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The aim of this systematic review is to quantify potentially preventable patient harm from the frequency, severity, and preventability of the consequences and causes of surgical adverse events to help target patient safety improvement efforts. Two authors independently reviewed articles retrieved from systematic searches of the Cochrane library, MEDLINE, Embase, PsycINFO, and Cumulative Index to Nursing & Allied Health Literature databases for inclusion and exclusion criteria, methodology, and end points. All retrospective record review studies of adverse events were included. The primary end point was the frequency of general surgery adverse events. The secondary end points were the severity and preventability of consequences and causes. Fourteen record review studies incorporating 16,424 surgical patients were included. Adverse events occurred in 14.4% of patients (interquartile range [IQR], 12.5% to 20.1%), and potentially preventable adverse events occurred in 5.2% (IQR, 4.2% to 7.0%). The consequences of 3.6% of adverse events (IQR, 3.1% to 4.4%) were fatal, those of 10.4% (IQR, 8.5% to 12.3%) were severe, those of 34.2% (IQR, 29.2% to 39.2%) were moderate, and those of 52.5% (IQR, 49.8% to 55.3%) were minor. Errors in nonoperative management caused more frequent adverse events than errors in surgical technique.

Molecular interaction networks are a vital tool for studying biological systems. While many tools exist that visualize a protein or a pathway within a network, no tool provides the ability for a researcher to consider a protein’s position in a network in the context of a specific biological process or pathway. We developed ProteinWeaver, a web-based tool designed to visualize and analyze non-human protein interaction networks by integrating known biological functions. ProteinWeaver provides users with an intuitive interface to situate a user-specified protein in a user-provided biological context (as a Gene Ontology term) in seven model organisms. ProteinWeaver also reports the presence of physical and regulatory network motifs within the queried subnetwork and statistics about the protein’s distance to the biological process or pathway within the network. These insights can help researchers generate testable hypotheses about the protein’s potential role in the process or pathway under study. Two cell biology case studies demonstrate ProteinWeaver’s potential to generate hypotheses from the queried subnetworks. ProteinWeaver is available at https://proteinweaver.reedcompbio.org/ .

Background Vaccine hesitancy remains a significant public health concern despite the widespread availability of vaccines. Little is known about factors influencing hesitancy among U.S. military Veterans later in the pandemic. The goal of this study was to identify factors contributing to COVID-19 vaccine acceptance and hesitancy among U.S. military Veterans more than one year after vaccine availability. Methods This study was part of the COVID-19 Vaccine Acceptance Study (CoVAcS) conducted across ten Veterans Affairs Health Care Systems from February 2022 to April 2023. CoVAcS delivered motivational interviewing-informed training to healthcare providers and staff. Unvaccinated ( N  = 83) and recently vaccinated ( N  = 140) Veterans were surveyed using items from the Centers for Disease Control and Prevention Vaccine Confidence Survey. Univariable and multivariable logistic regression analyses were conducted. Results Compared to recently vaccinated Veterans in univariable analyses, unvaccinated Veterans were older, more likely female, reported higher household income, more likely from a rural residence, did not receive recent seasonal influenza vaccine, and were less likely to screen positive for anxiety or depression. Univariable results also demonstrated high levels of trust in VA healthcare providers and staff and in the VA healthcare system among unvaccinated and recently vaccinated Veterans. In addition, 67.5% of unvaccinated Veterans reported not having enough information about COVID vaccines. In multivariable analyses, unvaccinated Veterans were more likely to be female and live in a rural area. They were also less likely to believe the COVID-19 vaccine is safe, trust the seasonal flu vaccine, or screen positive for anxiety compared to recently vaccinated Veterans. Conclusions Results from this study suggest that demographic factors associated with Veteran vaccine hesitancy should be assessed over time to increase provider awareness and focus patient communication and outreach efforts. Unvaccinated Veterans indicated a need for more information about the COVID-19 vaccine. Autonomy-supportive and collaborative communication strategies such as motivational interviewing may help providers better understand patient perspectives on vaccine safety, as well as the barriers and potential benefits to vaccination. Trial registration ClinicalTrials.gov, TRN: NCT05027464, Registration Date: 30 August 2021.

Candida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However, Candida triggers a strong inflammatory response that, if not appropriately regulated, can damage host tissues. Therefore, it is important that the host immune response eliminates the fungus but limits tissue damage. This study provides evidence that targeting cholinergic receptors cannot only curb the virulence of C. albicans by inhibiting filamentous growth and biofilm formation but can also appropriately regulate the host immune response to induce rapid clearance with limited damage to vital tissues. This article provides evidence that repurposing licensed drugs that target cholinergic receptors may offer novel therapeutic solutions for the prevention or treatment of fungal infections. Acetylcholine modulates the virulence of Candida albicans and regulates an appropriate immune response to infection in a Galleria mellonella infection model. Indeed, the evidence suggests that C. albicans possesses a functional cholinergic receptor that can regulate filamentous growth and biofilm formation. Furthermore, G. mellonella immune cell subsets possess repertories of cholinergic receptors which regulate an effective and appropriate cellular immune response to C. albicans infection. This study aimed to investigate the cholinergic receptor subtype involved in regulation of filamentous growth and biofilm formation by C. albicans and determine the roles of cholinergic receptors in modulation of G. mellonella immune cell subsets. The general muscarinic receptor agonist, pilocarpine hydrochloride, inhibited C. albicans biofilm formation and pathogenicity, a phenomenon that could be reversed using the general muscarinic receptor antagonist, scopolamine. Pilocarpine hydrochloride protected G. mellonella larvae from C. albicans infection via inhibition of C. albicans filamentation and appropriate regulation of cellular immunity. However, scopolamine abrogated the capacity of pilocarpine hydrochloride to protect G. mellonella larvae from C. albicans infection. Furthermore, acetylcholine and pilocarpine hydrochloride exhibited differential modulatory capabilities on Galleria mellonella hemocyte responses to C. albicans . The data in this article demonstrate that a muscarinic receptor modulates C. albicans filamentation and biofilm formation. Furthermore, the results suggest that G. mellonella hemocyte subsets possess unique repertoires of cholinergic receptors that regulate their differentiation, activation, and function in contrasting manners. Therefore, targeting cholinergic receptors by repurposing currently licensed cholinergic drugs may offer novel therapeutic solutions for the prevention or treatment of fungal infections. IMPORTANCE Candida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However, Candida triggers a strong inflammatory response that, if not appropriately regulated, can damage host tissues. Therefore, it is important that the host immune response eliminates the fungus but limits tissue damage. This study provides evidence that targeting cholinergic receptors cannot only curb the virulence of C. albicans by inhibiting filamentous growth and biofilm formation but can also appropriately regulate the host immune response to induce rapid clearance with limited damage to vital tissues. This article provides evidence that repurposing licensed drugs that target cholinergic receptors may offer novel therapeutic solutions for the prevention or treatment of fungal infections.

Ward round skills are essential for the best management of surgical inpatients, but assessment of their quality has received inadequate attention. This study aims to design and validate the surgical ward round assessment tool (SWAT). We used modified Healthcare Failure Mode and Effects Analysis to develop the SWAT by identifying ward round steps. We assessed the validity of the SWAT using simulated and real surgical ward rounds. The Healthcare Failure Mode and Effects Analysis identified 30 ward round steps that were developed into the SWAT. Nineteen surgeons completed simulated surgical ward rounds. Eight fully trained surgeons scored significantly higher than 11 trainee surgeons when assessed with the SWAT (P = .001). On average, the participants thought the realism of the simulation was good. Forty-four surgeons completed real surgical ward rounds. Fifteen experts scored significantly higher than 29 trainee surgeons when assessed with SWAT (P = .001). Inter-rater reliability was .85 to .89, respectively. The SWAT can be used to assess the quality of task-based and nontechnical surgical ward round skills.

Background Integrating mental health providers into primary care clinics improves access to and outcomes of mental health care. In the Veterans Health Administration (VA) Primary Care Mental Health Integration (PCMHI) program, mental health providers are co-located in primary care clinics, but the implementation of this model is challenging outside large VA medical centers, especially for rural clinics without full mental health staffing. Long wait times for mental health care, little collaboration between mental health and primary care providers, and sub-optimal outcomes for rural veterans could result. Telehealth could be used to provide PCMHI to rural clinics; however, the clinical effectiveness of the tele-PCMHI model has not been tested. Based on evidence that implementation facilitation is an effective implementation strategy to increase uptake of PCMHI when delivered on-site at larger VA clinics, it is hypothesized that this strategy may also be effective with regard to ensuring adequate uptake of the tele-PCMHI model at rural VA clinics. Methods This study is a hybrid type 2 pragmatic effectiveness-implementation trial of tele-PCMHI in six sites over 24 months. Tele-PCMHI, which will be delivered by clinical staff available in routine care settings, will be compared to usual care. Fidelity to the care model will be monitored but not controlled. We will use the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework to evaluate the patient-level clinical effectiveness of tele-PCMHI in rural VA clinics and also to evaluate the fidelity to and outcomes of the implementation strategy, implementation facilitation. The proposed study will employ a stepped-wedge design in which study sites sequentially begin implementation in three steps at 6-month intervals. Each step will include (1) a 6-month period of implementation planning, followed by (2) a 6-month period of active implementation, and (3) a final period of stepped-down implementation facilitation. Discussion This study will evaluate the effectiveness of PCMHI in a novel setting and via a novel method (clinical video telehealth). We will test the feasibility of using implementation facilitation as an implementation strategy to deploy tele-PCMHI in rural VA clinics. Trial registration ClinicalTrials.gov registration number NCT02713217 . Registered on 18 March 2016

Background In the United States, discourse on COVID-19 vaccination has become polarized, and the positions of public health officials are met with skepticism by many vaccine-hesitant Americans. This polarization may impact future vaccination efforts as well as clinician-patient relationships. Methods We interviewed 77 vaccine-hesitant patients and 41 clinicians about COVID-19 vaccination communication in primary care as part of a Veterans Affairs (VA) trial evaluating a vaccine-communication intervention. This paper reports the findings of a qualitative analysis focused on one aspect of those interviews—the disconnect between primary care clinicians’ and patients’ perceptions about COVID-19 vaccination communication and decision-making. Results Rapid qualitative analysis of semi-structured interviews revealed fundamental differences in how clinicians and patients understood and described the reasoning, values, and concerns underlying COVID-19 vaccine hesitancy. These differences were significant and value-laden; they included negative judgments that could undermine communication between clinicians and patients and, over time, erode trust and empathy. Conclusion We advocate for empathic listening and suggest communication strategies to bridge the divide between clinicians and vaccine-hesitant patients.

Abstract Motivation Graphs are powerful tools for modeling and analyzing molecular interaction networks. Graphs typically represent either undirected physical interactions or directed regulatory relationships, which can obscure a particular protein’s functional context. Graphlets can describe local topologies and patterns within graphs, and combining physical and regulatory interactions offer new graphlet configurations that can provide biological insights. Results We present GRPhIN, a tool for characterizing graphlets and protein roles within graphlets in mixed physical and regulatory interaction networks. We describe the graphlets of mixed networks in Bacillus subtilis, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, and Saccharomyces cerevisiae and examine local topologies of proteins and subnetworks related to the oxidative stress response pathway. We found a number of graphlets that were abundant in all species, specific node positions (orbits) within graphlets that were overrepresented in stress-associated proteins, and rarely-occurring graphlets that were overrepresented in oxidative stress subnetworks. These results showcase the potential for using graphlets in mixed physical and regulatory interaction networks to identify new patterns beyond a single interaction type. Availability and implementation GRPhIN is available at https://github.com/Reed-CompBio/grphin.

The global utilization of single-use, non-biodegradable plastics, such as bottles made of polyethylene terephthalate (PET), has contributed to catastrophic levels of plastic pollution. Fortunately, microbial communities are adapting to assimilate plastic waste. Previously, our work showed a full consortium of five bacteria capable of synergistically degrading PET. Using omics approaches, we identified the key genes implicated in PET degradation within the consortium’s pangenome and transcriptome. This analysis led to the discovery of a novel PETase, EstB, which has been observed to hydrolyze the oligomer BHET and the polymer PET. Besides the genes implicated in PET degradation, many other biodegradation genes were discovered. Over 200 plastic and plasticizer degradation-related genes were discovered through the Plastic Microbial Biodegradation Database (PMBD). Diverse carbon source utilization was observed by a microbial community-based assay, which, paired with an abundant number of plastic- and plasticizer-degrading enzymes, indicates a promising possibility for mixed plastic degradation. Using RNAseq differential analysis, several genes were predicted to be involved in PET degradation, including aldehyde dehydrogenases and several classes of hydrolases. Active transcription of PET monomer metabolism was also observed, including the generation of polyhydroxyalkanoate (PHA)/polyhydroxybutyrate (PHB) biopolymers. These results present an exciting opportunity for the bio-recycling of mixed plastic waste with upcycling potential.