NK cell-mediated immunosurveillance. These novel findings suggest that EOCRC may have a previously unrecognized innate immune-mediated etiology which merits further investigation.

The potential mediating role of the gut microbiome and metabolites in the association between PFAS and kidney function in young adults: A proof-of-concept study.

BACKGROUND: Chronic kidney disease (CKD) affects over 10 % of the global population and can lead to kidney failure and death. Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with increased risk of CKD, yet studies examining the mechanisms linking PFAS and kidney function are lacking. In this exploratory study, we examined longitudinal associations of PFAS exposure with kidney function, and tested if associations were mediated by altered gut bacterial taxa or plasma metabolites using a multi-omics mediation analysis. METHODS: Seventy-eight young adults from the Children's Health Study were included in this longitudinal cohort study. At baseline, seven plasma PFAS and untargeted plasma metabolomics were measured using liquid chromatography/mass-spectrometry. Baseline gut bacterial abundance was characterized using 16S rRNA sequencing and examined at the genus level. At follow-up, serum creatinine and cystatin-C concentrations were quantified to estimate glomerular filtration rate (eGFR). High-dimensional multi-omics analyses were conducted to assess the association between baseline PFAS exposure with follow-up eGFR, mediated by gut microbiome and circulating metabolite levels. RESULTS: PFAS burden score, a variable developed to estimate exposure to chemical mixtures, was associated with kidney function. Each standard deviation increase in baseline PFAS burden score was associated with a 2.4 % lower eGFR at follow-up (95 % CI:[0.1 %,4.8 %]). Following high-dimensional mediation analyses with the microbiome and circulating metabolites, a joint component (characterized by reduced Lachnospiraceae and 17b-estradiol and increased succinate, retinoate and dodecanoic acid) and a metabolite component (characterized by increased hypotaurine and decreased D-pinitol and ureidopropionate) mediated 38 % and 50 % of the effect between PFAS burden score and eGFR, respectively. CONCLUSION: Our proof-of-concept analysis provides the first evidence that reduced short-chain fatty acid-producing bacteria and anti-inflammatory metabolites may link PFAS exposure with impaired kidney function. This study raises the possibility of future targeted interventions that can alter gut microbiome or circulating metabolite profiles to prevent PFAS induced kidney damage.

Survival Following Diagnosis of HIV-Associated Kaposi Sarcoma Among Adults in East Africa in the "Treat-All" Era.

Background: Despite widespread access to antiretroviral therapy (ART) in the "Treat All" era, HIV-associated Kaposi sarcoma (KS) remains among the most common malignancies in sub-Saharan Africa. Survival after KS diagnosis has historically been poor in Africa, but knowledge whether survival has changed at the population level in the contemporary era has been limited by lack of community-representative surveillance and monitoring systems. Methods: We identified all adult persons living with HIV (PLWH) with a new diagnosis of KS made between 2016 and 2019 during outpatient or inpatient care at prototypical primary care-providing medical facilities in Kenya and Uganda using rapid case ascertainment. Participants were subsequently followed for vital status, including community tracking for those who became lost to follow-up. Findings: Among 411 participants with newly diagnosed KS, 71% were men, median age was 34 (IQR: 30 to 41) years, and 91% had ACTG T1 tumor extent. Over a median follow-up of 7.8 (IQR: 2.4 to 17.9) months, cumulative incidence of death (95% CI) at months 6, 12 and 18 were 34% (30% to 39%), 41% (36% to 46%) and 45% (40% to 51%), respectively. Having the highest number of anatomic sites (11 to 16) harboring KS lesions (hazard ratio 2.2 (95% CI: 1.3-3.8) compared to 1 to 3 sites) and presence of oral KS lesions (hazard ratio 2.2 (95% CI: 1.4-3.3)) were independently associated with higher mortality. Lower hemoglobin and CD4 count as well as higher plasma HIV RNA were also associated with higher mortality. Interpretation: Among PLWH with newly diagnosed KS in East Africa in the "Treat All" era, survival was poor and related to mucocutaneous extent of KS. The findings emphasize the need for better control of KS in Africa, including novel approaches for earlier detection, better linkage to oncologic care, and more potent therapy.

Tribological Properties of Nitrate Graphite Foils.

This study investigates the tribological properties of graphite foils (GF) with densities of 1.0, 1.3, and 1.6 g/cm3, produced from purified natural graphite of different particle sizes (40-80 µm, 160-200 µm, >500 µm). Surface roughness was measured after cold rolling and friction testing at static (0.001 mm/s) and dynamic conditions (0.1 Hz and 1 Hz). Results showed that static friction tests yielded similar roughness values (Sa ≈ 0.5-0.7 µm, Sq ≈ 0.5-1.0 µm) across all densities and particle sizes. Dynamic friction tests revealed increased roughness (Sa from 0.7 to 3.5 µm, Sq from 1.0 to 6.0-7.0 µm). Friction coefficients (µ) decreased with higher sliding speeds, ranging from 0.22 to 0.13. GF with 40-80 µm particles had the lowest friction coefficient (µ = 0.13-0.15), while 160-200 µm particles had the highest (µ = 0.15-0.22). Density changes had minimal impact on friction for the 40-80 µm fraction but reduced friction for the 160-200 µm fraction. Young's modulus increased with density and decreased with particle size, showing values from 127-274 MPa for 40-80 µm, 104-212 MPa for 160-200 µm, and 82-184 MPa for >500 µm. The stress-strain state in the graphite foil samples was simulated under normal and tangential loads. This makes it possible to investigate the effect of the anisotropy of the material on the stress concentration inside the sample, as well as to estimate the elasticity modulus under normal compression. Structural analyses indicated greater plastic deformation in GF with 40-80 µm particles, reducing coherent-scattering region size from 28 nm to 24 nm. GF samples from 160-200 µm and >500 µm fractions showed similar changes, expanding with density increase from 18 nm to 22 nm. Misorientation angles of GF nanocrystallites decreased from 30° to 27° along the rolling direction (RD). The coherent scattering regions of GF with 40-80 µm particles increased, but no significant changes in the coherent scattering regions were observed for the 160-200 µm and >500 µm fractions during dynamic friction tests. Microstrains and residual macrostresses in GF increased with density for all fractions, expanding under higher friction-induced loads. Higher values of both stresses indicate a higher level of accumulated deformation, which appears to be an additional factor affecting the samples during friction testing. This is reflected in the correlation of the results with the roughness and friction coefficient data of the tested samples.

Engineering novel adeno-associated viruses (AAVs) for improved delivery in the nervous system.

Harnessing adeno-associated virus (AAV) vectors for therapeutic gene delivery has emerged as a progressively promising strategy to treat disorders of both the central nervous system (CNS) and peripheral nervous system (PNS), and there are many ongoing clinical trials. However, unique physiological and molecular characteristics of the CNS and PNS pose obstacles to efficient vector delivery, ranging from the blood-brain barrier to the diverse nature of nervous system disorders. Engineering novel AAV capsids may help overcome these ongoing challenges and maximize therapeutic transgene delivery. This article discusses strategies for innovative AAV capsid development, highlighting recent advances. Notably, advances in next generation sequencing and machine learning have sparked new approaches for capsid investigation and engineering. Furthermore, we outline future directions and additional challenges in AAV-mediated gene therapy in the CNS and PNS.

Social reward and nonsocial reward processing across the adult lifespan: An interim multi-echo fMRI and diffusion dataset.

Social relationships change across the lifespan as social networks narrow and motivational priorities shift. These changes may affect, or reflect, differences in how older adults make decisions related to processing social and non-social rewards. While we have shown initial evidence that older adults have a blunted response to some features of social reward, further work in larger samples is needed to replicate our results and probe the extent to which age-related differences translate to real world consequences, such as financial exploitation. To address this gap, we are conducting a 5-year study funded by the National Institute on Aging (NIH R01-AG067011). Over the course of the funding period (2021-2026), this study seeks to: 1) characterize neural responses to social rewards across adulthood; 2) relate those responses to risk for financial exploitation and sociodemographic factors tied to risk; and 3) examine changes in risk for financial exploitation over time in healthy and vulnerable groups of older adults. This paper describes the preliminary release of data for the larger study. Adults (N = 114; 40 male / 70 female / 4 other or non-binary; 21-80 years of age M = 42.78, SD = 17.13) were recruited from the community to undergo multi-echo fMRI while completing tasks that measure brain function during social reward and decision making. Tasks probe neural response to social reward (e.g., peer vs. monetary feedback) and social context and closeness (e.g., sharing a monetary reward with a friend compared to a stranger). Neural response to social decision making is probed via economic trust and ultimatum games. Functional data are complimented by a T1 weighted anatomical scan and multi-shell diffusion-weighted imaging (DWI) to enable tractography and assess neurite orientation dispersion and density. Overall, this dataset has extensive potential for re-use, including leveraging multimodal neuroimaging data, within subject measures of fMRI data from different tasks - data features that are rarely seen in an adult lifespan dataset. Finally, the functional data will allow for developmentally sensitive cross-sectional analyses of differences in brain response to nuanced differences in reward contexts and outcomes (e.g., monetary vs. social; sharing winnings with a friend vs. stranger; stranger vs. computer).

A behavioral dataset of predictive decisions given trends in information across adulthood.

Making early and good predictions is a critical feature of decision making in domains such as investing and predicting the spread of diseases. Past literature indicates that people use recent and longer-term trends to extrapolate future outcomes. Nonetheless, less is known about what differentiates the strategies people use to make better predictions than others. Furthermore, factors underlying predictive judgments could be an important behavioral component in psychosocial research investigating manic-depression, anxiety, and age effects. Additionally, predictive judgments may be moderated based on the experience of living in areas with greater income inequality. To address these issues, we used investment tasks where participants had to predict future outcomes of their investments based on a trend in information. In the task, participants predicted how many tokens a gold mine would produce on the twelfth turn. On each turn, participants could ask for more information at a cost, or make a prediction about whether the gold mine would produce more or less than 100 tokens by the 12th turn. The trend was determined by function type (exponential and inverse exponential functions), whether the function was more linear or curved (growth factors), and good or bad outcomes (final values). This paradigm could help disentangle to what degree people use recent or longer-term information to inform their predictive judgments. We used Qualtrics to conduct this study. We also collected questionnaire data quantifying anxiety, impulsivity, risk attitudes, manic-depressive symptoms, and other psychosocial characteristics. The study was administered to adults with age ranges across the lifespan (N = 360; 225 male, 132 female; 3 nonbinary; mean age: 44.3 years; SD: 15.4 years, min: 18 years, max: 78 years). Additionally, we sampled across areas with high- and low-income inequality, thereby allowing researchers to investigate if value-based decisions are associated with participants' local communities. We outline potential ways to use and reuse this data, including exploring how individual differences are associated with predictive judgments.

An extension of latent unknown clustering integrating multi-omics data (LUCID) incorporating incomplete omics data.

Motivation: Latent unknown clustering integrating multi-omics data is a novel statistical model designed for multi-omics data analysis. It integrates omics data with exposures and an outcome through a latent cluster, elucidating how exposures influence processes reflected in multi-omics measurements, ultimately affecting an outcome. A significant challenge in multi-omics analysis is the issue of list-wise missingness. To address this, we extend the model to incorporate list-wise missingness within an integrated imputation framework, which can also handle sporadic missingness when necessary. Results: Simulation studies demonstrate that our integrated imputation approach produces consistent and less biased estimates, closely reflecting true underlying values. We applied this model to data from the ISGlobal/ATHLETE "Exposome Data Challenge Event" to explore the association between maternal exposure to hexachlorobenzene and childhood body mass index by integrating incomplete proteomics data from 1301 children. The model successfully estimated proteomics profiles for two clusters representing higher and lower body mass index, characterizing the potential profiles linking prenatal hexachlorobenzene levels and childhood body mass index. Availability and implementation: The proposed methods have been implemented in the R package LUCIDus. The source code is available at https://github.com/USCbiostats/LUCIDus.

12.1 terabit/second data center interconnects using O-band coherent transmission with QD-MLL frequency combs.

Most current Data Center Interconnects (DCI) use intensity modulation direct detection (IMDD) configurations due to their low complexity and cost. However, significant scaling challenges allow coherent solutions to become contenders in these short reach applications. We present an O-band coherent optical fiber transmission system based on Quantum Dot-Mode Locked Lasers (QD-MLLs) using two independent free-running comb lasers, one each for the carrier and the Local Oscillator (LO). Using a comb-to-comb configuration, we demonstrate a 10 km single mode fiber, O-band, coherent, heterodyne, 12.1 Tbps system operating at 0.47 Tbps/λ using 26 λs. We used fewer comb lines (26 λs), faster symbol rate (56 GBaud) and higher constellation cardinality (32 QAM) relative to the highest capacity C-band systems reported to date. Through design, analysis, and experimentation, we quantify the optimum comb line spacing for this use case. We compare potential configurations for increasing data center interconnect capacities whilst reducing power consumption, complexity, and cost.

Characterization of additive gene-environment interactions for colorectal cancer risk.

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

Impact of the Coronavirus Disease 2019 Pandemic on Substance Use Disorder Risk Among People Living With Human Immunodeficiency Virus (HIV) Enrolled in HIV Care in the United States: An Interrupted Time Series Analysis.

Background: Rising overdose deaths globally and increased social isolation during the coronavirus disease 2019 (COVID-19) pandemic may have disproportionately impacted people with human immunodeficiency virus (PWH) with substance use disorders (SUD). We examined trends in SUD risk among PWH before and after the COVID-19 shelter-in-place (SIP) mandate. Methods: Data were collected between 2018 and 2022 among PWH enrolled across 8 US sites in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We evaluated changes in moderate/high SUD risk after SIP using interrupted time series analyses. Results: There were 7126 participants, including 21 741 SUD assessments. The median age was 51 (interquartile range, 39-58) years; 12% identified as Hispanic or Latino/Latina, 46% Black/African American, and 46% White. Moderate/high SUD risk increased continuously after the pandemic's onset, with 43% (95% confidence interval [CI], 40%-46%) endorsing moderate/high SUD risk post-SIP, compared to 24% (95% CI, 22%-26%) pre-SIP (P < .001). There were increases in the use of heroin, methamphetamine, and fentanyl, and decreases in prescription opioids and sedatives post-SIP. Further, there was a decrease in reported substance use treatment post-SIP compared to pre-SIP (P = .025). Conclusions: The rising prevalence of SUD through late 2022 could be related to an increase in isolation and reduced access to substance use and HIV treatment caused by disruptions due to COVID-19. A renewed investment in integrated substance use treatment is vital to address the combined epidemics of substance use and HIV following the COVID-19 pandemic and to support resilience in the face of future disruptions.

Stop the Bleed-Wait for the Ambulance or Get in the Car and Drive? A Post Hoc Analysis of an EAST Multicenter Trial.

Background: The Stop the Bleed campaign gives bystanders an active role in prehospital hemorrhage control. Whether extending bystanders' role to private vehicle transport (PVT) for urban penetrating trauma improves survival is unknown, but past research has found benefit to police and PVT. We hypothesized that for penetrating trauma in an urban environment, where prehospital procedures have been proven harmful, PVT improves outcomes compared to any EMS or advanced life support (ALS) transport.Methods: Post-hoc analysis of an EAST multicenter trial was performed on adult patients with penetrating torso/proximal extremity trauma at 25 urban trauma centers from 5/2019-5/2020. Patients were allocated to PVT and any EMS or ALS transport using nearest neighbor propensity score matching. Univariate analyses included Wilcoxon signed rank or McNemar's Test and logistic regression.Results: Of 1999 penetrating trauma patients in urban settings, 397 (19.9%) had PVT, 1433 (71.7%) ALS transport, and 169 (8.5%) basic life support (BLS) transport. Propensity matching yielded 778 patients, distributed equally into balanced groups. PVT patients were primarily male (90.5%), Black (71.2%), and sustained gunshot wounds (68.9%). ALS transport had significantly higher ED mortality (3.9% vs 1.9%, P = 0.03). There was no difference in in-hospital mortality rate, hospital LOS, or complications for all EMS or ALS only transport patients.Conclusion: Compared to PVT, ALS, which provides more prehospital procedures than BLS, provided no survival benefit for penetrating trauma patients in urban settings. Bystander education incorporating PVT for early arrival of penetrating trauma patients in urban settings to definitive care merits further investigation.

Identification of proteins associated with type 2 diabetes risk in diverse racial and ethnic populations.

AIMS/HYPOTHESIS: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European. METHODS: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were applied to genome-wide association study summary statistics of 250,127 type 2 diabetes cases and 1,222,941 controls from different racial and ethnic populations. RESULTS: We identified three, 44 and one protein associated with type 2 diabetes risk in Asian, European and Hispanic/Latino populations, respectively. Meta-analysis identified 40 proteins associated with type 2 diabetes risk across the populations, including well-established as well as novel proteins not yet implicated in type 2 diabetes development. CONCLUSIONS/INTERPRETATION: Our study improves our understanding of the aetiology of type 2 diabetes in diverse populations. DATA AVAILABILITY: The summary statistics of multi-ethnic type 2 diabetes GWAS of MVP, DIAMANTE, Biobank Japan and other studies are available from The database of Genotypes and Phenotypes (dbGaP) under accession number phs001672.v3.p1. MESA genetic, proteome and covariate data can be accessed through dbGaP under phs000209.v13.p3. All code is available on GitHub ( https://github.com/Arthur1021/MESA-1K-PWAS ).

Identifying dose constraints for the parotid ducts to minimize patient-reported xerostomia: Is conventional mean dose sparing of the parotid glands sufficient?

BACKGROUND AND PURPOSE: The aim of this study was to identify dose constraints for the parotid ducts that limit patient-reported xerostomia and estimate whether these constraints are achieved during conventional parotid gland sparing radiation therapy (PGS-RT). METHODS AND MATERIALS: Thirty-eight oropharyngeal squamous cell carcinoma patients were treated prospectively on trial with MRI sialography-guided parotid duct sparing radiation therapy (PDS-RT). PDS-RT explicitly minimizes dose to the parotid ducts in addition to PGS-RT. Parotid duct dose constraints were identified that distinguished patients reporting high and low rates of xerostomia. Atlas-based parotid duct contours were generated on a retrospective cohort of similar patients where the parotid ducts were not contoured nor explicitly spared to estimate the dose received by the parotid ducts during PGS-RT. RESULTS: Patients whose intraglandular parotid ducts or total parotid ducts were planned for a mean dose < 14 Gy and < 12 Gy, respectively, reported significantly (p < 0.01) lower rates of xerostomia at 6 and 12 months post-RT. Patients receiving PDS-RT had average total and intraglandular duct doses of 11.6  and 13.6 Gy, respectively, compared to an estimated 23.8  and 22.1 Gy, for those receiving PGS-RT (p < 0.01). Only 6% (6/108) and 20% (22/108) of patients receiving PGS-RT were estimated to meet the dose constraints for the total ducts and intraglandular ducts, respectively. CONCLUSION: Parotid duct dose thresholds exist that appear to distinguish patients with and without xerostomia. The identified dose thresholds are frequently not met in PGS-RT plans. In addition to reducing the dose to the parotid gland(s), parotid duct sparing may also further reduce xerostomia.

Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence.

The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.