Laparoscopic totally extraperitoneal hernia repair in patients with a history of previous abdominopelvic surgery.

A retrospective cohort study of patients undergoing laparoscopic inguinal hernia repair compared short- and long-term outcomes between individuals with or without history of previous abdominopelvic surgery, aiming to determine the feasibility of totally extraperitoneal (TEP) repair within this population. All patients who underwent elective TEP inguinal hernia repair by one consultant surgeon across three London hospitals from January 2017 to May 2023 were retrospectively analysed to assess perioperative outcomes. Two hundred sixty-two patients were identified, of whom two hundred forty-three (93%) underwent laparoscopic TEP repair. The most frequent complications were haematoma (6.2%) and seroma (4.1%). Recurrence occurred in four cases (1.6% of operations, 1.1% of hernias). One hundred eighty-four patients (76%) underwent day-case surgery. There were no mesh infections or explanations, vascular or visceral injuries, port-site hernias, damage to testicle, or persisting numbness. There were no requirements for blood transfusion, returns to theatre, or readmissions within 30 days. There was one conversion to open and one death within 60 days of surgery. Eighty-three (34%) had a history of previous AP surgery. There was no significant difference in perioperative outcomes between the AP and non-AP arms. This finding carried true for subgroup analysis of 44 patients whose AP surgical history did not include previous inguinal hernia repair and for those undergoing repair of recurrent hernia. In expert hands, laparoscopic TEP repair is associated with excellent outcomes and low rates of long-term complications, and thus should be considered as standard for patients regardless of a history of AP surgery.

Tungsten-anisole complex provides 3,6-substituted cyclohexenes for highly diversified chemical libraries.

Medicinal chemists use vast combinatorial molecular libraries to develop leads for new pharmaceuticals. The syntheses of these compounds typically rely on coupling molecular fragments through atoms with planar (sp2) geometry. These so-called flat molecules often lack the protein binding site specificity needed to be an effective drug. Here, we demonstrate a coupling strategy in which a cyclohexene is used as a linker to connect two diverse molecular fragments while forming two new tetrahedral (sp3) stereocenters. These connections are made with the aid of a tungsten complex that activates anisole toward an unusual double protonation, followed by sequential nucleophilic additions. As a result, either cis- or trans-disubstituted cyclohexenes can be prepared with a range of chemical diversity unparalleled by other dearomatization methods.

Identification of SARS-CoV-2 variants in indoor dust.

Environmental surveillance of pathogens underlying infectious disease is critical to ensure public health. Recent efforts to track SARS-CoV-2 have utilized wastewater sampling to infer community trends in viral abundance and variant composition. Indoor dust has also been used for building-level inferences, though to date no sequencing data providing variant-scale resolution have been reported from dust samples, and strategies to monitor circulating variants in dust are needed to help inform public health decisions. In this study, we demonstrate that SARS-CoV-2 lineages can be detected and sequenced from indoor bulk dust samples. We collected 93 vacuum bags from April 2021 to March 2022 from buildings on The Ohio State University's (OSU) Columbus campus, and the dust was used to develop and apply an amplicon-based whole-genome sequencing protocol to identify the variants present and estimate their relative abundances. Three variants of concern were detected in the dust: Alpha, Delta, and Omicron. Alpha was found in our earliest sample in April 2021 with an estimated frequency of 100%. Delta was the primary variant present from October of 2021 to January 2022, with an average estimated frequency of 91% (±1.3%). Omicron became the primary variant in January 2022 and was the dominant strain in circulation through March with an estimated frequency of 87% (±3.2%). The detection of these variants on OSU's campus correlates with the circulation of these variants in the surrounding population (Delta p<0.0001 and Omicron p = 0.02). Overall, these results support the hypothesis that dust can be used to track COVID-19 variants in buildings.

An integrated analytical modeling framework for determining site-specific soil screening levels for PFAS.

Soils at many contaminated sites have accumulated a significant amount of per- and polyfluoroalkyl substances (PFAS) and may require remediation to mitigate leaching to groundwater. USEPA's current approaches for determining soil screening levels (SSLs) were developed for non-PFAS contaminants. Because many PFAS are interfacially-active with unique leaching behaviors in soils, the current non-PFAS-specific soil screening models may not be applicable. Following USEPA's general methodology, we develop a new modeling framework representing PFAS-specific transport processes for determining site-specific SSLs for PFAS-contaminated sites. We couple a process-based analytical model for PFAS leaching in the vadose zone and a dilution factor model for groundwater in an integrated framework. We apply the new modeling framework to two typical types of contaminated sites. Comparisons with the standard USEPA SSL approach suggest that accounting for the PFAS-specific transport processes may significantly increase the SSL for some PFAS. For the range of soil properties and groundwater recharge rates examined, while SSLs determined with the new model are less than a factor of 2 different from the standard-model values for less interfacially-active shorter-chain PFAS, they are up to two orders of magnitudes greater for more interfacially-active longer-chain PFAS. The new analytical modeling framework provides an effective tool for deriving more accurate site-specific SSLs and improving site characterization and remedial efforts at PFAS-contaminated sites.

Disproportionation chemistry in K2PtCl4 visualized at atomic resolution using scanning transmission electron microscopy.

The direct observation of a solid-state chemical reaction can reveal otherwise hidden mechanisms that control the reaction kinetics. However, probing the chemical bond breaking and formation at the molecular level remains challenging because of the insufficient spatial-temporal resolution and composition analysis of available characterization methods. Using atomic-resolution differential phase-contrast imaging in scanning transmission electron microscopy, we have visualized the decomposition chemistry of K2PtCl4 to identify its transient intermediate phases and their interfaces that characterize the chemical reduction process. The crystalline structure of K2PtCl4 is found to undergo a disproportionation reaction to form K2PtCl6, followed by gradual reduction to crystalline Pt metal and KCl. By directly imaging different Pt─Cl bond configurations and comparing them to models predicted via density functional theory calculations, a causal connection between the initial and final states of a chemical reaction is established, showcasing new opportunities to resolve reaction pathways through atomistic experimental visualization.

Tailoring Local Chemical Ordering via Elemental Tuning in High-Entropy Alloys.

Due to the large multi-elemental space desired for property screening and optimization, high-entropy alloys (HEAs) hold greater potential over conventional alloys for a range of applications, such as structural materials, energy conversion, and catalysis. However, the relationship between the HEA composition and its local structural/elemental configuration is not well understood, particularly in noble-metal-based HEA nanomaterials, hindering the design and development of nano-HEAs in energy conversion and catalysis applications. Herein, we determined precise atomic-level structural and elemental arrangements in model HEAs composed of RhPtPdFeCo and RuPtPdFeCo to unveil their local characteristics. Notably, by changing just one constituent element in the HEA (Rh to Ru), we found dramatic changes in the elemental arrangement from complete random mixing to a local single elemental ordering feature. Additionally, we demonstrate that the local ordering in RuPtPdFeCo can be further controlled by varying the Ru concentration, allowing us to toggle between local Ru clustering and distinct heterostructures in multicomponent systems. Overall, our study presents a practical approach for manipulating local atomic structures and elemental arrangements in noble-metal-based HEA systems, which could provide in-depth knowledge to mechanistically understand the functionality of noble-metal-based HEA nanomaterials in practical applications.

Early experience in use of videolaryngoscopy by a neonatal pre-hospital and retrieval service.

OBJECTIVE: To describe initial experience with use of the Glidescope Go videolaryngoscope by an Australian neonatal pre-hospital and retrieval service. METHODS: We conducted a 31-month retrospective review of an airway registry for neonates intubated by MedSTAR Kids clinicians. RESULTS: Twenty-two patients were intubated using the Glidescope Go, compared with 50 using direct laryngoscopy. First-pass success was 17/22 (77.3%) with the Glidescope Go and 38/50 (76%) with direct laryngoscopy. Complications occurred in 7/22 (32%) and 8/50 (16%), respectively. CONCLUSIONS: On initial review of this practice change, videolaryngoscopy allows neonatal tracheal intubation with a comparable success rate to direct laryngoscopy in a pre-hospital and retrieval setting.

MyoLoop: Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies.

Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-µm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.

Lithium carbonate-promoted mixed rare earth oxides as a generalized strategy for oxidative coupling of methane with exceptional yields.

The oxidative coupling of methane to higher hydrocarbons offers a promising autothermal approach for direct methane conversion, but its progress has been hindered by yield limitations, high temperature requirements, and performance penalties at practical methane partial pressures (~1 atm). In this study, we report a class of Li2CO3-coated mixed rare earth oxides as highly effective redox catalysts for oxidative coupling of methane under a chemical looping scheme. This catalyst achieves a single-pass C2+ yield up to 30.6%, demonstrating stable performance at 700 °C and methane partial pressures up to 1.4 atm. In-situ characterizations and quantum chemistry calculations provide insights into the distinct roles of the mixed oxide core and Li2CO3 shell, as well as the interplay between the Pr oxidation state and active peroxide formation upon Li2CO3 coating. Furthermore, we establish a generalized correlation between Pr4+ content in the mixed lanthanide oxide and hydrocarbons yield, offering a valuable optimization strategy for this class of oxidative coupling of methane redox catalysts.

Catalysts Prepared from Atomically Dispersed Ce(III) on MgO Rival Bulk Ceria for CO Oxidation.

Atomically dispersed cerium catalysts on an inert, crystalline MgO powder support were prepared by using both Ce(III) and Ce(IV) precursors. The materials were used as catalysts for CO oxidation in a once-through flow reactor and characterized by atomic-resolution scanning transmission electron microscopy, X-ray absorption near-edge structure spectroscopy, X-ray photoelectron spectroscopy, and temperature-programmed reduction, among other techniques, before and after catalysis. The most active catalysts, formed from the precursor incorporating Ce(III), displayed performance similar to that reported for bulk ceria under comparable conditions. The catalyst provided stable time-on-stream performance for as long as it was kept on-stream, 2 days, increasing slightly in activity as the atomically dispersed cerium ions were transformed into ceria nanodomains represented as CeOx and having increased reducibility on the MgO support. The results suggest how highly dispersed supported ceria catalysts with low cerium loadings can be prepared and may pave the way for improved efficiencies of cerium utilization in oxidation catalysis.

The Many Faces of Histidine Triad Nucleotide Binding Protein 1 (HINT1).

The histidine triad nucleotide binding protein 1 (HINT1) is a nucleoside phosphoramidase that has garnered interest due to its widespread expression and participation in a broad range of biological processes. Herein, we discuss the role of HINT1 as a regulator of several CNS functions, tumor suppressor, and mast cell activator via its interactions with multiple G-protein-coupled receptors and transcription factors. Importantly, altered HINT1 expression and mutation are connected to the progression of multiple disease states, including several neuropsychiatric disorders, peripheral neuropathy, and tumorigenesis. Additionally, due to its involvement in the activation of several clinically used phosphoramidate prodrugs, tremendous efforts have been made to better understand the interactions behind nucleoside binding and phosphoramidate hydrolysis by HINT1. We detail the substrate specificity and catalytic mechanism of HINT1 hydrolysis, while highlighting the structural biology behind these efforts. The aim of this review is to summarize the multitude of biological and pharmacological functions in which HINT1 participates while addressing the areas of need for future research.

Impact of Bmal1 Rescue and Time-Restricted Feeding on Liver and Muscle Proteomes During the Active Phase in Mice.

Molecular clocks and daily feeding cycles support metabolism in peripheral tissues. Although the roles of local clocks and feeding are well defined at the transcriptional level, their impact on governing protein abundance in peripheral tissues is unclear. Here, we determine the relative contributions of local molecular clocks and daily feeding cycles on liver and muscle proteomes during the active phase in mice. LC-MS/MS was performed on liver and gastrocnemius muscle harvested 4 h into the dark phase from WT, Bmal1 KO, and dual liver- and muscle-Bmal1-rescued mice under either ad libitum feeding or time-restricted feeding during the dark phase. Feeding-fasting cycles had only minimal effects on levels of liver proteins and few, if any, on the muscle proteome. In contrast, Bmal1 KO altered the abundance of 674 proteins in liver and 80 proteins in muscle. Local rescue of liver and muscle Bmal1 restored ∼50% of proteins in liver and ∼25% in muscle. These included proteins involved in fatty acid oxidation in liver and carbohydrate metabolism in muscle. For liver, proteins involved in de novo lipogenesis were largely dependent on Bmal1 function in other tissues (i.e., the wider clock system). Proteins regulated by BMAL1 in liver and muscle were enriched for secreted proteins. We found that the abundance of fibroblast growth factor 1, a liver secreted protein, requires BMAL1 and that autocrine fibroblast growth factor 1 signaling modulates mitochondrial respiration in hepatocytes. In liver and muscle, BMAL1 is a more potent regulator of dark phase proteomes than daily feeding cycles, highlighting the need to assess protein levels in addition to mRNA when investigating clock mechanisms. The proteome is more extensively regulated by BMAL1 in liver than in muscle, and many metabolic pathways in peripheral tissues are reliant on the function of the clock system as a whole.

Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.

Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI. Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018. We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.

The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community.

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.

Ion solvation as a predictor of lanthanide adsorption structures and energetics in alumina nanopores.

Adsorption reactions at solid-water interfaces define elemental fate and transport and enable contaminant clean-up, water purification, and chemical separations. For nanoparticles and nanopores, nanoconfinement may lead to unexpected and hard-to-predict products and energetics of adsorption, compared to analogous unconfined surfaces. Here we use X-ray absorption fine structure spectroscopy and operando flow microcalorimetry to determine nanoconfinement effects on the energetics and local coordination environment of trivalent lanthanides adsorbed on Al2O3 surfaces. We show that the nanoconfinement effects on adsorption become more pronounced as the hydration free energy, ΔGhydr, of a lanthanide decreases. Neodymium (Nd3+) has the least exothermic ΔGhydr (-3336 kJ·mol-1) and forms mostly outer-sphere complexes on unconfined Al2O3 surfaces but shifts to inner-sphere complexes within the 4 nm Al2O3 pores. Lutetium (Lu3+) has the most exothermic ΔGhydr (-3589 kJ·mol-1) and forms inner-sphere adsorption complexes regardless of whether Al2O3 surfaces are nanoconfined. Importantly, the energetics of adsorption is exothermic in nanopores only, and becomes endothermic with increasing surface coverage. Changes to the energetics and products of adsorption in nanopores are ion-specific, even within chemically similar trivalent lanthanide series, and can be predicted by considering the hydration energies of adsorbing ions.

Quantifying Atomically Dispersed Catalysts Using Deep Learning Assisted Microscopy.

The catalytic performance of atomically dispersed catalysts (ADCs) is greatly influenced by their atomic configurations, such as atom-atom distances, clustering of atoms into dimers and trimers, and their distributions. Scanning transmission electron microscopy (STEM) is a powerful technique for imaging ADCs at the atomic scale; however, most STEM analyses of ADCs thus far have relied on human labeling, making it difficult to analyze large data sets. Here, we introduce a convolutional neural network (CNN)-based algorithm capable of quantifying the spatial arrangement of different adatom configurations. The algorithm was tested on different ADCs with varying support crystallinity and homogeneity. Results show that our algorithm can accurately identify atom positions and effectively analyze large data sets. This work provides a robust method to overcome a major bottleneck in STEM analysis for ADC catalyst research. We highlight the potential of this method to serve as an on-the-fly analysis tool for catalysts in future in situ microscopy experiments.

Circadian transcriptome processing and analysis: a workflow for muscle stem cells.

Circadian rhythms coordinate biological processes with Earth's 24-h daily light/dark cycle. In the last years, efforts in the field of chronobiology have sought to understand the ways in which the circadian clock controls transcription across tissues and cells. This has been supported by the development of different bioinformatic approaches that allow the identification of 24-h oscillating transcripts. This workflow aims to describe how to isolate muscle stem cells for RNA sequencing analysis from a typical circadian experiment and introduces bioinformatic tools suitable for the analysis of circadian transcriptomes.

Integrating organizational climate theory: A domain-independent explanation for climate formation and function.

Organizational climate is arguably the most studied representation of the social context of organizations, having been examined as an antecedent, outcome, or boundary condition in virtually every domain of inquiry in the organizational sciences. Yet there is no commonly recognized, domain-independent theory that is used to explain why and how climates both form and affect behavior. Rather, there is a set of climate theories (and literatures) housed across a variety of divergent content domains. As a result, researchers who study climate in one domain are often unaware of climate advancements made in another. This lack of a theoretical lingua franca for climate limits our ability to understand what is known about climate and how climate research-whether domain-specific or domain-independent-can progress in a more cogent fashion. To resolve these fractures and unify climate scholarship, this article integrates existing theoretical perspectives of climate into a singular climate theory that summarizes and articulates domain-independent answers to the questions of why and how climates form and influence behavior in organizations. Using the individual drive to reduce uncertainty in meaningful social settings as the motivational mortar for this theoretical integration, we offer a needed reorientation to the field and illuminate a path forward for both future domain-specific and domain-independent climate advancements. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Liver and muscle circadian clocks cooperate to support glucose tolerance in mice.

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.