POSTOPERATIVE CASTING OF BELOW-KNEE AMPUTATION REDUCES STUMP COMPLICATIONS.

INTRODUCTION: Against the technological advances in limb salvage, below-the-knee amputation (BKA) remains a common procedure. Although most elective BKA is classified as clean operation, the reported stump complication rate is much higher than predicted. Postoperative casting (PC) may reduce the number of these complications. The aim of this study was to compare the efficacy of elastic bandage with knee immobilizer (EBKI) and PC in BKA stump complications. METHODS: Retrospective cohort comparison design identified patients who underwent BKA between 2000-2023 for uncorrectable lower extremity ischemia, or excessive tissue loss secondary to non-correctable critical limb ischemia (CLI), excessive tissue loss secondary to CLI, infection, severe neuropathy, or the combination of these and stratified them into 2 cohorts based on their postoperative stump dressing: EBKI and PC. BKAs that were done for trauma or neoplastic process were excluded. The primary outcome measures: wound healing in 6 weeks and length of stay (LOS). SECONDARY OUTCOME MEASURES: stump injury, infection, dehiscence, necrosis, number of higher-level amputations, knee contracture and post BKA mobility with SIGAM score. RESULTS: 116 patients with 122 limbs (52 EBKI, 70 PC) were found who met inclusion criteria and analyzed. The groups were comparable in demographics and comorbidities and pre-operative variables, including mobility. The primary wound healing at 6 weeks was higher (p=0.007), wound dehiscence (p=0.01) and length of stay (p=0.006) was lower in the PC group compared to EBKI group. The PC group achieved higher SIGAM mobility score and lower number of contractures developed compared to the EBKI group. CONCLUSIONS: Applying and maintaining PC to the BKA stump during the first month of healing reduced the incidence of stump complications, shortened the LOS and improved post rehabilitation mobility results. We found no effect of PC on postoperative infections, stump necrosis and higher-level amputations.

Disentangling genetic, plastic and social learning drivers of sex-specific foraging behaviour in Trinidadian guppies (Poecilia reticulata).

Evolutionary biologists have long been interested in parsing out the roles of genetics, plasticity and their interaction on adaptive trait divergence. Since males and females often have different ecological and reproductive roles, separating how their traits are shaped by interactions between their genes and environment is necessary and important. Here, we disentangle the sex-specific effects of genetic divergence, developmental plasticity, social learning and contextual plasticity on foraging behaviour in Trinidadian guppies (Poecilia reticulata) adapted to high- or low-predation habitats. We reared second-generation siblings from both predation regimes with or without predator chemical cues, and with adult conspecifics from either high- or low-predation habitats. We then quantified their foraging behaviour in water with and without predator chemical cues. We found that high-predation guppies forage more efficiently than low-predation guppies, but this behavioural difference is context-dependent and shaped by different mechanisms in males and females. Higher foraging efficiency in high-predation females is largely genetically determined, and to a smaller extent socially learned from conspecifics. However, in high-predation males, higher foraging efficiency is plastically induced by predator cues during development. Our study demonstrates sex-specific differences in genetic versus plastic responses in foraging behaviour, a trait of significance in organismal fitness and ecosystem dynamics.

A closed surgical intensive care unit organization improves cardiac surgical patient outcomes.

Background: Intensive care unit (ICU) organization is a critical factor in optimizing patient outcomes. ICU organization can be divided into "OPEN" (O) and "CLOSED" (C) models, where the specialist or intensivist, respectively, assumes the role of primary physician. Recent studies support improved outcomes in closed ICUs, however, most of the available data is centered on ICUs generally or on subspecialty surgical patients in the setting of a subspecialized surgical intensive care unit (SICU). We examined the impact of closing a general SICU on patient outcomes following cardiac and ascending aortic surgery. Methods: A retrospective cohort of patients following cardiac or ascending aortic surgery by median sternotomy was examined at a single academic medical center one year prior and one year after implementation of a closed SICU model. Patients were divided into "OPEN" (O; n=53) and "CLOSED" (C; n=73) cohorts. Results: Cohorts were comparable in terms of age, race, and number of comorbid conditions. A significant difference in male gender (O: 60.4% vs. C: 76.7%, P=0.049), multiple procedure performed (O: 13.21% vs. C: 35.62%, P=0.019), and hospital readmission rates was detected (O: 39.6% vs. C: 9.6%, P=0.0003). Using a linear regression model, a closed model SICU organization decreased SICU length of stay (LOS). Using a multivariate logistic regression, being treated in a closed ICU decreased a patient's likelihood of having an ICU LOS greater than 48 hours. Conclusions: Our study identified a decreased ICU LOS and hospital readmission in cardiac and ascending aortic patients in a closed general SICU despite increased procedure complexity. Further study is needed to clarify the effects on surgical complications and hospital charges.

Methamphetamine spasm in the large caliber arteries-the severity is likely underestimated.

This report describes two cases of rarely reported, severe large arterial vascular spasms seen on computed tomography images after methamphetamine abuse. Although the effects of methamphetamine on the central nervous system and smaller arteries are relatively well known, its effects on large caliber arteries are rarely discussed. We present two cases of severe large arterial multisegmented vasospasm, captured on contrast-enhanced computed tomography, several hours after methamphetamine abuse. One of the patients was discharged without apparent tissue loss or organ failure. The other developed severe heart failure, liver failure, and toe gangrene. The publication of the de-identified images has been approved by the VA Central California Health Care System's Research and Development Committee and Privacy Officer. Vascular surgeons and, perhaps, acute care physicians, who are usually aware of small arterial vasospastic conditions, should also be aware of this methamphetamine-induced large arterial finding, which can be quite dramatic in appearance on imaging.

Evolutionary divergence of developmental plasticity and learning of mating tactics in Trinidadian guppies.

Behavioural plasticity is a major driver in the early stages of adaptation, but its effects in mediating evolution remain elusive because behavioural plasticity itself can evolve. In this study, we investigated how male Trinidadian guppies (Poecilia reticulata) adapted to different predation regimes diverged in behavioural plasticity of their mating tactic. We reared F2 juveniles of high- or low-predation population origins with different combinations of social and predator cues and assayed their mating behaviour upon sexual maturity. High-predation males learned their mating tactic from conspecific adults as juveniles, while low-predation males did not. High-predation males increased courtship when exposed to chemical predator cues during development; low-predation males decreased courtship in response to immediate chemical predator cues, but only when they were not exposed to such cues during development. Behavioural changes induced by predator cues were associated with developmental plasticity in brain morphology, but changes acquired through social learning were not. We thus show that guppy populations diverged in their response to social and ecological cues during development, and correlational evidence suggests that different cues can shape the same behaviour via different neural mechanisms. Our study demonstrates that behavioural plasticity, both environmentally induced and socially learnt, evolves rapidly and shapes adaptation when organisms colonize ecologically divergent habitats.

La plasticidad conductual es un factor importante en las primeras fases de adaptación, pero se conocen poco sus efectos sobre la evolución porque la plasticidad conductual en sí puede evolucionar. En este estudio, investigamos cómo los machos del guppy de Trinidad (Poecilia reticulata) adaptados a regímenes de depredación diferentes, han divergido en la plasticidad de su táctica de apareamiento. Criamos juveniles provenientes de poblaciones de alta y baja depredación hasta segunda generación (F2) bajo diferentes combinaciones de señales sociales y de depredación, y evaluamos su comportamiento de apareamiento al llegar a la madurez sexual. Los machos de alta depredación aprendieron su táctica de apareamiento de sus conespecíficos adultos, mientras que los machos de baja depredación no. Los machos de alta depredación aumentaron su cortejo al ser expuestos a señales de depredadores durante su desarrollo; mientras que los machos de baja depredación redujeron su cortejo en respuesta a señales inmediatas de depredadores, pero tan solo cuando no fueron expuestos a tales señales durante el desarrollo. Los cambios conductuales observados inducidos por las señales de depredación están asociados con una plasticidad en el desarrollo de la morfología cerebral, pero los cambios adquiridos por aprendizaje social no. En conclusión, demostramos que las poblaciones de guppy han divergido en su respuesta a señales sociales y ecológicas durante su desarrollo, y mostramos evidencia correlativa que sugiere que diferentes tipos de señales pueden influenciar el mismo comportamiento via mecanismos neuronales diferentes. Nuestro estudio muestra que la plasticidad conductual, tanto inducida por el medio ambiente combo aprendida socialmente, evoluciona rápidamente e influencia la adaptación durante la colonización de hábitats ecológicamente divergentes.

Maximizing Reflexive HCV RNA Testing of HCV Antibody-Reactive Samples Within United States Public Health Laboratories.

Hepatitis C virus (HCV) infection can cause significant morbidity and mortality if left untreated and diagnosis is the first step in any treatment regimen. In the United States, a two-step algorithm is recommended for detection of current HCV infection. The algorithm consists of an HCV antibody screening test followed by a supplemental test for HCV RNA if the HCV antibody test is reactive. To assess HCV testing practices and identify associated challenges, the Association of Public Health Laboratories (APHL) conducted a survey on HCV diagnostics practices of US public health laboratories. Additionally, APHL and the Centers for Disease Control and Prevention's (CDC) Division of Viral Hepatitis (DVH) convened a two-day meeting of HCV subject matter experts (SMEs) to identify opportunities for improvement in diagnosis of current HCV infection. Automatic reflexive HCV RNA testing of HCV antibody-reactive specimens was identified as a high priority target area by HCV SMEs and as a gap in laboratory practice by the APHL survey, which found that only 54% of respondent laboratories always automatically reflexed or referred an Ab-reactive specimen to an HCV RNA test. To facilitate accurate diagnosis and ensure that patients are not lost to follow up, laboratories and public health programs should work to ensure that the entire HCV testing algorithm (i.e., antibody and nucleic acid testing) can be completed with a sample(s) collected during a single patient visit.

Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer's Disease in AppNL-G-F Mice.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a leading cause of death in the United States. Neuroinflammation has been implicated in the progression of AD, and several recent studies suggest that peripheral immune dysfunction may influence the disease. Continuing evidence indicates that intestinal dysbiosis is an attribute of AD, and inflammatory bowel disease (IBD) has been shown to aggravate cognitive impairment. Previously, we separately demonstrated that an IBD-like condition exacerbates AD-related changes in the brains of the AppNL-G-F mouse model of AD, while probiotic intervention has an attenuating effect. In this study, we investigated the combination of a dietary probiotic and an IBD-like condition for effects on the brains of mice. Male C57BL/6 wild type (WT) and AppNL-G-F mice were randomly divided into four groups: vehicle control, oral probiotic, dextran sulfate sodium (DSS), and DSS given with probiotics. As anticipated, probiotic treatment attenuated the DSS-induced colitis disease activity index in WT and AppNL-G-F mice. Although probiotic feeding significantly attenuated the DSS-mediated increase in WT colonic lipocalin levels, it was less protective in the AppNL-G-F DSS-treated group. In parallel with the intestinal changes, combined probiotic and DSS treatment increased microglial, neutrophil elastase, and 5hmC immunoreactivity while decreasing c-Fos staining compared to DSS treatment alone in the brains of WT mice. Although less abundant, probiotic combined with DSS treatment demonstrated a few similar changes in AppNL-G-F brains with increased microglial and decreased c-Fos immunoreactivity in addition to a slight increase in Aß plaque staining. Both probiotic and DSS treatment also altered the levels of several cytokines in WT and AppNL-G-F brains, with a unique increase in the levels of TNFα and IL-2 being observed in only AppNL-G-F mice following combined DSS and probiotic treatment. Our data indicate that, while dietary probiotic intervention provides protection against the colitis-like condition, it also influences numerous glial, cytokine, and neuronal changes in the brain that may regulate brain function and the progression of AD.

Trends in the Prevalence of Hepatitis C Infection During Pregnancy and Maternal-Infant Outcomes in the US, 1998 to 2018.

Importance: Injection drug use is the primary risk factor for hepatitis C virus (HCV) infection in adults. More than one-third of newly reported HCV cases occur in women, particularly among persons aged 20 to 39 years. However, nationally representative data on HCV during pregnancy are limited. Objective: To estimate the temporal trend of HCV-positive pregnancies during the opioid epidemic and identify HCV-associated maternal and perinatal outcomes. Design, Setting, and Participants: A cross-sectional study was performed with data from the US, from calendar year 1998 through 2018. Data analysis was conducted from November 14, 2021, to May 14, 2023. Participants included women during in-hospital childbirth or spontaneous abortion in the National Inpatient Sample of the Healthcare Cost and Utilization Project. Exposure: Maternal HCV infection. Main Outcomes and Measures: The main outcome was the temporal trend, measured as change in the annual prevalence, in the prevalence of HCV positivity among pregnant women since the start of the opioid epidemic in the late 1990s. Secondary outcomes were the associations shown as relative odds between maternal HCV infection and maternal and perinatal adverse events. Results: During the study period, more than 70 million hospital admissions resulted in childbirth or spontaneous abortion. Among them, 137 259 (0.20%; 95% CI, 0.19%-0.21%) involved mothers with HCV; these individuals were more often White (77.4%; 95% CI, 76.1%-78.6%), low-income (40.0%; 95% CI, 38.6%-41.5%), and likely to have histories of tobacco (41.7%; 95% CI, 40.6%-42.9%), alcohol (1.8%; 95% CI, 1.6%-2.0%), and opioid (28.9%; 95% CI, 27.3%-30.6%) use compared with HCV-negative mothers. The median age of women with HCV was 28.0 (IQR, 24.3-32.2) years, and the median age of HCV-negative women was 27.2 (IQR, 22.7-31.8) years. The prevalence of HCV-positive pregnancies increased 16-fold during the study period, reaching 5.3 (95% CI, 4.9-5.7) cases per 1000 pregnancies in 2018. Age-specific prevalence increases ranged from 3-fold (age, 41-50 years) to 31-fold (age, 21-30 years). Higher odds of cesarean delivery, preterm labor, poor fetal growth, or fetal distress were associated with HCV-positivity during pregnancy. However, no significant differences were observed in gestational diabetes, preeclampsia, eclampsia, or stillbirths. Conclusions and Relevance: In this cross-sectional study, the prevalence of HCV-positive pregnancies increased markedly, and maternal HCV infection was associated with increased risks for adverse perinatal outcomes. These data may support recent recommendations for universal HCV screening with each pregnancy.

Adherence to Extended Venous Thromboembolism Prophylaxis and Outcomes After Complex Gastrointestinal Oncologic Surgery.

BACKGROUND: Clinical guidelines recommend extended venous thromboembolism (VTE) prophylaxis for cancer patients after major gastrointestinal (GI) operations. However, adherence to the guidelines has been low, and the clinical outcomes not well defined. METHODS: This study retrospectively analyzed a random 10 % sample of the 2009-2022 IQVIA LifeLink PharMetrics Plus database, an administrative claims database representative of the commercially insured population of the United States. The study selected cancer patients undergoing major pancreas, liver, gastric, or esophageal surgery. The primary outcomes were 90-day post-discharge VTE and bleeding. RESULTS: The study identified 2296 unique eligible operations. During the index hospitalization, 52 patients (2.2 %) experienced VTE, 74 patients (3.2 %) had postoperative bleeding, and 140 patients (6.1 %) had a hospital stay of at least 28 days. The remaining 2069 operations comprised 833 pancreatectomies, 664 hepatectomies, 295 gastrectomies, and 277 esophagectomies. The median age of the patients was 49 years, and 44 % were female. Extended VTE prophylaxis prescriptions were filled for 176 patients (10.4 % for pancreas, 8.1 % for liver, 5.8 % for gastric cancer, and 6.5 % for esophageal cancer), and the most used agent was enoxaparin (96 % of the patients). After discharge, VTE occurred for 5.2 % and bleeding for 5.2 % of the patients. The findings showed no association of extended VTE prophylaxis with post-discharge VTE (odds ratio [OR], 1.54; 95 % confidence interval [CI], 0.81-2.96) or bleeding (OR, 0.72, 95 % CI, 0.32-1.61). CONCLUSIONS: The majority of the cancer patients undergoing complex GI surgery did not receive extended VTE prophylaxis according to the current guidelines, and their VTE rate was not higher than for the patients who received it.

Positionality, intersectionality, power dynamics in community participatory research to define public safety in Black communities.

Community-based participatory research (CBPR) is necessary for shifting knowledge and empowering community members to establish ownership over research. It was used in this current project to study safety in predominately Black communities. Findings illustrate how the embodiment of power was a present theme and impacted the partnerships among the academics and community, as well as defining "who" could speak on the issues the project was attempting to address. This paper builds upon previous research in CBPR findings to illustrate how community leaders can shape the research, the importance of defining community, and the need to bring to the forefront issues of intersectionality and positionality. In doing so, it attempts to reshape existing CBPR models to better account for the fluid, interactive relationships among the academics, community researchers, and the community leader and expand upon the role of intersectionality in these relationships.

A searchable image resource of Drosophila GAL4 driver expression patterns with single neuron resolution.

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of Drosophila neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here, we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 74,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between neurons identified by electron or light microscopy. Identifying individual neurons that make up each GAL4 expression pattern improves the prediction of split-GAL4 combinations targeting particular neurons. To this end, we have made the images searchable on the NeuronBridge website. We demonstrate the potential of NeuronBridge to rapidly and effectively identify neuron matches based on morphology across imaging modalities and datasets.

Hanging under the ledge: synergistic consequences of UVA and UVB radiation on scyphozoan polyp reproduction and health.

Overexposure to ultraviolet radiation (UVR) emitted by the sun can damage and kill living cells in animals, plants, and microorganisms. In aquatic environments, UVR can penetrate nearly 47 m into the water column, severely impacting many marine organisms. Jellyfish are often considered resilient to environmental stressors, potentially explaining their success in environmentally disturbed areas, but the extent of their resilience to UVR is not well known. Here, we tested resiliency to UVR by exposing benthic polyps of the moon jellyfish, Aurelia sp., to UVA and UVB-the two types of UVR that reach Earth's surface-both separately and in combination. We quantified asexual reproduction rates and polyp attachment to hard substrate, in addition to qualitative observations of polyp health. There were no differences in asexual reproduction rates between polyps exposed to isolated UVA and polyps that received no UVR. Polyps reproduced when exposed to short term (∼7-9 days) isolated UVB, but long-term exposure limited reproduction and polyp attachment to the substrate. When exposed to both UVA and UVB, polyps were unable to feed and unable to remain attached to the substrate, did not reproduce, and ultimately, experienced 100% mortality within 20 days. Although many studies only examine the effects of UVB, the combination of UVA and UVB here resulted in greater negative impacts than either form of UVR in isolation. Therefore, studies that only examine effects of UVB potentially underestimate environmentally relevant effects of UVR. These results suggest that polyps are unsuccessful under UVR stress, so the planula larval stage must settle in low-UVR environments to establish the success of the polyp stage.

Developmental toxicity of remdesivir, an anti-COVID-19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells.

BACKGROUND: Remdesivir is an antiviral drug approved for the treatment of COVID-19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three-dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively. METHODS: MEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes. RESULTS: The mouse MEB morphogenesis was impaired by remdesivir at 1-8 µM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS-441524 and GS-621763, presumptive anti-COVID-19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1-8 µM. CONCLUSIONS: Remdesivir impaired mouse and human MEBs at concentrations that are comparable to the therapeutic plasma levels in humans, urging further investigation into the potential impact of remdesivir on developing embryos.

Prospective, multi-site study of patient outcomes after implementation of the TREWS machine learning-based early warning system for sepsis.

Early recognition and treatment of sepsis are linked to improved patient outcomes. Machine learning-based early warning systems may reduce the time to recognition, but few systems have undergone clinical evaluation. In this prospective, multi-site cohort study, we examined the association between patient outcomes and provider interaction with a deployed sepsis alert system called the Targeted Real-time Early Warning System (TREWS). During the study, 590,736 patients were monitored by TREWS across five hospitals. We focused our analysis on 6,877 patients with sepsis who were identified by the alert before initiation of antibiotic therapy. Adjusting for patient presentation and severity, patients in this group whose alert was confirmed by a provider within 3 h of the alert had a reduced in-hospital mortality rate (3.3%, confidence interval (CI) 1.7, 5.1%, adjusted absolute reduction, and 18.7%, CI 9.4, 27.0%, adjusted relative reduction), organ failure and length of stay compared with patients whose alert was not confirmed by a provider within 3 h. Improvements in mortality rate (4.5%, CI 0.8, 8.3%, adjusted absolute reduction) and organ failure were larger among those patients who were additionally flagged as high risk. Our findings indicate that early warning systems have the potential to identify sepsis patients early and improve patient outcomes and that sepsis patients who would benefit the most from early treatment can be identified and prioritized at the time of the alert.

Factors driving provider adoption of the TREWS machine learning-based early warning system and its effects on sepsis treatment timing.

Machine learning-based clinical decision support tools for sepsis create opportunities to identify at-risk patients and initiate treatments at early time points, which is critical for improving sepsis outcomes. In view of the increasing use of such systems, better understanding of how they are adopted and used by healthcare providers is needed. Here, we analyzed provider interactions with a sepsis early detection tool (Targeted Real-time Early Warning System), which was deployed at five hospitals over a 2-year period. Among 9,805 retrospectively identified sepsis cases, the early detection tool achieved high sensitivity (82% of sepsis cases were identified) and a high rate of adoption: 89% of all alerts by the system were evaluated by a physician or advanced practice provider and 38% of evaluated alerts were confirmed by a provider. Adjusting for patient presentation and severity, patients with sepsis whose alert was confirmed by a provider within 3 h had a 1.85-h (95% CI 1.66-2.00) reduction in median time to first antibiotic order compared to patients with sepsis whose alert was either dismissed, confirmed more than 3 h after the alert or never addressed in the system. Finally, we found that emergency department providers and providers who had previous interactions with an alert were more likely to interact with alerts, as well as to confirm alerts on retrospectively identified patients with sepsis. Beyond efforts to improve the performance of early warning systems, efforts to improve adoption are essential to their clinical impact and should focus on understanding providers' knowledge of, experience with and attitudes toward such systems.

Isolation and Whole-Genome Sequencing of Four Antibiotic-Producing Pseudomonas Strains.

Here, we report the isolation, whole-genome sequencing, and annotation of four novel Pseudomonas isolates. We also evaluate the biosynthetic potential of each genome.

Pilot Study of Feeding Tube Education Using a Graphic-Based Course.

BACKGROUND: Residents receive little formal education about feeding tubes; however, patients experience fewer complications if a formal feeding tube curriculum is implemented. OBJECTIVE: The aim of this study was to evaluate a graphics-based course for internal medicine residents. METHODS: Internal medicine residents participated in a new course on feeding tube placement and management. Surveys administered before and after the course assessed resident comfort level with the material. RESULTS: Based on a 10-point Likert scale, mean improvement in comfort level for 4 scenarios was 1.69, 2.13, 2.44, and 3.07 points (P < 0.001 for all). Ninety-four percent of participants reported the graphics were helpful. CONCLUSION: The new course significantly improved resident comfort level regarding feeding tube placement and management. The use of graphics played a role in increasing residents' understanding.