Bryan College

Among patients receiving ongoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy who experience stroke or myocardial infarction (MI), evidence is limited on the systemic safety of continuing injections and whether treatment should be paused or modified. To evaluate whether, among patients receiving intravitreal anti-VEGF therapy who experience cardiovascular events (CVE), there exist associations between anti-VEGF treatments administered shortly before or after CVE (peri-CVE) and mortality or major functional outcomes, and to evaluate whether systemic outcomes differ by anti-VEGF agents. This was a retrospective cohort study of TriNetX network deidentified electronic health records (EHR) from 2005 to 2025. This study setting was a multicenter, EHR-based network analysis including individuals with stroke or MI with established anti-VEGF history (≥3 months pre-CVE), matched between those receiving 1 or more anti-VEGF injections within 14 days before or up to 6 weeks after CVE and those with no anti-VEGF from 3 months before to 3 months after. Propensity score matching (PSM) balanced demographics, comorbidities, procedures, systemic medications, laboratory values, and anti-VEGF agent history. Exposures included intravitreal anti-VEGF during the peri-CVE window vs no peri-CVE anti-VEGF. Sensitivity analyses restricted exposure to 14 days or fewer pre-CVE and compared aflibercept, bevacizumab, or ranibizumab with other agents. The primary outcomes were 3-month and 1-year all-cause mortality, poststroke neurologic deficits, and post-MI heart failure. Data were expressed in relative risks (RRs) with 95% CIs. A total of 6073 and 5381 individuals with stroke or MI, respectively, were included before PSM. After PSM (1526 pairs with stroke; exposure [received peristroke anti-VEGF], mean [SD] age, 72.1 [12.9] years; 822 female [53.9%]; control [did not receive peristroke anti-VEGF], 72.7 [13.3] years; 840 female [55.0%]; and 1523 pairs with MI, exposure [received peri-MI anti-VEGF], 71.4 [13.5] years; 809 male [53.1%]; control [did not receive peri-MI anti-VEGF], 71.5 [13.3] years; 798 male [52.4%]), peristroke anti-VEGF was associated with lower mortality at 3 months (RR, 0.39; 95% CI, 0.29-0.53) and 1 year (RR, 0.52; 95% CI, 0.43-0.63) and fewer neurologic deficits at 3 months (RR, 0.64; 95% CI, 0.46-0.89) but not 1 year (RR, 0.79; 95% CI, 0.62-1.01). Peri-MI exposure was associated with lower mortality at 3 months (RR, 0.34; 95% CI, 0.26-0.43) and 1 year (RR, 0.58; 95% CI, 0.49-0.68) and lower heart failure at 3 months (RR, 0.65; 95% CI, 0.46-0.93) but not 1 year (RR, 0.87; 95% CI, 0.68-1.11). Timing-restricted analyses showed similar mortality findings without differences in neurologic deficits or heart failure. In agent-specific comparisons, there were no differences across aflibercept, bevacizumab, or ranibizumab for any outcome. Results of this cohort study reveal that peri-CVE anti-VEGF was not associated with increased mortality or morbidity. Outcomes did not differ among commonly used agents, supporting the safety of continuing intravitreal anti-VEGF therapy without modification during the peri-CVE period.

Reciprocal innovation, a model of sustained, multidirectional exchange in which health strategies are adapted, revisited, and refined across contexts, offers a compelling framework to rethink how implementation science can support global health equity by enabling dynamic, multidirectional learning across different contexts. Drawing on the EXTRA-CVD trial, a nurse-led cardiovascular disease prevention intervention designed to extend the HIV treatment cascade in United States (U.S.) HIV clinics, which adapted strategies informed by implementation research in Kenya and the U.S. Veterans Affairs health system, this perspective examines how reciprocal innovation can begin to emerge within existing research structures, as well as where opportunities for deeper exchange remain limited. We identify four operational domains of reciprocal innovation: care delivery strategies, end-user engagement, research methodologies, and research leadership and partnership. Across these domains, we describe how cross-context learning shaped intervention adaptation and site-level implementation in EXTRA-CVD, as well as missed opportunities where more intentional feedback, shared leadership, and methodological exchange could have strengthened multidirectional learning. Taken together, this work highlights both the potential and the practical challenges of reciprocal innovation in implementation research, emphasizing its role in moving beyond unidirectional knowledge transfer toward iterative, context-responsive learning. By embedding structures for iterative feedback, equity-centered governance, and multidirectional learning systems within research and implementation systems, future global partnerships can foster more inclusive, responsive, and sustainable health interventions.

Depression affects over 300 million people worldwide and is a leading cause of disability. Current treatments have limited efficacy in achieving remission and require several weeks to months of therapy for lessening depressive symptoms. Reduced autophagy is commonly observed in the brain of individuals with major depressive disorder, impairing cellular homeostasis and synaptic plasticity, the processes vital for mood regulation. A recent study published in the journal Nature reported that a key driver for depression in a mouse model of acute and chronic stress is an impaired autophagy in the lateral habenula, a brain region known to regulate motivation, reward, and aversion. Notably, direct infusion of beclin-1 peptide into this region rapidly restored autophagy markers and reduced depressive symptoms, highlighting a fast-acting mechanism distinct from the way conventional antidepressants act. Such effects were attributed to reduced excitatory neurotransmitter receptors, which could ease neuronal hyperactivity without affecting inhibitory neurotransmission, demonstrating that the selective autophagic degradation of excitatory receptors in the lateral habenula can mediate antidepressant effects. However, several issues remain to be addressed, including the long-term efficacy and the feasibility of the approach for clinical translation. This review critically discusses the proficiency, limitations, and clinical translatability of the lateral habenula autophagy enhancement approach. The promise of other autophagy enhancers and the possibility of combinational therapy, where drugs or dietary supplements could enhance autophagy, diminish neuroinflammation, and regulate neurotransmitters, is also discussed.

Accurate assessment of cardiac preload remains a clinical challenge, particularly in heart failure patients where preload manipulation is impractical or contraindicated. Ejection fraction (EF), while widely used, reflects a combination of preload, contractility, and afterload, and may obscure the specific contribution of preload. Inspired by a preload recruitable stroke work (PRSW) model for heart function, a concise, three factor expression for ejection fraction (EF) can be obtained where EF is directly proportional to preload, directly proportional to contractility, and inversely proportional to afterload. The contractility and afterload factors are common metrics; whereas the preload factor, filling fraction (FF), is a novel, dimensionless preload metric that sets a physiologic upperbound on EF. Unfortunately, FF measurement requires an estimate of the volume intercept or dead-space volume of the left ventricle, and such a measure has, conventionally, required preload manipulation with extrapolation to the volume axis. To address this, we propose a single-beat extrapolation method for estimating the volume intercept using end-diastolic and end-systolic measurements. In-silico testing across 10,000 synthetic left ventricular geometries demonstrates strong agreement between the estimated intercept and actual, prescribed dead-space volumes. This method enables non-invasive computation of FF from single-beat data without the need for in vivo preload manipulation. Potential clinical applications include characterizing cardiac function, stratifying heart failure subtypes, and enhancing diagnostic precision when EF is preserved but preload reserve is impaired. Future validation in clinical imaging datasets is warranted to assess real-world applicability.

Background: Stroke induces acute intestinal epithelial dysfunction and increased gut permeability, contributing to systemic inflammation and neurotoxicity. We previously demonstrated that transplantation of intestinal epithelial stem cells (IESCs) from young donors mitigates both acute and chronic stroke deficits in aging animals. However, IESCs rarely engraft or differentiate in vivo, suggesting that their therapeutic efficacy is mediated largely by paracrine secretions. Here, we tested the hypothesis that IESC organoid–derived conditioned media (IESC-CM) are sufficient to confer neuroprotection by restoring gut barrier integrity and attenuating systemic inflammation, thereby improving acute and chronic stroke outcomes. Methods: IESCs isolated from young male or female rats were expanded as intestinal oganoids and conditioned media (IESC-CM) was collected. Middle-aged male and female rats were subjected to endothelin-1–induced middle cerebral artery occlusion (MCAo) and randomized to vehicle or IESC-CM treatment groups. IESC-CM was administered intraperitoneally at 4, 24, and 48 h post-stroke. Infarct volume and sensorimotor function were assessed at 4 d post-stroke. At 30 d, animals were tested for Social Interaction, Novel Object Recognition test, and Barnes maze . Circulating gut permeability markers and cytokines were quantified at acute and chronic phases. Results: IESC-CM significantly reduced infarct volume, improved sensorimotor recovery, and attenuated gut permeability in both sexes in the acute phase. In the chronic phase, vehicle-treated MCAo animals exhibited depressive-like behaviors and impaired cognition, whereas IESC-CM treatment normalized affective behaviors in both sexes. Strikingly, cognitive benefits were sex-dependent: IESC-CM improved episodic memory, spatial learning, and retrieval in males, but not in females. This sex-specific effect was paralleled by differential cytokine modulation, with IL-17A levels significantly reduced by IESC-CM in males but unchanged in females. Conclusion: These findings demonstrate that IESC-derived secretomes confer robust neuroprotection acutely in both sexes, but promote long-term cognitive recovery preferentially in males. The divergence may reflect sex differences in the composition of the IESC secretome, resulting in greater suppression of proinflammatory cytokines and and enhanced gut restoration in males as compared to females.

About half of medical residents report experiencing bullying behaviors in training settings, and these negative acts adversely impact the work environment in a variety of ways. Understanding perceptions of how often others report bullying behavior (descriptive norms) and how approving others are of these behaviors (injunctive norms) lays important groundwork for potential intervention studies in medical education. The primary aims of our study were to (a) examine the accuracy of descriptive and injunctive norms related to reporting bullying behaviors, and (b) determine whether individuals with larger self-other differences would be more likely to report bullying behaviors. We conducted exploratory analyses to examine associations between self-valuation (eg, self-compassion) and perceived risk of consequences of reporting bullying behavior. Our analyses also explored differences in perceptions of risk related to experiencing retaliation among women and those who identified as underrepresented in medicine. Data were gathered and analyzed as part of the 2024 Council of Academic Family Medicine Educational Research Alliance survey of family medicine educators and practicing physicians. Faculty and staff working in family medicine education (N = 1,096) tended to be inaccurate when estimating others' behaviors and beliefs about reporting behavior. Self-other differences predicted one's tendency to engage in reporting bullying behavior. Our study expanded on previous findings that suggested that those in medical education have inaccurate peer perceptions of attitudes and behaviors related to reporting bullying behavior. Further, our study provided additional support for studying the use of social norms interventions as a strategy to modify maladaptive perspectives and behaviors in this setting.

Postpartum depression (PPD) is a major public health problem with significant adverse consequences for maternal mental health and infant development. Despite this, there exists surprisingly little data concerning neurobiological underpinnings of PPD. The present study examined oxytocin (OT) and vasopressin (VP), two hormones critical for mood regulation and social/maternal behavior, to provide descriptive data regarding the role of the two hormones in PPD and intergenerational risk. Twelve postpartum mothers (5 with PPD and 7 without PPD) and their infants participated in the study. Following a baseline blood and saliva sample collection, mothers and infants engaged in a 15-min semi-structured play interaction. Blood samples were collected from mothers at 5, 10, 15, and 40min following the start of the interaction, and saliva samples were collected from mothers and infants at 20min following the start of the interaction. We documented trajectories of changes in OT and VP before, during, and after the interaction, as well as associations between mothers' and infants' OT and VP. We observed sample-wide increases in maternal OT at 5, 10, 15, and 20min, and decreases in maternal VP at 15min. Infant OT was increased at 20min. Mothers with PPD showed a more gradual increase in OT during the interaction compared to mothers without PPD. Following the interaction, OT decreased and reached its pre-interaction baseline level in mothers without PPD, but such return to baseline was not observed in mothers with PPD. Maternal and infant hormone levels generally showed positive associations. The positive association was more pronounced in OT than VP, and in the non-PPD than PPD group. OT and VP generally showed negative associations. Our data further illustrated potential inter-relationships among PPD, OT, and several important maternal characteristics. Our findings illustrate trajectories of the mother's and infant's OT and VP before, during, and after interactions, and alterations of these trajectories in the presence of PPD. The findings add valuable data to the field's understanding of how the OT and VP systems function in healthy postpartum mothers and infants and how they become dysregulated in the presence of PPD.

Purpose Disaster immunity capability has been demonstrated to benefit firms during supply chain disruptions. However, research on how supply chain digitalization provides data to assist firms in achieving immunity capability is lacking. Supply chain digitalization focuses on the application of digital technologies (e.g. the Internet of Things (IoT), artificial intelligence (AI) and blockchain) to optimize supply chain operations. This paper aims to answer the research question: How can supply chain digitalization contribute to organizational disaster immunity capability? Design/methodology/approach We propose a research model based on dynamic capabilities theory to address the research question by exploring relationships between supply chain digitalization, process integration, innovation speed and disaster immunity capabilities. Two empirical studies, a survey and a vignette-based experiment, provide empirical support using data collected from manufacturing and service companies to test the proposed model. Findings The results demonstrate that supply chain digitalization significantly enhances disaster immunity capability through the mediating effects of supply chain process integration and innovation speed. Originality/value This study contributes to existing literature by introducing supply chain process integration and innovation speed as mediating variables that explain how digitalization leads to disaster immunity capability. This paper provides practical, actionable insights for organizations to prepare for future disasters and make informed decisions.

Women affected by obstructive sleep apnea (OSA) face an increased risk of cognitive impairment and mood disorders, with emerging evidence suggesting that neuroinflammation plays a significant role in the pathophysiology. OSA causes intermittent hypoxia and activates the immune response in the brain. Additionally, menopause is a separate risk factor that can put women with OSA at an even higher risk of cognitive decline. Although neuroinflammation occurs in OSA, the underlying mechanisms of the neuroinflammatory response are not well understood, and it remains unknown whether ovarian hormones modify these mechanisms. To examine the impact of OSA and hormone status on neuroinflammation, we used a 7-day chronic intermittent hypoxia (CIH) and ovariectomy (OVX) to model OSA and hormone status in female rats, respectively. To examine neuroinflammation, we investigated changes in brain microglia and astrocyte morphology and the number of reactive cells. We used a comprehensive three-dimensional reconstruction and analysis of microglia and astrocytes to study the changes in the morphology of these cells. We focused on brain regions associated with cognitive function (CA1 of the dorsal hippocampus, medial prefrontal cortex – mPFC, caudate and putamen – CP). Specifically, immunofluorescence of Iba1 (microglia marker) and GFAP (astrocyte marker) was conducted, along with measuring indicators of glial reactivity (branching, complexity, cell size, and number of reactive cells). Our results found that there were CIH and hormone effects on neuroinflammation in these brain regions. Microglia activation was impacted by an interaction between CIH and hormone status in all regions examined. In contrast, astrocytes showed no reactivity in all regions examined, regardless of CIH or hormone status. These findings suggest that menopause and OSA may impact microglia remodeling in brain areas associated with cognitive function. Microglia-specific neuroinflammation may be part of early mechanisms that lead to the cognitive impairments observed in CIH and hormone loss in females.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a serious complication affecting roughly 24% of critically ill pediatric patients. Yet, data is limited regarding SA-AKI in pediatric type 1 diabetes mellitus (T1DM). This study’s aim was to provide pilot data for future prospective research on SA-AKI in children with or without T1DM. Subjects and Methods: Retrospective pilot study included 30 pediatric intensive care unit patients – one infant, 19 children (>1–12 years), and 10 adolescents (13–18 years). Consistent with the prevailing diagnostic criteria utilized at the time of admission (2015–2020), sepsis was defined according to the 2005 International Pediatric Sepsis Consensus Conference criteria, as Systemic Inflammatory Response Syndrome plus suspected or confirmed infection. Analyses were conducted in jamovi (v2.6.26). Results: Critically ill T1DM patients were statistically significantly more likely to experience SA-AKI ( P < 0.001). 84.61% of T1DM patients ( n = 13) developed SA-AKI, with higher mean glucose levels on admission across bacterial, viral, and culture-negative endotypes as compared to T1DM patients without SA-AKI. Vancomycin use associated with SA-AKI was not statistically significant, though all T1DM patients who received vancomycin ( n = 4) developed SA-AKI. There was no significant difference among blood urea nitrogen (BUN), creatinine (Cr), BUN to Cr ratios, and baseline to admission Cr ratios in T1DM versus non-T1DM children and adolescents. However, higher mean values were observed in T1DM children than in adolescents. Conclusions: Results may provide preliminary evidence that T1DM confers increased susceptibility to SA-AKI. Additional studies are needed to determine if such mechanisms exist and promote interventions to prevent SA-AKI in critically ill pediatric T1DM patients.