Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

4-Amidophenol Quinone Methide Precursors: Effective and Broad-Scope Nonoxime Reactivators of Organophosphorus-Inhibited Cholinesterases and Resurrectors of Organophosphorus-Aged Acetylcholinesterase.

Acetylcholinesterase (AChE) inhibition by organophosphorus (OP) compounds poses a serious health risk to humans. While many therapeutics have been tested for treatment after OP exposure, there is still a need for efficient reactivation against all kinds of OP compounds, and current oxime therapeutics have poor blood-brain barrier penetration into the central nervous system, while offering no recovery in activity from the OP-aged forms of AChE. Herein, we report a novel library of 4-amidophenol quinone methide precursors (QMP) that provide effective reactivation against multiple OP-inhibited forms of AChE in addition to resurrecting the aged form of AChE after exposure to a pesticide or some phosphoramidates. Furthermore, these QMP compounds also reactivate OP-inhibited butyrylcholinesterase (BChE) which is an in vivo, endogenous scavenger of OP compounds. The in vitro efficacies of these QMP compounds were tested for reactivation and resurrection of soluble forms of human AChE and BChE and for reactivation of cholinesterases within human blood as well as blood and brain samples from a humanized mouse model. We identify compound 10c as a lead candidate due to its broad-scope efficacy against multiple OP compounds as well as both cholinesterases. With methylphosphonates, compound 10c (250 µM, 1 h) shows >60% recovered activity from OEt-inhibited AChE in human blood as well as mouse blood and brain, thus highlighting its potential for future in vivo analysis. For 10c, the effective concentration (EC50) is less than 25 µM for reactivation of three different methylphosphonate-inhibited forms of AChE, with a maximum reactivation yield above 80%. Similarly, for OP-inhibited BChE, 10c has EC50 values that are less than 150 µM for two different methylphosphonate compounds. Furthermore, an in vitro kinetic analysis show that 10c has a 2.2- and 92.1-fold superior reactivation efficiency against OEt-inhibited and OiBu-inhibited AChE, respectively, when compared to an oxime control. In addition to 10c being a potent reactivator of AChE and BChE, we also show that 10c is capable of resurrecting (ethyl paraoxon)-aged AChE, which is another current limitation of oximes.

Exertional Heatstroke Survivors' Knowledge and Beliefs about Exertional Heatstroke Diagnosis, Treatment, and Return to Play.

CONTEXT: Little information exists regarding what exertional heatstroke (EHS) survivors know and believe about EHS best practices. Understanding this would help clinicians focus educational efforts to ensure survival and safe return-to-play following EHS. OBJECTIVE: We sought to better understand what EHS survivors knew about EHS seriousness (e.g., lethality, short- and long-term effects), diagnosis and treatment procedures, and recovery. Design: Multi-year, cross-sectional, descriptive design. SETTING: An 11.3-km road race located in the Northeastern United States in August 2022 and 2023. PATIENTS OR OTHER PARTICIPANTS: Forty-two of 62 runners with EHS (15 women, 27 men; age: 33±15 y; pre-treatment rectal temperature [TREC]: 41.5±0.9°C). INTERVENTIONS: Medical professionals evaluated runners requiring medical attention at the finish line. If they observed TREC ≥40°C with concomitant central nervous system dysfunction (CNS) EHS was diagnosed and patients were immersed in a 189.3-L tub filled with ice-water. Before medical discharge, we asked EHS survivors 15 questions about their experience and knowledge of select EHS best practices. Survey items were piloted and validated by experts and laypersons a priori (content validity index ≥0.88 for items and scale). MAIN OUTCOME MEASURES: Survey responses. RESULTS: Sixty-seven percent (28/42) of patients identified EHS as potentially fatal and 76% (32/42) indicated it negatively affected health. Seventy-nine percent (33/42) correctly identified TREC as the best temperature site to diagnose EHS. Most patients (74%, 31/42) anticipated returning to normal exercise within 1 week post-EHS; 69% (29/42) stated EHS would not impact future race participation. Patients (69%, 29/42) indicated it was important to tell their primary care physician about their EHS. CONCLUSIONS: Our patients were knowledgeable on the potential seriousness and adverse health effects of EHS and the necessity of TREC for diagnosis. However, educational efforts should be directed towards helping patients understand safe recovery and return-to-play timelines following EHS.

Impact of Plant Protein Intakes on Nutrient Adequacy in the US.

There is an increasing interest in plant-based diets and higher levels of plant proteins due to rising concerns around health and environmental sustainability issues. We determined the effects of increasing quartiles of plant protein in the diet on nutrient adequacy using a large nationally representative observational dataset. Twenty-four-hour dietary-recall data from NHANES 2013-2018 from 19,493 participants aged 9+ years were used to assess nutrient intakes. Nutritional adequacy was assessed by estimating the percentage of the population with intakes below the EAR or above the AI. A quartile trend was assessed using regression and the significance was set at Pquartile trend < 0.05. With increasing quartiles of plant protein, the adequacy decreased for calcium, potassium, and vitamin D and increased for copper and magnesium for adolescents. Among the adults aged 19-50 years, the adequacy decreased for protein, choline, selenium, vitamin B12, and zinc and increased for copper, folate, iron, magnesium, thiamin, and vitamin C with increasing quartiles of plant protein. The adequacy for calcium, vitamin A, and zinc decreased and it increased for copper, folate, magnesium, thiamin, and vitamin C with increasing quartiles of plant protein among adults aged 51+ years. The results indicate that diets of mixed protein sources (from both animals and plants) are the most nutritionally adequate.

Dynamic reinforcement learning reveals time-dependent shifts in strategy during reward learning.

Different brain systems have been hypothesized to subserve multiple "experts" that compete to generate behavior. In reinforcement learning, two general processes, one model-free (MF) and one model-based (MB), are often modeled as a mixture of agents (MoA) and hypothesized to capture differences between automaticity vs. deliberation. However, shifts in strategy cannot be captured by a static MoA. To investigate such dynamics, we present the mixture-of-agents hidden Markov model (MoA-HMM), which simultaneously learns inferred action values from a set of agents and the temporal dynamics of underlying "hidden" states that capture shifts in agent contributions over time. Applying this model to a multi-step,reward-guided task in rats reveals a progression of within-session strategies: a shift from initial MB exploration to MB exploitation, and finally to reduced engagement. The inferred states predict changes in both response time and OFC neural encoding during the task, suggesting that these states are capturing real shifts in dynamics.

Body Bag Cooling with Two Different Water Temperatures for the Treatment of Hyperthermia.

INTRODUCTION: Exertional heatstroke (EHS) is a life-threatening condition that requires quick recognition and cooling for survival. Experts recommend using cooling modalities that reduce rectal temperature (TREC) faster than 0.16°C/min though rates above 0.08°C/min are considered "acceptable." Hyperthermic individuals treated in body bags filled with ice water (∼3°C) have excellent cooling rates (0.28 ± 0.09°C/min). However, clinicians may not have access to large amounts of ice or ice water when treating EHS victims. The purpose of this study was to determine if using a body bag filled with water near the upper limits of expert recommendations for EHS treatment would produce acceptable (>0.08°C/min) or "ideal (>0.16°C/min)" TREC cooling rates or different nadir values.METHODS: A total of 12 individuals (9 men, 3 women; age: 21 ± 2 yr; mass: 74.6 ± 10.2 kg; height: 179.5 ± 9.6 cm) exercised in the heat until TREC was 39.5°C. They lay supine while 211.4 ± 19.5 L of 10°C (Ten) or 15°C (Fifteen) water was poured into a body bag. Subjects cooled until TREC was 38°C. They exited the body bag and rested in the heat for 10 min.RESULTS: Subjects exercised in similar conditions and for similar durations (Ten = 46.3 ± 8.6 min, Fifteen = 46.2 ± 7.8 min). TREC cooling rates were faster in Ten than Fifteen (Ten = 0.18 ± 0.07°C/min, Fifteen = 0.14 ± 0.09°C/min). TREC nadir was slightly higher in Fifteen (37.3 ± 0.2°C) than Ten (37.1 ± 0.3°C).DISCUSSION: Body bag cooling rates met expert definitions of acceptable (Fifteen) and ideal (Ten) for EHS treatment. This information is valuable for clinicians who do not have access to or the resources for ice water cooling to treat EHS.Miller KC, Amaria NY. Body bag cooling with two different water temperatures for the treatment of hyperthermia. Aerosp Med Hum Perform. 2024; 95(4):194-199.

Network Polymer Properties Engineered Through Polymer Backbone Dispersity and Structure.

Dispersity (Ð or Mw/Mn) is an important parameter in material design and as such can significantly impact the properties of polymers. Here, polymer networks with independent control over the molecular weight and dispersity of the linear chains that form the material are developed. Using a RAFT polymerization approach, a library of polymers with dispersity ranging from 1.2-1.9 for backbone chain-length (DP) 100, and 1.4-3.1 for backbone chain-length 200 were developed and transformed to networks through post-polymerization crosslinking to form disulfide linkers. The tensile, swelling, and adhesive properties were explored, finding that both at DP 100 and DP 200 the swelling ratio, tensile strength, and extensibility were superior at intermediate dispersity (1.3-1.5 for DP 100 and 1.6-2.1 for DP 200) compared to materials with either substantially higher or lower dispersity. Furthermore, adhesive properties for materials with chains of intermediate dispersity at DP 200 revealed enhanced performance compared to the very low or high dispersity chains.

Biometry challenges in the longest eyes we have encountered to date.

Purpose: This report aims to present biometry challenges and solutions for a patient with the longest eyes we have encountered to date. Observations: A 41-year-old woman with a history of Crouzon syndrome, extreme axial myopia, and posterior segment staphylomas was referred for cataract evaluation. Optical biometry was attempted using two partial coherence interferometry and optical low-coherence reflectometry devices that were available in 2011. Neither device could measure the axial length (AL) of either eye, unfortunately. We were able to measure them by A scan ultrasound, however, with results of 40.59 mm for the right eye and 38.29 mm for the left eye. Shortly thereafter, she underwent uncomplicated phacoemulsification with posterior chamber intraocular lens implantation under topical anesthesia. Twelve years later, she returned for repeat optical biometry with 3 newer generation devices, 2 of which utilized swept-source optical coherence tomography (SS-OCT). Only 1 SS-OCT device, the Argos biometer, was able to obtain AL measurements, and they were 40.54 mm and 40.84 mm for the right and left eyes, respectively. Conclusions and importance: Biometry measurement using optical biometers on a patient with ALs greater than 40 mm was impossible in 2011 because of the relatively short gate for acceptable readings. Ultrasound biometry can also be challenging due to the presence of posterior staphylomas. However, a newer SS-OCT with a longer AL measurement capability enabled readings to be obtained more recently.

Does Prophylactic Stretching Reduce the Occurrence of Exercise-Associated Muscle Cramping? A Critically Appraised Topic.

CLINICAL SCENARIO: Exercise-associated muscle cramps (EAMC) are sudden, painful, and involuntary contractions of skeletal muscles during or after physical activity. The best treatment for EAMC is gentle static stretching until abatement. Stretching is theorized to relieve EAMC by normalizing alpha motor neuron control, specifically by increasing Golgi tendon organ activity, and physically separating contractile proteins. However, it is unclear if stretching or flexibility training prevents EAMC via the same mechanisms. Despite this, many clinicians believe prophylactic stretching prevents EAMC occurrence. CLINICAL QUESTION: Do athletes who experience EAMC during athletic activities perform less prophylactic stretching or flexibility training than athletes who do not develop EAMC during competitions? SUMMARY OF KEY FINDINGS: In 3 cohort studies and 1 case-control study, greater preevent muscle flexibility, stretching, or flexibility training (ie, duration, frequency) was not predictive of who developed EAMC during competition. In one study, athletes who developed EAMC actually stretched more often and 9 times longer (9.8 [23.8] min/wk) than noncrampers (1.1 [2.5] min/wk). CLINICAL BOTTOM LINE: There is minimal evidence that the frequency or duration of prophylactic stretching or flexibility training predicts which athletes developed EAMC during competition. To more effectively prevent EAMC, clinicians should identify athletes' unique intrinsic and extrinsic risk factors and target those risk factors with interventions. STRENGTH OF RECOMMENDATION: Minimal evidence from 3 prospective cohort studies and 1 case-control study (mostly level 3 studies) that suggests prophylactic stretching or flexibility training can predict which athletes develop EAMC during athletic competitions.

Computational and systems neuroscience: The next 20 years.

Over the past 20 years, neuroscience has been propelled forward by theory-driven experimentation. We consider the future outlook for the field in the age of big neural data and powerful artificial intelligence models.

Perspective: A Research Roadmap about Ultra-Processed Foods and Human Health for the United States Food System: Proceedings from an Interdisciplinary, Multi-Stakeholder Workshop.

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.

ASCRS clinical advisory on intracameral moxifloxacin injection for infection prophylaxis.

Moxifloxacin solution is frequently injected at the conclusion of cataract surgery for endophthalmitis prophylaxis. 2 different concentrations are most commonly available in the United States for intracameral (IC) use: 0.5% (5 mg/mL) and 0.1% (1 mg/mL). The recommended volume to be injected is different for the 2 concentrations, and incorrect dosing can increase the risk of toxic anterior segment syndrome or endophthalmitis. In addition, the U.S. Food and Drug Administration recently published an alert regarding potential adverse events associated with intraocular compounded moxifloxacin. This clinical advisory reviews the optimal dosing of IC moxifloxacin based on current evidence.

What Role Might There Be for Continuous Glucose Monitoring in the Assessment of Diabetes Risk?

The term "prediabetes" has traditionally been used to describe the state of abnormal glucose homeostasis (dysglycemia) that could eventually lead to developing clinical type 2 diabetes. The HbA1c, oral glucose tolerance testing, and fasting glucose measurements represent the standard approaches for assessing risk. However, they do not predict with complete accuracy, nor do they provide individualized risk assessment to determine who will develop diabetes. Use of continuous glucose monitoring (CGM) provides a more complete picture of inter- and intraday glucose excursions that may help clinicians and patients quickly identify dysglycemia and make informed personalized intervention decisions. This article discusses the utility of CGM as a tool for both risk assessment and risk management.

Impact of second primary malignancy post-autologous transplantation on outcomes of multiple myeloma: a CIBMTR analysis.

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P < .001 and HR 5.01, P < .001, respectively) and OS (HR 3.85, P < .001 and HR 8.13, P < .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.

Replay and compositional computation.

Replay in the brain has been viewed as rehearsal or, more recently, as sampling from a transition model. Here, we propose a new hypothesis: that replay is able to implement a form of compositional computation where entities are assembled into relationally bound structures to derive qualitatively new knowledge. This idea builds on recent advances in neuroscience, which indicate that the hippocampus flexibly binds objects to generalizable roles and that replay strings these role-bound objects into compound statements. We suggest experiments to test our hypothesis, and we end by noting the implications for AI systems which lack the human ability to radically generalize past experience to solve new problems.

Outcomes of Patients with Thrombocytopenia Evaluated at Hematology Subspecialty Clinics.

BACKGROUND: Thrombocytopenia is a frequently encountered laboratory abnormality and a common reason for hematology referrals. Workup for thrombocytopenia is not standardized and frequently does not follow an evidence-based algorithm. We conducted a systematic analysis to evaluate the laboratory testing and outcomes of patients evaluated for thrombocytopenia at hematology clinics in a tertiary referral center between 2013 and 2016. PATIENT AND METHODS: We performed a comprehensive chart review for patients evaluated for thrombocytopenia during the study period. Patients were followed for 1 year from the initial hematology evaluation and assessed for the development of a hematologic malignancy, rheumatologic, or infectious diseases among other clinical outcomes. RESULTS: We evaluated 472 patients with a median (range) age of 61 (17-94) years. The majority (63.8%) had mild thrombocytopenia. Within 1 year of follow-up, 14 patients (3.0%) were diagnosed with a hematologic malignancy. A higher likelihood of developing a hematologic malignancy was noted in patients with concurrent leukopenia (hazard ratio [HR] 9.97, 95% confidence interval [CI] 3.28-30.32, p < .01) and increasing age (HR per 10-year deciles 1.52, 95% CI 1.03-2.25, p = .03). In patients with asymptomatic isolated mild thrombocytopenia, laboratory testing did not reveal any significant positive findings and patients did not receive any new major diagnosis during the follow-up period. CONCLUSION: Our findings provide basis and call for development of an evidence-based algorithmic approach for evaluation of patients with thrombocytopenia, testing, and referrals. It also supports a conservative approach mainly driven by physical exam signs, symptoms, and other laboratory findings for patients with isolated mild thrombocytopenia.

Assessment of Boys' Responses to Interpersonal Conflict in Virtual Reality.

Background: Continuous advances in virtual reality (VR) technology have increased its potential for clinical use in the research, assessment, and treatment of mental health difficulties. One potential target for VR use is childhood behavior problems, which are often associated with social-cognitive deficits that can be difficult to measure or modify. Materials and Methods: We enrolled 36 boys between the ages of 8-13 to assess the usability of a VR device and its feasibility as a psychiatric tool for youth. Each participant experienced three virtual school cafeteria scenes that varied in antisocial content and the intentions of a virtual counterpart (VC) (control, ambiguous, or hostile). Following each scene, participants completed questions about ease and comfort in using the headset as well as an assessment of hostile attribution bias (HAB). HAB is the tendency to attribute hostile motivations to others' behaviors, which contributes to antisocial thoughts and behaviors. Following this VR use, participants completed a standard text assessment of HAB. Results: In general, participants reported the VR headset to be enjoyable and easy to use, and scenes worked as intended, with VCs in the hostile scene rated the meanest. In addition, boys with more conduct problems reported that virtual characters were meaner to them, despite no difference in text vignette measures of HAB. Conclusion: This study provides preliminary evidence supporting the further development of VR programs to assess and treat childhood behavior problems.