Effect of General Surgery Resident Participation in Thoracic Surgery on Oncologic Outcomes: An Observational Cohort Study.

Background: Despite increasing sub-specialization, general surgeons continue to perform oncologic thoracic surgeries. Our objective was to determine whether general surgery resident participation in thoracic surgery affects surgical quality or oncologic outcomes. We hypothesized that patient outcomes with and without resident participation would be similar. Methods: We retrospectively reviewed the electronic health records of patients with stage 0-IV lung cancer undergoing oncologic pulmonary resection at BLINDED FOR REVIEW during an 11-year period (2012-2022). Patients younger than 18 years or older than 85 years were excluded, as were those who had incomplete follow-up data or were unregistered in our institutional cancer registry. Patients were divided into groups based on whether residents or staff surgeons completed >50% of the critical portions of the operation. We compared 30-day morbidity outcomes, overall survival (OS), and disease-free survival (DFS). Results: Three hundred thirteen patients met inclusion criteria. Demographic and clinical characteristics were similar between groups, as were types of surgical resection and median operative times. A statistical difference was found in the distribution of surgical approach. The odds of morbidity were 65% higher in the Staff group (OR=1.65; 95% CI, 1.007-2.71). Resident participation was not significantly associated with OS or DFS (P =.32 and P =.54, respectively). Discussion: General surgery resident involvement in lung cancer operations is not associated with longer operative times but is associated with a higher likelihood of a thoracotomy. General surgery resident involvement was associated with decreased postoperative morbidity and did not significantly affect OS or DFS.

Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200 µmol/kg, IV), worsens the adverse actions of fentanyl (75 µg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.

Generalized genetic liability to substance use disorders.

Lifetime and temporal co-occurrence of substance use disorders (SUDs) is common and compared with individual SUDs is characterized by greater severity, additional psychiatric comorbidities, and worse outcomes. Here, we review evidence for the role of generalized genetic liability to various SUDs. Coaggregation of SUDs has familial contributions, with twin studies suggesting a strong contribution of additive genetic influences undergirding use disorders for a variety of substances (including alcohol, nicotine, cannabis, and others). GWAS have documented similarly large genetic correlations between alcohol, cannabis, and opioid use disorders. Extending these findings, recent studies have identified multiple genomic loci that contribute to common risk for these SUDs and problematic tobacco use, implicating dopaminergic regulatory and neuronal development mechanisms in the pathophysiology of generalized SUD genetic liability, with certain signals demonstrating cross-species and translational validity. Overlap with genetic signals for other externalizing behaviors, while substantial, does not explain the entirety of the generalized genetic signal for SUD. Polygenic scores (PGS) derived from the generalized genetic liability to SUDs outperform PGS for individual SUDs in prediction of serious mental health and medical comorbidities. Going forward, it will be important to further elucidate the etiology of generalized SUD genetic liability by incorporating additional SUDs, evaluating clinical presentation across the lifespan, and increasing the granularity of investigation (e.g., specific transdiagnostic criteria) to ultimately improve the nosology, prevention, and treatment of SUDs.

Re-assessing viologens for modern bio-electrocatalysis.

Viologens, 1,1'-disubstituted-4,4'-bipyridinium salts, are organic redox species that can be used in place of NADPH as mediators for redox enzymes. In this study, using the reduction of oxidized glutathione by glutathione reductase as a model system, a rationally designed library of viologens covering a range of polarities and functional groups were explored as electron transfer mediators for bio-electrocatalysis. Through a series of electrochemical investigations, the reduction potential was found to be the primary determining factor for electron transfer between the viologen and enzyme. Through enhancing the solubility of viologen such that the fully reduced state remained soluble, we demonstrate a much-widened window of useable viologen potentials. In doing so, we describe for the first time a highly efficient electron transfer to a flavoenzyme promoting the catalytic reaction in the absence of co-factors. As such, our study provides a platform for broadening the scope for using viologens as mediating agents for electrochemically-driven enzymatic processes.

Gut microbial features and dietary fiber intake predict gut microbiota response to resistant starch supplementation.

Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a 7-week crossover study with 59 individuals completing the study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and digestible starch, for 10 d each with 5-d washout periods in between. We collected fecal and saliva samples and food records during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase (AMY1) gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of the relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. AMY1-related metrics were not predictive of response to RS. SAA was only predictive of the relative abundance of one ASV after digestible starch supplementation. Interestingly, SCFA concentrations increased the most during digestible starch supplementation. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation because these data can be used to predict changes in specific ASVs and fecal SCFA concentrations. These findings lay a foundation to support the premise that using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.

Genetic risk for trait aggression and alcohol use predict unique facets of alcohol-related aggression.

OBJECTIVE: A propensity for aggression or alcohol use may be associated with alcohol-related aggression. Previous research has shown genetic overlap between alcohol use and aggression but has not looked at how alcohol-related aggression may be uniquely influenced by genetic risk for aggression or alcohol use. The present study examined the associations of genetic risk for trait aggression, alcohol use, and alcohol use disorder (AUD) with alcohol-related aggression using a polygenic risk score (PRS) approach. METHOD: Using genome-wide association study summary statistics, PRSs were created for trait aggression, alcohol consumption, and AUD. These PRSs were used to predict the phenotype of alcohol-related aggression among drinkers in two independent samples: the University of California at San Francisco (UCSF) Family Alcoholism Study (n = 1,162) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,291). RESULTS: There were significant associations between the AUD PRS and lifetime alcohol-related aggression in the UCSF study sample. Additionally, the trait aggression PRS was associated with three or more experiences of hitting anyone else and getting into physical fights while under the influence of alcohol, along with a composite score of three or more experiences of alcohol-related aggression, in the UCSF study sample. No significant associations were observed in the Add Health sample. Limited sex-specific genetic effects were observed. CONCLUSIONS: These results provide preliminary evidence that genetic influences underlying alcohol use and aggression are uniquely associated with alcohol-related aggression and suggest that these associations may differ by type and frequency of alcohol-related aggression incidents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Carbazole-embedded p-benziporphyrinoid: synthesis, structure and a reversible chemodosimeter for mercury(II) ions.

The first carbazole-embedded p-benziporphyrinoid is synthesized by a [3+1] acid-catalyzed condensation between appropriate coupling partners. The macrocycle 1 exhibited orange emission and showed a large Stokes shift of 5831 cm-1. Intriguingly, it shows a selective affinity towards Hg2+ ions over other metal-ions in a reversible manner. Job's plot confirmed the 1 : 1 stoichiometry with unambiguous confirmation of both 1 and 1-Hg by single crystal X-ray analysis.

Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Determinants of mosaic chromosomal alteration fitness.

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.

Advanced Critical Care Techniques in the Field.

Critical care principles and techniques continue to hold promise for improving patient outcomes in time-dependent diseases encountered by emergency medical services such as cardiac arrest, acute ischemic stroke, and hemorrhagic shock. In this review, the authors discuss several current and evolving advanced critical care modalities, including extracorporeal cardiopulmonary resuscitation, resuscitative endovascular occlusion of the aorta, prehospital thrombolytics for acute ischemic stroke, and low-titer group O whole blood for trauma patients. Two important critical care monitoring technologies-capnography and ultrasound-are also briefly discussed.

A Multimodal Exertional Test for concussion: a pilot study in healthy athletes.

Introduction: Exertional tests have become a promising tool to assist clinicians in the management of concussions, however require expensive equipment, extensive spaces, and specialized clinician expertise. As such, we developed a test with minimal resource requirements encompassing key elements of sport and physical activity. The purpose of this study was to pilot test the Multimodal Exertional Test (MET) protocol in a sample of healthy interuniversity athletes. Methods: The MET comprises four stages, each featuring three distinct tasks. The test begins with engaging in squats, alternating reverse lunges, and hip hinges (Stage 1). The next stage progressively evolves into executing these tasks within specified time limits (Stage 2). Following this, the test advances to a stage that incorporates cognitive tasks (Stage 3), and the final stage demands greater levels of physical exertion, cognition, and multi-directional movements (Stage 4). Heart rate (HR) was obtained during each stage of the MET and participants' symptom severity scores were recorded following each task. Results: Fourteen healthy interuniversity athletes (n = 8 female, n = 6 male) participated in the study. HR was obtained for 10 of the 14 athletes (females: n = 6, males: n = 4). Increases in average and maximum HR were identified between pre-MET and Stage 1, and between Stages 3 and 4. Consistent with the tasks in each stage, there were no increases in average and maximum HR observed between MET Stages 1 to 3. Female athletes exhibited higher average and maximum HRs compared to male athletes during all four stages. All 14 athletes reported minimal changes in symptom severity following each task. Conclusion: Among healthy athletes, the MET elicits an increase in average and maximum HR throughout the protocol without symptom provocation. Female athletes exhibit higher HRs during all four stages in comparison to male athletes.

Reactivity of amino acids and short peptide sequences: identifying bioactive compounds via DFT calculations.

Bioactive peptides are short amino acid sequences that play important roles in various physiological processes, including antioxidant and protective effects. These compounds can be obtained through protein hydrolysis and have a wide range of potential applications in a variety of areas. However, despite the potential of these compounds, more in-depth knowledge is still necessary to better understand details regarding their chemical reactivity and electronic properties. In this study, we used molecular modeling techniques to investigate the electronic structure of isolated amino acids (AA) and short peptide sequences. Details on the relative alignments between the frontier electronic levels, local chemical reactivity and donor-acceptor properties of the 20 primary amino acids and some di- and tripeptides were evaluated in the framework of the density functional theory (DFT). Our results suggest that the electronic properties of isolated amino acids can be used to interpret the reactivity of short sequences. We found that aromatic and charged amino acids, as well as Methionine, play a key role in determining the local reactivity of peptides, in agreement with experimental data. Our analyses also allowed us to identify the influence of the relative position of AA and terminations on the local reactivity of the sequences, which can guide experimental studies and help to propose/evaluate possible mechanisms of action. In summary, our data indicate that the position of active sites of polypeptides can be predicted from short sequences, providing a promising strategy for the synthesis and bioprospection of new optimized compounds.

Improved corneal clarity following lamellar keratectomy for corneal lipidosis in a canine with ocular manifestations of hypothyroidism.

OBJECTIVE: To report the corneal clarity outcome following lamellar keratectomy of arcus lipoides corneae secondary to canine hypothyroidism and report a unique retinal manifestation of systemic disease. ANIMAL STUDIED: Four-year-old spayed female Sheepdog-Poodle canine. PROCEDURE: Lamellar keratectomy OD. RESULTS: Bilateral severe arcus lipoides corneae was noted in the initial presentation. Bilateral, symmetric, and multifocal bullous retinal detachments were observed at subsequent visits. Biochemical testing revealed hyperlipidemia presumed to be associated with primary acquired thyroiditis. Corneal clarity and visual behaviors were significantly improved following unilateral lamellar keratectomy with no evidence of recurrence within the year following surgery. Bilateral retinal detachments and hyperlipidemia resolved months after initiation of thyroxine supplementation. Corneal lipidosis in the untreated eye remained static. CONCLUSIONS: Lamellar keratectomy is a viable surgical option for the treatment of arcus lipoides corneae. Hypothyroidism should be considered a differential diagnosis for spontaneous, bilateral, multifocal, and serous retinal detachments.

A randomized trial to compare smooth monofilament suture vs. barbed suture using the three-layer continuous closure technique in canine ovariohysterectomy in a high-quality high-volume spay/neuter clinic.

The primary objective of this study was to compare time efficiency and complication rates between smooth monofilament suture (SMS) and barbed suture (BS) using the three-layer continuous incisional closure pattern after ovariohysterectomy in a high-quality high-volume spay/neuter clinic. The study was designed as a randomized controlled trial enrolling 71 adult female dogs. Dogs were randomly assigned to SMS or BS treatments. The effect of closure with BS or SMS on closure time was tested through multilevel, multivariable linear regression in a generalized linear mixed model. Body condition score, weight, and pre-closure incision length were tested as covariates. Surgeon was included in the model as a random effect. Pre-closure incision length (p = 0.01) and method (p ≤ 0.0001) were associated with closure time. Adjusting for pre-closure incision length, the average time for closure with SMS was 6.5 min (range 3.70-10.31 min), and the average time for closure with BS was 4.91 min (range 3.05-8.05 min). Accounting for the closure method, the closure time increased by 39 s for each additional centimeter of incision length. BS was more efficient than SMS when performing the three-layer continuous suture pattern. No short-term telemedicine-assessed complications were noted with either treatment method. BS can improve efficiency in surgical closures, especially considering large volumes of animals, and appears to have a similar short-term, telemedicine-assessed complication rate when compared to SMS.

Thermally Robust Solvent-Free Liquid Polyplexes for Heat-Shock Protection and Long-Term Room Temperature Storage of Therapeutic Nucleic Acids.

Nucleic acid therapeutics have attracted recent attention as promising preventative solutions for a broad range of diseases. Nonviral delivery vectors, such as cationic polymers, improve the cellular uptake of nucleic acids without suffering the drawbacks of viral delivery vectors. However, these delivery systems are faced with a major challenge for worldwide deployment, as their poor thermal stability elicits the need for cold chain transportation. Here, we demonstrate a biomaterial strategy to drastically improve the thermal stability of DNA polyplexes. Importantly, we demonstrate long-term room temperature storage with a transfection efficiency maintained for at least 9 months. Additionally, extreme heat shock studies show retained luciferase expression after heat treatment at 70 °C. We therefore provide a proof of concept for a platform biotechnology that could provide long-term room temperature storage for temperature-sensitive nucleic acid therapeutics, eliminating the need for the cold chain, which in turn would reduce the cost of distributing life-saving therapeutics worldwide.

Trends of Self-Inflicted Firearm Injuries at a Rural Level 1 Trauma Center.

Firearm injuries are a major public health concern with much focus on injuries due to violent crimes in urban areas. Less focus has been on self-inflicted injuries and rural settings. This study included 201 patients, of which 124 (61.7%) were accidental and 77 (38.3%) were intentional self-inflicted gunshot wounds (GSWs) sustained over 6 years at a rural level 1 trauma center. Injury severity scores (P < .001), hospital days (P < .001), and mortality (P < .001) were significantly higher among intentional self-inflicted GSWs. Injuries to the head were the most common injury among patients with intentional self-inflicted GSWs (P < .001).Accidental and intentional self-inflicted GSWs make up a large portion of firearm injuries seen at our rural level 1 trauma center, and defining these injuries can facilitate the need for targeted gun safety and injury prevention efforts.