Understanding the role of negative charge in the scaffold of an artificial enzyme for CO2 hydrogenation on catalysis.

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [RhI(PEt2NglyPEt2)2]-. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere. Placing a negative charge in the secondary or outer coordination sphere demonstrates decreased activity by a factor of two compared to the wild-type Rh-LmrR. Interestingly, addition of positive charge in the secondary sphere, with the negatively charged outer coordination sphere restores activity. Vibrational and NMR spectroscopy suggest minimal changes to the electronic density at the rhodium center, regardless of inclusion of a negative or positive charge in the secondary sphere, suggesting another mechanism is impacting catalytic activity, explored in the discussion.

The Use of Telehealth to Improve Office Efficiency and Health Care Access Among Patients Being Evaluated for Revision Total Joint Arthroplasty.

BACKGROUND: Patients being evaluated for revision total joint arthroplasty (RTJA) are often referred to tertiary care centers, which may decrease their access to adequate health care and overburden these health care systems. The purpose of this study was to evaluate the feasibility and effectiveness of RTJA patient evaluation via telehealth. MATERIALS AND METHODS: We identified a consecutive series of patients newly evaluated for a symptomatic TJA by two academic surgeons during a 1-year period. Clinical records, radiographs, and laboratory values were reviewed to determine whether the patient was indicated for RTJA. Efficiency was determined by calculating the percentage of patients who could have been adequately evaluated with telehealth. We then used the modalities required for diagnosis in each RTJA case to determine the feasibility of evaluating such patients through telehealth. RESULTS: Of the 381 patients evaluated for RTJA candidacy, 154 (40.4%) were indicated for revision surgery. All 152 patients evaluated for possible hip revision could have been evaluated and diagnosed via telehealth, demonstrating a telehealth efficiency of 100%. Of 229 patients evaluated for possible knee revision, 183 were able to be evaluated and diagnosed via telehealth. The 46 remaining patients were indicated for revision secondary to instability, which would require an in-office examination for diagnosis. The efficiency of telehealth for potential knee revision patients was 79.9%. CONCLUSION: Telehealth may be useful in evaluating patients with symptomatic TJA. It may increase the efficiency of in-office evaluations and reduce potential barriers to health care access. [Orthopedics. 202x;4x(x):xx-xx.].

Developing Proficiency in Robotic Cardiac Surgery.

The purpose of this manuscript is to provide recommendations for cardiac surgeons interested in adopting a robotic platform into their programs. The recommendations are based on the experience of the authors and cover a diverse array of cardiac surgical procedures that are currently being performed with robotic assistance. The focus, as with any innovative surgical approach, is to ensure patient safety, maximize quality and efficacy, and to set realistic expectations about what is required to achieve proficiency in robotic cardiac surgery.

The small acid-soluble proteins of Clostridioides difficile regulate sporulation in a SpoIVB2-dependent manner.

Clostridioides difficile is a pathogen whose transmission relies on the formation of dormant endospores. Spores are highly resilient forms of bacteria that resist environmental and chemical insults. In recent work, we found that C. difficile SspA and SspB, two small acid-soluble proteins (SASPs), protect spores from UV damage and, interestingly, are necessary for the formation of mature spores. Here, we build upon this finding and show that C. difficile sspA and sspB are required for the formation of the spore cortex layer. Moreover, using an EMS mutagenesis selection strategy, we identified mutations that suppressed the defect in sporulation of C. difficile SASP mutants. Many of these strains contained mutations in CDR20291_0714 (spoIVB2) revealing a connection between the SpoIVB2 protease and the SASPs in the sporulation pathway. This work builds upon the hypothesis that the small acid-soluble proteins can regulate gene expression.

Outcomes of Adults With Unrepaired Partial Anomalous Pulmonary Venous Return and Intact Atrial Septum.

BACKGROUND: The purpose of this study was to describe the correlates and outcomes in adults with unrepaired partial anomalous pulmonary venous return and intact atrial septum (PAPVR-IAS). METHODS AND RESULTS: We identified adults with PAPVR-IAS who received care at the Mayo Clinic, while those with unrepaired PAPVR-IAS comprised the reference group. Clinical indices (New York Heart Association class, peak oxygen consumption, and NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and echo-derived right heart indices (right atrial [RA] volume, RA reservoir strain, right ventricular [RV] free wall strain, RV end-diastolic area, and RV systolic pressure) were assessed at baseline and 3-year and 5-year follow-up. There were 80 patients and 38 patients with unrepaired versus repaired PAPVR-IAS, respectively. The clinical predictors of surgical repair were the number of anomalous veins, RA volume, and RV end-diastolic area. The PAPVR-IAS risk score, derived from these clinical predictors, was associated with surgical repair (adjusted odds ratio, 1.37 [95% CI, 1.24-1.65] per unit increase in risk score; area under the curve, 0.742). Among patients with unrepaired PAPVR-IAS with 3-year (n=73) and 5-year follow-up (n=36), there was no temporal change in clinical indices (New York Heart Association class, predicted peak oxygen consumption, and NT-proBNP) and right heart indices (RA volume index, RA reservoir strain, RV end-diastolic area index, RV free wall strain, and RV systolic pressure). CONCLUSIONS: The PAPVR-IAS risk score can be used to assess the odds of requiring surgical repair. Furthermore, there was no temporal deterioration in clinical and right heart indices during follow-up in adults with unrepaired PAPVR-IAS.

A multi-center evaluation of a novel IVF cryostorage device in an active clinical setting.

The objective of this study was to evaluate the function, and usability of a novel automated software-guided cryostorage system in an active IVF laboratory setting. The investigational device (ID) was installed at 3 IVF laboratories (sites: α, ß, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of mock patient specimens by the ID were evaluated. To assess an LN2 pressure builder, the frequency of use and events of workflow interruption were logged. Student's t-test was used to determine statistical significance. The ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean ± SD temperatures during active use were: α, - 176.57 ± 1.83 °C; ß, - 178.21 ± 2.75 °C; γ, - 178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, - 165.14 °C; ß, - 157.41 °C; γ, - 164.45 °C. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no mock specimen was exposed to a detrimental (> - 150 °C) temperature excursion. Over the 25 LN2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN2 pressure. The ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be integrated into active IVF laboratories.

Effects of Adjuvant Endocrine Therapy-Specific Perceptions on Response to a Behavioral Intervention for Adjuvant Endocrine Therapy Adherence in Patients With Breast Cancer.

PURPOSE: Adjuvant endocrine therapy (AET) is a life-saving medication for patients with hormone-sensitive breast cancer, yet many struggle with adherence, warranting behavioral intervention. In our recent trial, participation in a group cognitive behavioral intervention (STRIDE) for symptom management and adherence was associated with improvements in symptom distress, coping, quality of life, and mood. We now explore whether baseline patient- and medication-specific factors-which may be modifiable by clinician-led discussions-moderated the effect of STRIDE on adherence rates. METHODS: From October 2019 to June 2021, 100 patients with early-stage breast cancer reporting AET-related distress were enrolled and randomly assigned to STRIDE or a medication monitoring (MM) control group. All patients stored their AET in electronic pill bottles to track objective adherence. Patients also self-reported their adherence on the Medication Adherence Report Scale-5 and their perceptions of AET on the Cancer Therapy Satisfaction Questionnaire at baseline. We conducted hierarchical linear modeling to test moderators of intervention effects on objective adherence rates. We report the time × group × moderator effects. RESULTS: Among patients reporting greater perceived difficulties with AET adherence at baseline, STRIDE participants had higher adherence rates over time compared with MM (b = -13.80; SE = 4.56; P < .01). Patients with greater expectations of therapeutic benefit from AET also had improved adherence rates if they were assigned to STRIDE, versus MM (b = 0.25; SE = 0.10; P = .01). Patients who perceived taking AET as convenient and had been taking their AET for less time had higher adherence rates in STRIDE, versus MM. CONCLUSION: The current study identified patient- and medication-specific factors that may augment AET adherence interventions and may be modifiable through clinician-led discussions, such as perceptions of adherence problems, therapeutic efficacy, and convenience of AET.

Rheumatoid arthritis is associated with higher 90-day systemic complications compared to osteoarthritis after total shoulder arthroplasty: a cohort study.

Background: Total shoulder arthroplasty (TSA) in patients with rheumatoid arthritis (RA) can present unique challenges. The aim of this study was to compare both systemic and joint-related postoperative complications in patients undergoing primary TSA with RA versus those with primary osteoarthritis (OA). Methods: Using the TriNetX database, Current Procedural Terminology and International Classification of Diseases, 10th edition codes were used to identify patients who underwent primary TSA. Patients were categorized into two cohorts: RA and OA. After 1:1 propensity score matching, postoperative systemic complications within 90 days following primary TSA and joint-related complications within 5 years following anatomic TSA (aTSA) and reverse shoulder arthroplasty (RSA) were compared. Results: After propensity score matching, the RA and OA cohorts each consisted of 8,523 patients. Within 90 days postoperation, RA patients had a significantly higher risk of total complications, deep surgical site infection, wound dehiscence, pneumonia, myocardial infarction, acute renal failure, urinary tract infection, mortality, and readmission compared to the OA cohort. RA patients had a significantly greater risk of periprosthetic joint infection and prosthetic dislocation within 5 years following aTSA and RSA, and a greater risk of scapular fractures following RSA. Among RA patients, RSA had a significantly higher risk of prosthetic dislocation, scapular fractures, and revision compared to aTSA. Conclusions: Following TSA, RA patients should be considered at higher risk of systemic and joint-related complications compared to patients with primary OA. Knowledge of the risk profile of RA patients undergoing TSA is essential for appropriate patient counseling and education. Level of evidence: III.

The impact of mental health on shoulder arthroplasty and rotator cuff repair: a meta-analysis.

Background: The aim of this study was to evaluate the impact of mental health attributes, such as the presence of psychiatric comorbidities or psychological comorbidities (low resilience), on outcomes after rotator cuff repair (RCR) and total shoulder arthroplasty (TSA). Methods: PubMed, Cochrane, and Google Scholar (results pages 1-20) were searched up to November 2023. Mental health problems of interest included the presence of psychiatric comorbidities (depression, anxiety) or indicators of poor psychological functioning, such as low resilience or the presence of distress. Patients were assigned to poor or good mental health groups in this study based on their grouping in the original study. Results: Fourteen studies were included in the meta-analysis. Patients with good mental health had greater improvements in postoperative American Shoulder and Elbow Surgeons and Simple Shoulder Test scores in the TSA cohort (P=0.003 and P=0.01), RCR cohort (P<0.001), and the combined TSA and RCR cohort (P<0.001). No difference was found in visual analog scale score, satisfaction, external rotation, or flexion between the two mental health groups. Patients with poor mental health undergoing RCR experienced higher rates of adverse events and transfusions (P<0.001). Patients with poor mental health also had greater rates of revision and emergency department visits in the TSA cohort (P<0.001), RCR cohort (P=0.05 and P=0.03), and combined cohort (P<0.001). Patients with poor mental health undergoing TSA had a higher rate of re-admission (P<0.001). Conclusions: Patients with poor preoperative mental health showed inferior patient-reported outcome scores and increased rates of adverse events, revisions, and re-admissions.

The role of vitamin D in shoulder health: a comprehensive review of its impact on rotator cuff tears and surgical results.

Vitamin D deficiency is highly prevalent in the general population and is associated with various chronic health conditions. In addition to its role in bone mineralization, Vitamin D has various physiological effects that may impact the pathogenesis of shoulder pathologies. Vitamin D deficiency may also affect outcomes after shoulder surgeries, such as rotator cuff repair and total shoulder arthroplasty. Vitamin D plays a role in tissue healing, bone growth, and maintenance of homeostasis in skeletal muscle cells. Vitamin D also has anti-inflammatory effects that are important to rotator cuff health. Vitamin D deficiency is highly prevalent in patients with rotator cuff tears, suggesting its role as a potential risk factor. Vitamin D deficiency has been associated with decreased preoperative shoulder strength as well as increased re-tear rates, postoperative stiffness, and the need for revision surgery in patients who underwent rotator cuff repair. Studies have also demonstrated a potential association between vitamin D deficiency and increased risk of revision after total shoulder arthroplasty. Further research is necessary to elucidate the direct role of vitamin D in the pathogenesis of rotator cuff tears and its impact on clinical outcomes after rotator cuff surgery and total shoulder arthroplasty.

Reverse Versus Anatomic Total Shoulder Arthroplasty for Glenohumeral Osteoarthritis with Intact Cuff: A Meta-Analysis of Clinical Outcomes.

BACKGROUND: Anatomic and reverse shoulder arthroplasty (TSA, RSA) have surged in popularity in recent years. While RSA is Food and Drug Administration (FDA) approved for cases of rotator cuff tear arthropathy, indications have expanded to include, among others, primary glenohumeral osteoarthritis (GHOA). METHODS: PubMed, Cochrane, and Google Scholar (pages 1-20) were queried through November 2023. Inclusion criteria consisted of studies that compared the utility of TSA to that of RSA for the treatment of GHOA with intact rotator cuff with respect to adverse events, patient-reported outcomes, and range of motion. The ROBINS-I tool was used to assess the risk of bias in the included non-randomized studies, and Review Manager 5.4 was used for statistical analysis. P-values <0.05 were deemed significant. RESULTS: Fourteen studies met the above inclusion criteria. Twelve studies reported adverse outcomes, with the RSA group having a lower rate of complications (odds-ratio=0.54, p=0.004) and reoperations (odds-ratio=0.31, p<.001) relative to TSA at an average follow-up of 3.4 years. Four studies reported SPADI and UCLA scores, while five reported SST scores. These studies showed superior SPADI (p=0.040), UCLA(p=0.006), and SST(p=0.040) scores among the RSA group. No significant differences were seen with regards to other patient reported outcomes. Ten studies reported on range of motion, and the RSA group had a significantly lower external rotation relative to the TSA group (p<.001) while other range of motion parameters did not show statistically significant differences. CONCLUSION: The present study provides support for RSA as a reasonable surgical option for patients with GHOA and an intact rotator cuff, with lower rates of adverse events and better outcomes relative to TSA, although at the expense of decreased external rotation. Patient education and counseling is key in order to decide optimal treatment as part of a shared decision-making process, as well as setting appropriate expectations.

Gluten dependent activation of CD4+ T cells by MHC class II-expressing epithelium.

BACKGROUND AND AIMS: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T cell interactions in organoid monolayers expressing human MHC class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. METHODS: Epithelial MHC class II (MHCII) was determined in active and treated CeD, and in non-immunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without IFN-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T cell co-cultures were incubated with gluten, pre-digested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. RESULTS: Active CeD patients and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer-T cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T cell activation markers, and the release of IL-2, IFN-γ, and IL-15 in co-culture supernatants. Gluten metabolized by P. aeruginosa, but not the lasB mutant, enhanced CD4+ T cell proliferation and activation. CONCLUSIONS: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten pre-digestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in CeD patients.

Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score.

We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.

Effects of Weight Loss and Weight Maintenance on Lipoprotein Insulin Resistance Scores in Adults with Overweight and Obesity.

Background: An elevated lipoprotein insulin resistance (LP-IR) score corresponds to insulin resistance in adults with overweight and obesity, yet data are lacking regarding the impact of exercise interventions on LP-IR. The purpose of this secondary analysis was to evaluate the effects of a weight loss and weight maintenance intervention on LP-IR score in adults with overweight and obesity. Methods: Thirty sedentary adults with overweight and obesity completed a 10-week OPTIFAST® weight loss program with supervised aerobic exercise to achieve clinical weight loss (CWL) (≥7% from baseline). Aerobic exercise volume increased weekly until 700 MET min/week was reached. Participants who reached CWL were randomized to groups at volumes at either physical activity (PA-REC) or weight maintenance (WM-REC) recommendations (weeks 11-28). Plasma blood samples were analyzed via nuclear magnetic resonance spectroscopy at baseline, after weight loss (week 10), and following weight maintenance (week 28). Results: Following the weight loss phase, on average, participants significantly (p < 0.001) reduced LP-IR score (-12.1 ± 13.5), body weight (-8.9 ± 2.7%), and waist circumference (-7.7 ± 4.1 cm). During the weight maintenance phase, there were no changes in LP-IR score between exercise groups (PA-REC: 4.1 ± 13.6; WM-REC: -2.0 ± 11.2; P = 0.7). The PA-REC group had improvements in LP-IR score from baseline (49.8 ± 24.6 to 36.6 ± 27.6, P < 0.001), yet there were no within-group changes during the weight maintenance phase (P > 0.05). Conclusion: LP-IR score improved during weight loss in adults with overweight and obesity and were sustained during the weight maintenance phase in the PA-REC group. Aerobic exercise at least at minimum guidelines following CWL can preserve LP-IR score improvements and may indicate a reduced T2DM risk in adults with overweight and obesity.

Proteome-scale prediction of molecular mechanisms underlying dominant genetic diseases.

Many dominant genetic disorders result from protein-altering mutations, acting primarily through dominant-negative (DN), gain-of-function (GOF), and loss-of-function (LOF) mechanisms. Deciphering the mechanisms by which dominant diseases exert their effects is often experimentally challenging and resource intensive, but is essential for developing appropriate therapeutic approaches. Diseases that arise via a LOF mechanism are more amenable to be treated by conventional gene therapy, whereas DN and GOF mechanisms may require gene editing or targeting by small molecules. Moreover, pathogenic missense mutations that act via DN and GOF mechanisms are more difficult to identify than those that act via LOF using nearly all currently available variant effect predictors. Here, we introduce a tripartite statistical model made up of support vector machine binary classifiers trained to predict whether human protein coding genes are likely to be associated with DN, GOF, or LOF molecular disease mechanisms. We test the utility of the predictions by examining biologically and clinically meaningful properties known to be associated with the mechanisms. Our results strongly support that the models are able to generalise on unseen data and offer insight into the functional attributes of proteins associated with different mechanisms. We hope that our predictions will serve as a springboard for researchers studying novel variants and those of uncertain clinical significance, guiding variant interpretation strategies and experimental characterisation. Predictions for the human UniProt reference proteome are available at https://osf.io/z4dcp/.

Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. REGISTRATION: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.

Timing of diffusion tensor imaging in the management of a ruptured pediatric arteriovenous malformation: illustrative case.

BACKGROUND: Diffusion tensor imaging (DTI) can characterize eloquent white matter tracts affected by brain arteriovenous malformations (AVMs). However, DTI interpretation can be difficult in ruptured cases due to the presence of blood products. The authors present the case of a ruptured pediatric AVM in the corticospinal tract (CST) and discuss how DTI at different time points informed the treatment. OBSERVATIONS: A 9-year-old female presented with a sudden headache and left hemiparesis. She was found to have a Spetzler-Martin grade III, Supplementary grade I AVM in the right caudate and centrum semiovale, with obliteration and corresponding reduced fractional anisotropy (FA), fiber density (FD), and tract count (TC) of the adjacent CST on DTI. The patient remained stable and was scheduled for elective resection following a 6-week period to facilitate hematoma resorption. After 6 weeks, repeat DTI showed part of the nidus within intact CST fibers with concordant improvement in FA, FD, and TC. Considering the nidus location, CST integrity, and motor function recovery, surgery was deferred in favor of stereotactic radiosurgery. LESSONS: In ruptured AVMs, DTI may initially create an incomplete picture and false assumptions about white matter tract integrity. DTI should be repeated if delayed treatment is appropriate to ensure informed decision-making and prevent avoidable permanent neurological deficits. https://thejns.org/doi/10.3171/CASE24225.

Optimizing oocyte yield utilizing a machine learning model for dose and trigger decisions, a multi-center, prospective study.

The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022-April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = -174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.

Turn off that night light! Light-at-night as a stressor for adolescents.

Light-at-night is known to produce a wide variety of behavioral outcomes including promoting anxiety, depression, hyperactivity, abnormal sociability, and learning and memory deficits. Unfortunately, we all live in a 24-h society where people are exposed to light-at-night or light pollution through night-shift work - the need for all-hours emergency services - as well as building and street-lights, making light-at-night exposure practically unavoidable. Additionally, the increase in screentime (tvs and smart devices) during the night also contributes to poorer sleep and behavioral impairments. Compounding these factors is the fact that adolescents tend to be "night owls" and prefer an evening chronotype compared to younger children and adults, so these teenagers will have a higher likelihood of being exposed to light-at-night. Making matters worse is the prevalence of high-school start times of 8 am or earlier - a combination of too early school start times, light exposure during the night, and preference for evening chronotypes is a recipe for reduced and poorer sleep, which can contribute to increased susceptibility for behavioral issues for this population. As such, this mini-review will show, using both human and rodent model studies, how light-at-night affects behavioral outcomes and stress responses, connecting photic signaling and the circadian timing system to the hypothalamic-pituitary adrenal axis. Additionally, this review will also demonstrate that adolescents are more likely to exhibit abnormal behavior in response to light-at-night due to changes in development and hormone regulation during this time period, as well as discuss potential interventions that can help mitigate these negative effects.

Age-associated contraction of tumor-specific T cells impairs antitumor immunity.

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.