Can Multisensory Olfactory Training Improve Olfactory Dysfunction Caused by COVID-19?

Approximately 30-60% of people suffer from olfactory dysfunction (OD) such as hyposmia or anosmia after being diagnosed with COVID-19; 15-20% of these cases last beyond resolution of the acute phase. Previous studies have shown that olfactory training can be beneficial for patients affected by OD caused by viral infections of the upper respiratory tract. The aim of the study is to evaluate whether a multisensory olfactory training involving simultaneously tasting and seeing congruent stimuli is more effective than the classical olfactory training. We recruited 68 participants with persistent OD for two months or more after COVID-19 infection; they were divided into three groups. One group received olfactory training which involved smelling four odorants (strawberry, cheese, coffee, lemon; classical olfactory training). The other group received the same olfactory stimuli but presented retronasally (i.e., as droplets on their tongue); while simultaneous and congruent gustatory (i.e., sweet, salty, bitter, sour) and visual (corresponding images) stimuli were presented (multisensory olfactory training). The third group received odorless propylene glycol in four bottles (control group). Training was carried out twice daily for 12 weeks. We assessed olfactory function and olfactory specific quality of life before and after the intervention. Both intervention groups showed a similar significant improvement of olfactory function, although there was no difference in the assessment of quality of life. Both multisensory and classical training can be beneficial for OD following a viral infection; however, only the classical olfactory training paradigm leads to an improvement that was significantly stronger than the control group.

An overview of the CANVAS Program and CREDENCE trial: The primary outcomes and key clinical implications for those managing patients with type 2 diabetes.

AIMS: To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). METHODS AND RESULTS: The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. CONCLUSION: Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

Using Gaming to Promote Vaccination Among Youth: A Systematic Review.

Introduction: While vaccines are crucial for disease prevention, disparities in vaccination coverage persist among youths aged 10 to 29 years, including within the United States. Serious games are emerging as a new strategy to address vaccine hesitancy. This systematic review aimed to aggregate and assess the current evidence on game-based interventions to improve youth vaccination rates, evaluating their impact and identifying factors influencing their effectiveness. Methods: This systematic review was conducted through a meticulous search and evaluation of literature from databases including PubMed, Cumulative Index to Nursing and Allied Health Literature database, ProQuest platform, Cochrane Library, and Google Scholar. Studies were included if they (a) were designed with the purpose of improving youth vaccination rates; (b) were published in English; (c) were published between January 2011 and June 2023; and (d) evaluated the effect of game-based interventions. Search terms included Medical Subject Headings terms and keywords of the eligible articles. Results: Out of 269 studies, 11 were included in the final analysis of this review. The earliest study dated back to 2013, with 5 being randomized controlled trial and 6 studies incorporating theoretical models in their design or outcome measures. The findings indicated a generally positive effect of game-based interventions on vaccine-related knowledge. However, the impact on actual vaccine uptake was limited. In-game avatar customization and collaboration games were found as effective tools for player engagement. Conclusion: The review findings indicated that serious games boost vaccine knowledge but lack strong evidence for influencing youth vaccine uptake. More rigorous research and tailored game designs are needed to determine the effectiveness of game-based interventions and effectively address the diverse needs of youth in vaccine decision-making.

Strategic Use of Biodegradable Temporizing Matrix (BTM) in Wound Healing: A Case Series in Asian Patients.

Skin and soft tissue reconstruction has long been based on the reconstructive ladder. However, a skin substitute has become popular due to its predictable outcomes, without donor-site morbidity. The biodegradable temporizing matrix (BTM; NovoSorb, PolyNovo Ltd., Port Melbourne, Australia) is a synthetic skin substitute that has recently gained its clinical application. Compared with those of other dermal templates, the clinical efficacy and performance of the BTM are not well established, especially among the Asian population. This study aims to share our experience and strategy of using BTM in various wound conditions. The data of patients who underwent skin and soft tissue reconstruction with BTM at a single institution between January 2022 and December 2023 were reviewed. The patient demographics, wound characteristics, surgical details, secondary procedures, and complications were recorded and analyzed. Postoperative 6-month photographs were collected and independently evaluated by two plastic surgeons and two wound care center nurses using the Manchester Scar Scale (MSS). This study included 37 patients, consisting of 22 males and 15 females with a mean age of 51.8 years (range, 18-86 years old). The wound etiologies included trauma (67.6%), necrotizing soft tissue infection (16.2%), burns (10.8%), toe gangrene (2.7%), and scar excision (2.7%). The average wound area covered by BTM was 50.6 ± 47.6 cm2. Among the patients, eight received concomitant flap surgery and BTM implantation, 20 (54.1%) underwent subsequent split-thickness skin grafts (STSG), and 17 had small wounds (mean: 21.6 cm2) healed by secondary intention. Infection was the most common complication, affecting six patients (n = 6 [16.2%]), five of whom were treated conservatively, and only one required debridement. Thirty-three patients (89.2%) had good BTM take, and only four had BTM failure, requiring further reconstruction. At the last follow-up, 35 out of the 37 patients (94.6%) achieved successful wound closure, and the total MSS score was 10.44 ± 2.94, indicating a satisfactory scar condition. The patients who underwent BTM grafting without STSG had better scar scores than those who received STSG (8.71 ± 2.60 vs. 11.18 ± 2.84, p = 0.039). In conclusion, the BTM is effective and feasible in treating various wounds, with relatively low complication rates, and it can thus be considered as an alternative for skin and soft tissue reconstruction. When combined with adipofasical flap reconstruction, it achieves a more comprehensive anatomical restoration.

Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a Systemic Fluoropyrimidine.

PURPOSE: Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS: The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record-based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed loop reporting system for abnormal test results was created. Before implementation, targeted education was provided to providers, pharmacists, and nurses, and a failure mode and effects analysis was performed. Program rollout was staged over a 6-month period. RESULTS: At 10 months, the rate of preemptive testing increased from a baseline of 26% to a sustained rate of >90%. In the six network sites, the testing rate increased from 9% to 96%. A total of 1,043 patients have been tested preemptively; allelic variants have been identified in 43 (4.1%). Among 25 evaluable patients, dose reduction or change to a non-fluoropyrimidine-based regimen was accomplished in 96%. CONCLUSION: Preemptive DPYD testing is feasible, and high rates of testing can be achieved using an opt-out, reminder-based program. We provide the details of the implementation and encourage others to emulate it.

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Knowledge, attitudes, and behaviors related to dietary salt intake and the acceptability of salt substitute among the Australian culturally and linguistically diverse community: An online survey.

The Australian culturally and linguistically diverse (CALD) communities may be at higher risk of salt intake than recommended given the use of a combination of discretionary sources and exposure to processed foods within a western country. This survey aimed to understand the knowledge, attitudes, and behaviors toward dietary salt and the acceptability of salt substitutes in the CALD communities. An online cross-sectional survey was conducted among adults who self-reported being a part of a CALD community, which was defined as non-Indigenous cultural groups in Australia having cultural or linguistic connections with their overseas place of birth, ancestry or ethnic origin, religion, preferred language or language spoken at home. A total of 218 respondents opened the survey link. A total of 196 completed the entire survey. The majority of respondents (162, 83%) were aware that high salt intake causes serious health problems. Altogether 134 (69%) respondents were aware that there is a recommended amount for daily salt consumption although only 59 (44%) knew precise recommendations as <5 g salt per day. Around one quarter of the respondents rarely or never looked for ?low in salt'' or ?reduced salt'' messages on food labels when shopping. Over half specified they always or often added salt during cooking or preparing foods in the household. Almost 4 in 5 CALD respondents were willing to reduce their salt intake for health and 3 in 4 were open to trying a salt substitute. Further research into the utility of a salt substitute intervention in the Australian CALD community is warranted.

Refractive Error Change and Overminus Lens Therapy for Childhood Intermittent Exotropia.

Importance: Increased myopic shift was found to be associated with 1 year of overminus spectacle treatment for children with intermittent exotropia (IXT). Persistence of myopic shift after discontinuing overminus spectacles is unknown. Objective: To compare refractive error change over 3 years in children with IXT originally treated with overminus vs nonoverminus spectacles. Design, Setting, and Participants: This study was an 18-month extension of the Trial of Overminus Spectacle Therapy for Intermittent Exotropia cohort, which previously randomized children aged 3 to 10 years with IXT and baseline spherical equivalent refractive error (SER) between -6.00 diopters (D) and 1.00 D to overminus spectacles (-2.50 D for 12 months, -1.25 D for 3 months, and nonoverminus for 3 months) or nonoverminus spectacles. Children were recruited from 56 sites from July 2010 to February 2022. Data were analyzed from February 2022 to January 2024. Interventions: After trial completion at 18 months, participants were followed up at 24 and 36 months. Treatment was at investigator discretion from 18 to 36 months. Main Outcomes and Measures: Change in SER (cycloplegic retinoscopy) from baseline to 36 months. Results: Of 386 children in the Trial of Overminus Spectacle Therapy for Intermittent Exotropia, 223 (57.8%) consented to 18 months of additional follow-up, including 124 of 196 (63.3%) in the overminus treatment group and 99 of 190 (52.1%) in the nonoverminus treatment group. Of 205 children who completed 36-month follow-up, 116 (56.6%) were female, and the mean (SD) age at randomization was 6.2 (2.1) years. Mean (SD) SER change from baseline to 36 months was greater in the overminus group (-0.74 [1.00] D) compared with the nonoverminus group (-0.44 [0.85] D; adjusted difference, -0.36 D; 95% CI, -0.59 to -0.12; P = .003), with 30 of 112 (26.8%) in the overminus group having more than 1 D of myopic shift compared with 14 of 91 (15%) in the nonoverminus group (risk ratio, 1.8; 95% CI, 1.0-3.0). From 12 to 36 months, mean (SD) myopic shift was -0.34 (0.67) D and -0.36 (0.66) D in the overminus and nonoverminus groups, respectively (adjusted difference, -0.001 D; 95% CI, -0.18 to 0.18; P = .99). Conclusions and Relevance: The greater myopic shift observed after 1 year of -2.50-D overminus lens treatment remained at 3 years. Both groups had similar myopic shift during the 2-year period after treatment weaning and cessation. The risk of myopic shift should be discussed with parents when considering overminus lens treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02807350.

Identifying low acuity Emergency Department visits with a machine learning approach: The low acuity visit algorithms (LAVA).

OBJECTIVE: To improve the performance of International Classification of Disease (ICD) code rule-based algorithms for identifying low acuity Emergency Department (ED) visits by using machine learning methods and additional covariates. DATA SOURCES: We used secondary data on ED visits from the National Hospital Ambulatory Medical Survey (NHAMCS), from 2016 to 2020. STUDY DESIGN: We established baseline performance metrics with seven published algorithms consisting of International Classification of Disease, Tenth Revision codes used to identify low acuity ED visits. We then trained logistic regression, random forest, and gradient boosting (XGBoost) models to predict low acuity ED visits. Each model was trained on five different covariate sets of demographic and clinical data. Model performance was compared using a separate validation dataset. The primary performance metric was the probability that a visit identified by an algorithm as low acuity did not experience significant testing, treatment, or disposition (positive predictive value, PPV). Subgroup analyses assessed model performance across age, sex, and race/ethnicity. DATA COLLECTION: We used 2016-2019 NHAMCS data as the training set and 2020 NHAMCS data for validation. PRINCIPAL FINDINGS: The training and validation data consisted of 53,074 and 9542 observations, respectively. Among seven rule-based algorithms, the highest-performing had a PPV of 0.35 (95% CI [0.33, 0.36]). All model-based algorithms outperformed existing algorithms, with the least effective-random forest using only age and sex-improving PPV by 26% (up to 0.44; 95% CI [0.40, 0.48]). Logistic regression and XGBoost trained on all variables improved PPV by 83% (to 0.64; 95% CI [0.62, 0.66]). Multivariable models also demonstrated higher PPV across all three demographic subgroups. CONCLUSIONS: Machine learning models substantially outperform existing algorithms based on ICD codes in predicting low acuity ED visits. Variations in model performance across demographic groups highlight the need for further research to ensure their applicability and fairness across diverse populations.

Health Care Use Among Patients Retroactively Insured via a Hospital-Based Insurance Linkage Program.

OBJECTIVE: Over 25% of the 27 million uninsured individuals in the United States are eligible for Medicaid. Many hospitals have insurance linkage programs that assist eligible patients with enrollment, but little is known about the impact of these programs on care utilization. This research assessed health care utilization and health outcomes among patients enrolled in Medicaid via a hospital-based insurance linkage program. METHODS: This retrospective cohort study included adults aged 18-64 admitted to the hospital from 2016 to 2021. Those who obtained insurance retroactively via insurance linkage (RI) were compared with those who presented with Medicaid (MI) or remained uninsured (UI). The primary outcome was the presence of at least one visit with a primary care provider (PCP) in the 12 months following index admission. Secondary outcomes included having an assigned PCP, ED revisits, and hospital readmissions. For patients with diabetes and hypertension, 12-month hemoglobin A1c (HbA1c) and blood pressure (BP) readings were tracked. RESULTS: Of 3882 patients admitted with no insurance, 2905 (74.8%) were enrolled in insurance (RI). In multivariable analysis, RI patients were 14% more likely (OR 1.14, p = 0.020) to have completed at least one PCP visit by 12 months after index admission compared to those with preexisting Medicaid (MI), and uninsured patients were 29% less likely (OR 0.71, p = 0.003). MI and RI patients also had more ED revisits (p < 0.001) and greater 12-month reductions in blood pressure (p < 0.001) compared with uninsured patients. CONCLUSION: Hospital-based insurance linkage reached three-quarters of uninsured patients and was associated with increased utilization of acute and outpatient health care services. An acute care encounter represents an opportunity to connect patients to insurance, a key step toward improving their health outcomes.

Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells.

Mutations in the solute linked carrier family 4 member 11 (SLC4A11) gene are associated with congenital hereditary endothelial dystrophy (CHED) and Fuchs corneal endothelial dystrophy type 4 (FECD4), both characterized by corneal endothelial cell (CEnC) dysfunction and/or cell loss leading to corneal edema and visual impairment. In this study, we characterize the impact of CHED-/FECD4-associated SLC4A11 mutations on CEnC function and SLC4A11 protein localization by generating and comparing human CEnC (hCEnC) lines expressing wild type SLC4A11 (SLC4A11WT) or mutant SLC4A11 harboring CHED-/FECD4-associated SLC4A11 mutations (SLC4A11MU). SLC4A11WT and SLC4A11MU hCEnC lines were generated to express either SLC4A11 variant 2 (V2WT and V2MU) or variant 3 (V3WT and V3MU), the two major variants expressed in ex vivo hCEnC. Functional assays were performed to assess cell barrier, proliferation, viability, migration, and NH3-induced membrane conductance. We demonstrate SLC4A11-/- and SLC4A11MU hCEnC lines exhibited increased migration rates, altered proliferation and decreased cell viability compared to SLC4A11WT hCEnC. Additionally, SLC4A11-/- hCEnC demonstrated decreased cell-substrate adhesion and membrane capacitances compared to SLC4A11WT hCEnC. Induction with 10mM NH4Cl led SLC4A11WT hCEnC to depolarize; conversely, SLC4A11-/- hCEnC hyperpolarized and the majority of SLC4A11MU hCEnC either hyperpolarized or had minimal membrane potential changes following NH4Cl induction. Immunostaining of primary hCEnC and SLC4A11WT hCEnC lines for SLC4A11 demonstrated predominately plasma membrane staining with poor or partial colocalization with mitochondrial marker COX4 within a subset of punctate subcellular structures. Overall, our findings suggest CHED-associated SLC4A11 mutations likely lead to hCEnC dysfunction, and ultimately CHED, by interfering with cell migration, proliferation, viability, membrane conductance, barrier function, and/or cell surface localization of the SLC4A11 protein in hCEnC. Additionally, based on their similar subcellular localization and exhibiting similar cell functional profiles, protein isoforms encoded by SLC4A11 variant 2 and variant 3 likely have highly overlapping functional roles in hCEnC.

Sleep Disturbances and Hygiene of Adolescent Female Survivors of Domestic Minor Sex Trafficking.

INTRODUCTION: This cross-sectional quantitative study investigated the sleep hygiene and disturbances of adolescent female survivors of domestic minor sex trafficking (DMST) compared to an online sample of community-dwelling adolescent females. METHOD: Community-dwelling adolescent females (aged 13-17 years, n = 61) and survivors of DMST housed in residental care (aged 12-17 years, n = 19) completed the Children's Report of Sleep Patterns (adolescent version). Descriptive statistics on sleep health in both samples were computed and compared using chi-square and t-tests. RESULTS: Among the survivors of DMST, the majority reported insufficient sleep duration, okay-to-poor sleep quality, waking thirsty, and frequent nightmares. Compared with community-dwelling adolescents, survivors of DMST had more symptoms of insomnia, sleepiness, nightmares, and waking thirsty (p < .05). DISCUSSION: Sleep disturbances among adolescent female survivors of DMST may be more prevalent than in community-dwelling adolescent females. Further empirical research on appropriate assessment and trauma-informed treatment of sleep in this population is needed.

The Performance of Freestyle Libre Pro Flash Continuous Glucose Monitoring in Hospitalized Patients Treated with an Intravenous Insulin Infusion for Acute Prednisolone-Induced Hyperglycemia.

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion.

Cardiovascular Risk Markers in Adults With Adrenal Incidentaloma and Mild Autonomous Cortisol Secretion.

CONTEXT: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. OBJECTIVE: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. DESIGN: Cross-sectional study. PATIENTS: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. METHODS: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. MAIN OUTCOME MEASURE: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. RESULTS: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. CONCLUSION: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality.

Visual Outcomes Following Surgical Debulking in Exophytic Optic Nerve Sheath Meningiomas.

PURPOSE: To report a case of a globular primary optic nerve sheath meningioma managed surgically with improvement in vision and review the literature for outcomes of purely intraorbital exophytic-globular primary optic nerve sheath meningiomas managed surgically. METHODS: A literature review was conducted using Google Scholar and PubMed with the search terms "primary optic nerve sheath meningioma," "surgery," "exophytic," and "globular." Articles were included if they were available in English. Individual cases from the reviewed articles were included if the tumor was purely intraorbital with a globular or exophytic morphology, was managed with total or subtotal surgical excision, and visual outcomes were reported. Cases were excluded if the tumor extended intracanalicularly or intracranially, tumor morphology was unknown, or surgical management consisted of biopsy, optic nerve sheath decompression, or optic canal decompression rather than tumor debulking. RESULTS: A total of 28 patients with intraorbital globular-exophytic primary optic nerve sheath meningiomas managed surgically have been reported in the literature. Vision improved in 29% (n = 8/28) and remained stable in 43% (n = 12/28) of patients. Furthermore, patients with good (Snellen notation ≥ 0.5) vision (n = 10) typically retained good vision postoperatively and at follow-up, with 1 patient experiencing a decline to poor (Snellen ≤0.1) vision at the last follow-up (92 months postoperatively). Similarly, patients with fair (Snellen notation >0.1 and <0.5) vision (n = 5) often improved to good vision (n = 3) or stayed at fair vision (n = 1), with 1 declining to poor vision at postoperative hospital discharge. CONCLUSIONS: Surgical management of exophytic or globular optic nerve meningiomas does not universally lead to vision loss and may be appropriate in select patients.

The Long Road to Develop Custom-built Livers: Current Status of 3D Liver Bioprinting.

Although liver transplantation is the gold-standard therapy for end-stage liver disease, the shortage of suitable organs results in only 25% of waitlisted patients undergoing transplants. Three-dimensional (3D) bioprinting is an emerging technology and a potential solution for personalized medicine applications. This review highlights existing 3D bioprinting technologies of liver tissues, current anatomical and physiological limitations to 3D bioprinting of a whole liver, and recent progress bringing this innovation closer to clinical use. We reviewed updated literature across multiple facets in 3D bioprinting, comparing laser, inkjet, and extrusion-based printing modalities, scaffolded versus scaffold-free systems, development of an oxygenated bioreactor, and challenges in establishing long-term viability of hepatic parenchyma and incorporating structurally and functionally robust vasculature and biliary systems. Advancements in liver organoid models have also increased their complexity and utility for liver disease modeling, pharmacologic testing, and regenerative medicine. Recent developments in 3D bioprinting techniques have improved the speed, anatomical, and physiological accuracy, and viability of 3D-bioprinted liver tissues. Optimization focusing on 3D bioprinting of the vascular system and bile duct has improved both the structural and functional accuracy of these models, which will be critical in the successful expansion of 3D-bioprinted liver tissues toward transplantable organs. With further dedicated research, patients with end-stage liver disease may soon be recipients of customized 3D-bioprinted livers, reducing or eliminating the need for immunosuppressive regimens.

The Role of Preprocedure Genetic Counseling in Pregnancies Interrupted for Fetal Abnormalities.

OBJECTIVE: Congenital birth defects affect 3 to 5% of pregnancies. Genetic counseling can help patients navigate the testing process and understand results. The study objective was to identify predictors and utility of genetic counseling at the time of pregnancy termination. Additionally, we aimed to see what proportion of patients would benefit from additional testing based on the results of the genetic testing. STUDY DESIGN: This was a retrospective cohort review of all terminations performed for fetal anomalies by an academic center from July 2016 to May 2020. Indications were stratified by abnormal serum screening or types of abnormal ultrasound findings. Data were abstracted regarding uptake of genetic counseling and testing results. Abnormal results that warranted additional testing regarding recurrence risks were noted. Multivariable logistic regression was performed to identify predictors of receipt of genetic counseling and testing. RESULTS: Of 387 patients, 57% (n = 220) received preprocedure genetic counseling and 43% (n = 167) did not. Among patients who received diagnostic testing, 62% (n = 194) had genetic counseling compared with 38% (n = 121) without counseling (adjusted odds ratio 2.46, 95% confidence interval [1.41-4.29], p < 0.001). Among the entire cohort, 38% (n = 148) had suspected aneuploidy based on serum screening. Of these, 89% (n = 132/148) had definitive testing, 92% (n = 122/132) confirming the aneuploidy. Among the other 68% (n = 239) with structural anomalies, 76% (n = 183) had diagnostic testing with 29% (n = 53) yielding an abnormal result. Among those fetuses with structural anomalies, 36% (n = 19/53) of genetic diagnoses warranted additional parental testing because of risk of recurrence compared with only 2% (n = 2/122) of patients with abnormal serum screening results alone. CONCLUSION: Genetic counseling was associated with increased uptake of diagnostic testing, which yielded useful information and prompted additional testing. This is important for determining etiology and recurrence risk and should be offered to patients presenting for termination for fetal indications, as well as providing diagnostic closure for patients. KEY POINTS: · Genetic counseling increases the uptake of diagnostic testing in patients with fetal anomalies.. · Patients with ultrasound anomalies received less diagnostic testing despite actionable results 36% of the time.. · Genetic testing is invaluable for recurrence risk counseling even if patients chose to terminate..

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to Treating Stage 2 Type 1 Diabetes.

OBJECTIVE: Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA1c in new-onset stage 3 type 1 diabetes, yet efficacy in delaying progression from stage 2 to stage 3 has not been evaluated. RESEARCH DESIGN AND METHODS: Children (n = 6) aged 5-14 years with stage 2 type 1 diabetes received off-label, low-dose ATG. HbA1c, C-peptide, continuous glucose monitoring, insulin requirements, and side effects were followed for 18-48 months. RESULTS: Three subjects (50%) remained diabetes free after 1.5, 3, and 4 years of follow-up, while three developed stage 3 within 1-2 months after therapy. Eighteen months posttreatment, even disease progressors demonstrated near-normal HbA1c (5.1% [32 mmol/mol], 5.6% [38 mmol/mol], and 5.3% [34 mmol/mol]), time in range (93%, 88%, and 98%), low insulin requirements (0.17, 0.18, and 0.34 units/kg/day), and robust C-peptide 90 min after mixed meal (1.3 ng/dL, 2.3 ng/dL, and 1.4 ng/dL). CONCLUSIONS: These observations support additional prospective studies evaluating ATG in stage 2 type 1 diabetes.

Discovery and characterization of novel TRPML1 agonists.

Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.

Red-Colored Circularly Polarized Luminescence from a Benzo-Fused BODIPY-BINOL Complex.

Red emission with sharp bandwidth and high quantum yield is a desired characteristic for organic chromophores in optoelectronic, spintronic, and biomedical applications. Here, we observe circularly polarized luminescence (CPL) with these characteristics from a benzo-fused BODIPY-BINOL complex (1). Using time-resolved optical spectroscopy, electrochemistry, and density functional theory calculations, we showed that the emissive excited state of 1 does not have a charge-transfer (CT) character, unlike that of the regular BODIPY counterpart (2). The rigidity and the lack of CT character make this class of molecules an appealing platform for CPL-active molecules in the red spectral region, with ample room for improvement in the dissymmetry factor and brightness.