Faculty Bibliography

PURPOSE/UNASSIGNED:To evaluate whether a non-invasive approach to treat keratoconus with corneal cross-linking (CXL) using oral riboflavin and natural sunlight could represent a cost-effective alternative. METHODS/UNASSIGNED:In a prospective, controlled study, 16 male New Zealand White rabbits (32 eyes) underwent a two-step protocol. Step 1 quantified stromal riboflavin in 4 rabbits (8 eyes) after 14 days of oral riboflavin (6 mg/kg/day). Step 2 randomized the remaining 12 rabbits (24 eyes) 1:1 to oral riboflavin plus natural sunlight or sunlight alone. After a 2,700 klux·h cumulative sunlight dose, corneal biomechanics were assessed by optical coherence tomography elastography and uniaxial stress-strain extensometry. RESULTS/UNASSIGNED:= .039), consistent with reduced apparent stiffness. CONCLUSIONS/UNASSIGNED:Oral riboflavin combined with ambient sunlight did not induce corneal stiffening under the tested conditions. Stromal riboflavin levels were nearly 500-fold lower than those achieved with standard CXL, indicating the tested approach is unlikely to serve as an effective standalone cross-linking strategy. The observed posterior corneal stiffness reduction may reflect ultraviolet-A-induced stromal degradation or subthreshold photochemical effects rather than true cross-linking.

OBJECTIVES/OBJECTIVE:To systematically evaluate the certainty of evidence for treatment strategies across age groups and mood phases in bipolar disorder, and develop an open access web platform to facilitate shared decision making. DESIGN/METHODS:Living umbrella review, evaluation, analysis, and communication hub (U-REACH) project. DATA SOURCES/METHODS:PubMed, PsycInfo, and Cochrane library databases, from inception to 19 November 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/METHODS:Systematic reviews with network or pairwise meta-analyses of randomised controlled trials of pharmacological, nutraceutical, psychosocial, brain stimulation, or circadian rhythm based treatments, administered as monotherapy (without concurrent interventions), augmentation treatment (interventions added to an ongoing treatment regimen), or combination treatment (simultaneous initiation of two different interventions), examining any age group, bipolar disorder phase (ie, acute bipolar depression, mania or mixed episodes, or maintenance), treatment, control, or outcome. RESULTS:77 studies met the inclusion criteria (21 network meta-analyses and 56 pairwise meta-analyses), including 116 unique pharmacological (n=74), brain stimulation (n=18), nutraceutical (n=13), psychosocial (n=8), and circadian rhythm based (n=3) treatments as monotherapy, augmentation, or combination therapy, along with five control interventions. These studies covered 133 unique outcomes (45 efficacy outcomes and 88 safety outcomes) resulting in 2510 meta-analyses with Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) ratings of the certainty of the evidence as high (n=236), moderate (n=827), low (n=986), and very low (n=461). A communication hub, the Evidence Based Interventions for Bipolar Disorder (EBI-BD) platform, was developed and the full results are freely available (https://ebibd-database.org), including the preference based tool (12 interventions and 17 safety outcomes). Interventions effective across outcomes varied by phases. For bipolar depression, effective interventions in adults were cariprazine, divalproex or valproate, fluoxetine, ketamine (augmentation), lamotrigine, lumateperone, lurasidone, olanzapine, olanzapine with fluoxetine, and quetiapine, whereas effective interventions in children and adolescents were lurasidone and olanzapine with fluoxetine. For mania episodes, effective interventions in adults were aripiprazole, asenapine, carbamazepine, cariprazine, divalproex or valproate, haloperidol, lithium, olanzapine, paliperidone, quetiapine (also augmentation), risperidone (also as augmentation), tamoxifen, and ziprasidone, whereas effective interventions in children and adolescents were aripiprazole, asenapine, olanzapine, quetiapine, and risperidone. For maintenance, interventions effective across outcomes in adults were aripiprazole (also the long acting injectable formulation), asenapine, divalproex or valproate, lithium, olanzapine, group psychoeducation (augmentation), quetiapine, and risperidone long acting injectable formulation. Interventions effective across phases were aripiprazole (also as augmentation and as a long acting injectable formulation), asenapine, cariprazine, cognitive behavioural therapy (augmentation), divalproex or valproate, lamotrigine, lithium, olanzapine (also as augmentation), paliperidone, quetiapine (also as augmentation), and risperidone (also as augmentation and the long acting injectable formulation) (adults). Treatment effects by neuroscience based nomenclature classes are also reported. CONCLUSIONS:The EBI-BD tool can help clinicians make evidence based, personalised treatment decisions for bipolar disorder. This resource can inform clinical guidelines and provides a foundation for continuously improving bipolar disorder care as new evidence emerges. TRIAL REGISTRATION/BACKGROUND:Open Science Framework https://osf.io/pjmvn/ READERS' NOTE: This is a living systematic review and may be updated in the next two years if additional evidence emerges.

Stem diameter distributions underpin forest planning and inventory practice worldwide, yet permanent sample plot inventories are routinely truncated by merchantability limits and diameter caps. Truncated densities are the standard remedy, but those forms are seldom documented or supported in common software, so practitioners default to biased complete-form fits. We introduce a two-stage weighted least-squares workflow that retains the familiar complete-form implementation while recovering truncated-fit accuracy. Stage one estimates a scaling factor alongside the density parameters; stage two freezes that normaliser to deliver unbiased shape and scale estimates. Applied to fixed-area plots from Québec, Canada, the two-stage estimator tracks truncated Weibull and gamma fits across 32 species-group/cover-type combinations (root-mean-square error between one-stage truncated and two-stage complete fits:

Early life is characterized by heightened susceptibility to respiratory pathogens, yet the immune mechanisms that predispose infants to infection remain poorly defined. Using an infant mouse model of Streptococcus pneumoniae (Spn) colonization, we identify an age-dependent delay in IL-17 A production that was associated with prolonged bacterial colonization in infant mice. Consistent with a critical role for this pathway, IL-17 receptor A (IL-17RA)-deficient infant mice exhibited persistent Spn colonization of the upper respiratory tract (URT). Transcriptomic profiling of the URT from Spn-colonized IL-17RA-deficient infant mice revealed an enrichment of antiviral responses compared to WT controls and included increased expression of the interferon-stimulated gene Cxcl10, a chemokine whose expression is positively associated with Spn carriage in humans. These results suggested that IL-17RA signaling constrains the interferon response during URT Spn colonization. WT infant mice exhibited progressively increased expression of Cxcl10 during Spn colonization and was dependent on type 1 interferon (IFNAR1) signaling and the pore forming bacterial toxin, pneumolysin. Genetic deletion of Ifnar1 or Cxcl10, including myeloid cell-specific deletion of Ifnar1, accelerated bacterial clearance in infant mice. In contrast, adult mice exhibited earlier induction of IL-17 A, minimal induction of Cxcl10 expression, and no alteration in bacterial clearance rates following Ifnar1 or Cxcl10 deficiency. Taken together, our results reveal a developmental window in which delayed IL-17 A production postpones the IL-17RA-dependent restraint of the type I interferon/CXCL10 axis, thereby prolonging pneumococcal carriage through impaired myeloid cell-mediated bacterial clearance.

OBJECTIVES/OBJECTIVE:Propofol is used sparingly in pediatrics owing to the risk of propofol-related infusion syndrome (PRIS). The objective of this study is to evaluate the safety of propofol in pediatrics and describe its effectiveness at facilitating extubation and decreasing concomitant sedation. METHODS:This retrospective, descriptive study evaluated critically ill children who received continuous propofol infusions for at least 12 consecutive hours while admitted to pediatric, congenital cardiac, or neonatal intensive care units. The primary outcome was PRIS incidence. Secondary outcomes included change from baseline in laboratory parameters, discontinuation due to adverse effects, change in sedative requirements following sedation washout, and successful extubation. RESULTS:From January 1, 2019, to November 1, 2023, a total of 100 children received 120 courses of propofol infusions. The median infusion rate was 106 mcg/kg/min (IQR, 68-149) and 27.5% of courses exceeded 48 hours in duration. No PRIS events were identified. Patients experienced a moderate, non-duration-dependent increase in triglycerides, with no impact on aspartate aminotransferase (AST)/alanine aminotransferase (ALT) concentrations; 11.7% of infusions were discontinued for adverse effects. No children self-extubated while on propofol when used for peri-extubation (N = 49). Opioid and benzodiazepine requirements were decreased by 17% and 26% from baseline, respectively, during a 24-hour period following sedation washout (N = 26). CONCLUSIONS:Propofol was tolerated by most patients at doses commonly exceeding guideline-recommended maximum rate and duration. Propofol was safely used to facilitate extubation and decreased baseline sedative exposure when used for sedation washout in a complex critically ill pediatric population.

BackgroundX-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate DNM2 expression in adolescents and adults with XLMTM or ADCNM.MethodsScreening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle.ResultsTwenty-six patients were screened (15 DNM2, 11 MTM1); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in DNM2 and female MTM1 patients but consistently reduced in males with MTM1 (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs.ConclusionThis dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium falciparum, reside within a specialized compartment known as the parasitophorous vacuole (PV) during their intracellular life cycle. The PV membrane (PVM), which derives from the host plasma membrane upon invasion, serves as a selective barrier that permits nutrient acquisition while shielding the parasite from host defense mechanisms. Although the protein composition of the PVM has been studied extensively, its lipid organization remains poorly understood. Using the quick-freeze, freeze-fracture replica labeling (QF-FRL) method, we quantitatively analyzed the transbilayer distribution of phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and GM3 ganglioside in the PVM of T. gondii and P. falciparum. Unlike host cell plasma membranes, where these lipids exhibit strict asymmetry-PtdSer and PtdEtn confined to the cytoplasmic leaflet and GM3 to the exoplasmic leaflet-we found that all three lipids were symmetrically distributed across both leaflets of the PVM. This striking loss of lipid asymmetry suggests that the PVM undergoes profound remodeling during infection. The presence of PtdSer and PtdEtn in the luminal leaflet may facilitate the binding of perforin-like proteins (PLP1s) during egress. These findings reveal a unique feature of the PVM that redefines our understanding of host-parasite membrane biology.

This study examined some physical and techno-functional properties of locust (Locusta migratoria) powder produced by infrared drying at temperatures of 60, 70, and 80 °C. Water activity, pH, Carr's index, Hausner ratio, water holding capacity (WHC), oil holding capacity (OHC), and color parameters of the powders were measured. In addition, infrared drying kinetics were analyzed. Increasing the drying temperature from 60 to 80 °C resulted in a 2.8-fold reduction in drying time, without causing significant changes in the measured properties. Except for WHC, the properties of infrared-dried powders were comparable to those of freeze-dried powder. WHC (2.1-2.3 g water/g) of infrared-dried powders was lower than that of the freeze-dried powder (3.3 g water/g). The locust powder exhibited poor flowability. Drying occurred in the falling rate period, with the Page model best describing the drying behavior. Effective moisture diffusivity (D _eff) ranged from 1.17 × 10^-10 to 10.9 × 10^-7 m²/s, and the activation energy was calculated as 53.81 kJ/mol. The influence of drying temperature on the drying rate was most pronounced during the early stages of drying. Overall, infrared drying, with its shorter processing time, appears to be a promising alternative for the production of locust powder.

INTRODUCTION/UNASSIGNED:"Positive" outcomes such as flourishing and personal recovery are important predictors of physical health, mental illness, quality of life, and all-cause mortality. However, behavioral health outcome measures often emphasize symptom reduction, while overlooking "positive" outcomes. The objective of this study is to describe (1) the outcomes most important to individuals with major depressive disorder (MDD) and (2) "positive" outcomes and psychiatric symptoms in a real-world sample of young adults with MDD. MATERIALS AND METHODS/UNASSIGNED:Forty-three participants aged 18-35 with a diagnosis of MDD receiving outpatient behavioral health treatment in an urban safety-net psychiatry department completed online surveys identifying factors most important to recovery and standardized measures of flourishing, personal recovery, functioning, and symptoms of depression and anxiety. RESULTS/UNASSIGNED:Most participants (61.9%) had high symptoms of depression (Patient Health Questionnaire-8 (PHQ-8) ≥ 10), 16.7% were flourishing (Flourishing Scale ≥ 48), and 41.9% had high personal recovery (Brief INSPIRE-O ≥ 50). Factors ranked as "most important" for personal recovery included coping well with stressful events (39.5%), functioning well (34.9%), and having hopes and dreams for the future (30.2%). Notably, among individuals with low depressive symptoms, 60.0% reported low flourishing and 31.3% reported low personal recovery. CONCLUSIONS/UNASSIGNED:Individuals with MDD value a diverse range of outcomes, and exhibit a large variation in levels of depressive symptoms and characteristics of "positive" mental health. Aligning outcome tracking with patient-defined goals may provide a more comprehensive understanding of overall mental health.