Longitudinal evaluation of pediatric and young adult metabolic dysfunction-associated steatotic liver disease defined by MR elastography.

OBJECTIVES: To inform clinical monitoring of children and young adults with metabolic dysfunction-associated steatotic liver disease (MASLD) by characterizing the real-world natural history of MASLD and identifying baseline predictors of liver disease progression. MATERIALS AND METHODS: This retrospective study included consecutive patients ages < 23 years with MASLD who underwent serial MR elastography (MRE) and/or MR fat fraction (FF) examinations between 09/2009 and 11/2022. Outcomes of MASLD were defined based on maximum ratio values. A relative change ≥ 19% in liver stiffness measures (LSM) and an absolute change ≥ 5% for liver FF were considered clinically meaningful. Random intercept models characterized the yearly rate of change in LSM (kilopascals per year) and FF (percentage per year). RESULTS: One hundred twenty-one patients (87 males, mean age at baseline: 12 ± 3 [SD] years) underwent 297 MRE examinations. The mean interval between the first and last MRE was 34 (± 24) months (range: 1-120 months). Among the 114 patients with serial LSM, 33% (38/114) showed progression, 46% (53/114) remained stable, and 21% (23/114) showed regression. Among the 88 patients with serial FF measures, 57% (50/88) showed progression, 2% (2/88) remained stable, and 41% (36/88) showed regression. LSM progression was associated with Hispanic ethnicity, baseline BMI-for-age percentile, baseline mean liver FF, and GGT changes over time. Predictors for liver FF progression included ALT, AST, GGT, and LDL. CONCLUSION: In a real-world sample of children and young adults with MASLD who underwent serial liver MRI, a minority of patients demonstrated improvements in liver stiffness or FF over time. KEY POINTS: Question In children, there is scarce data regarding the natural history of MASLD. Findings In this retrospective study, most children and young adults with MASLD had either unchanged or worsening liver stiffness (n = 91/114, 79%) and liver fat (n = 52/88, 59%). Clinical relevance Our findings emphasize the need for optimized care in pediatric MASLD. The identified risk factors for the progression of liver fat and stiffness may help to identify children who require interventions beyond changes in lifestyle.

Randomized pilot trial of an unconditional cash transfer intervention to address food insecurity in oncology.

Screening for food insecurity and other social determinants of health is being integrated into oncology practice. We performed a pilot randomized trial to investigate whether an unconditional cash transfer (UCT) could be used to address food insecurity among female breast and gynecologic cancer survivors. Food insecure cancer survivors completed a baseline survey and were randomized to receive $100/month for three months (UCT) or usual care (UC). Participants (n = 14) completed a follow-up survey after 3-months and we compared changes in health-related quality of life, indicators of food insecurity, diet quality, and whether a participant had to forgo, delay, or make changes to medical care because of cost. The UCT was associated with higher physical health scores, fewer indicators of food insecurity, better diet quality, and a lower likelihood of forgoing medical care than those who received UC. Our results suggest that UCTs can improve outcomes for food insecure cancer survivors.

A Guide for Nurse-Led Advocacy for Safe Staffing and the Quality of Nursing Work Life.

Nursing advocacy is a critical component of nursing practice. An exemplar of how nurses can advocate for an enhanced quality of nursing work environment and safe staffing is provided. Garnering state and national resources can assist in impacting statewide change. [J Contin Educ Nurs. 2024;55(11):520-522.].

Metabolomic Changes Associated with AGXT2 Genotype Variants and Stone Formation in a Colony of Cats.

OBJECTIVE: The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats with uroliths. METHODS: AGXT2 genotypes of 445 cats in the colony at Hill's Pet Nutrition, Inc. (Topeka, KS, USA) were assessed in a genome-wide association study. Additionally, the serum chemistries and metabolic profiles of each cat were determined, along with their lifetime history of stone incidence. Factor analysis was used as a data-reduction method for metabolites in order to perform statistical hypothesis testing and to select significant metabolites from the more than 600 serum metabolites identified. RESULTS: Of the 82 cats forming stones in the colony (18.4%), the majority were calcium oxalate. Results showed that approximately one third of the cats with the AA variant of the AGXT2 gene have stones, that chronic kidney disease (CKD) is more common in cats with stones, and that having stones results in a shorter lifespan. A discriminant variable selection process was performed to determine the complete blood count, serum biochemistries, and serum metabolomic factors that best discriminated among the three genotypes (AA, AG, GG) and between cats forming stones and non-stone formers. Several of the highly ranked discriminating factors included metabolites related to decreased aminotransferase activity in cats with the AA variant of the AGXT2 gene. Another factor that ranked highly for discriminating between stone formers and non-stone formers contained lipid metabolites, consisting of multiple sphingomyelin species and cholesterol. CONCLUSIONS: These findings support the results of feeding studies in cats, whereby CKD cats fed food supplemented with betaine and prebiotics have experienced an increase in total body mass, reduced uremic toxins, and altered sphingomyelin concentrations.

Identification and Characterization of Novel Serpentoviruses in Viperid and Elapid Snakes.

Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be subclinical or associated with oral and/or respiratory disease. Beginning in June 2019, a population of over 150 confiscated snakes was screened for serpentovirus as part of a quarantine disease investigation. Antemortem oropharyngeal swabs or lung tissue collected postmortem were screened for serpentovirus by PCR, and 92/165 (56.0%) of snakes tested were positive for serpentovirus. Serpentoviruses were detected in fourteen species of Viperidae native to Asia, Africa, and South America and a single species of Elapidae native to Australia. When present, clinical signs included thin body condition, abnormal behavior or breathing, stomatitis, and/or mortality. Postmortem findings included variably severe inflammation, necrosis, and/or epithelial proliferation throughout the respiratory and upper gastrointestinal tracts. Genetic characterization of the detected serpentoviruses identified four unique viral clades phylogenetically distinct from recognized serpentovirus genera. Pairwise uncorrected distance analysis supported the phylogenetic analysis and indicated that the viper serpentoviruses likely represent the first members of a novel genus in the subfamily Serpentovirinae. The reported findings represent the first documentation of serpentoviruses in venomous snakes (Viperidae and Elapidae), greatly expanding the susceptible host range for these viruses and highlighting the importance of serpentovirus screening in all captive snake populations.

Consumption of Low-Calorie Sweeteners among Children Aged 6 Months to 5 Years in the United States, NHANES 2017-2020.

BACKGROUND: Although the American Academy of Pediatrics advises against low-calorie sweeteners (LCS) consumption by children <5 y due to potential health and development concerns, the extent of this consumption among these children is unknown. OBJECTIVES: The objective of this study was to describe the intake, sources, and dietary patterns associated with LCS consumption among United States infants and preschoolers. METHODS: We used cross-sectional 24-h dietary recall data (day 1) among 1497 children aged 6 mo to 5 y from the National Health and Nutrition Examination Survey 2017-2020 prepandemic. Complex survey procedures and sampling weights were applied to compare LCS consumption patterns (prevalence and frequency [times/day] of any LCS, any LCS-containing beverages [LCSBs], and any LCS-containing foods [LCSFs], with each occurrence of consumption = 1 "serving") across demographic subgroups and to assess the associated nutrients and % of total energy intake (TEI). RESULTS: Thirty-one percent of children aged 6 mo to 5 y consumed ≥1 LCSB and/or LCSF on a given day. The prevalence of LCS consumption increased with age, 10.5% (6 to <12 mo) to 34.3% (2-5 y). Among LCS consumers, mean serving frequency was 1.4 times/d, with no differences by age or sex. Of all LCSBs servings consumed, 64.0% were fruit drinks; 57.8% of all LCSFs servings were non-Greek yogurt. As consumption levels increased from no LCS to >1 serving/d, intake of the following also increased: total sugar (+1.8% TEI, P-trend = 0.04), added sugar (+1.1%, P-trend = 0.048), sodium (+304 mg, P-trend = 0.04), and fiber (+0.8 g, P-trend = 0.01). In contrast, protein intake was lower (-0.7% TEI, P-trend = 0.02). Those consuming 1 LCS serving/d consumed more total energy than LCS nonconsumers (1606 compared with 1401 kcal), but TEI did not increase further with >1 LCS serving/d (1607 kcal). LCS consumption was not associated with carbohydrate or fat intake. CONCLUSIONS: LCS consumption, primarily from fruit drinks and non-Greek yogurt, is prevalent among United States preschoolers, and this consumption is associated with greater intake of total sugar, added sugar, and sodium.

Characteristics and real-world outcomes of patients with epithelial ovarian cancer who received niraparib plus bevacizumab first-line maintenance therapy in the COMB1NE study.

OBJECTIVE: In the phase 2 OVARIO trial (NCT03326193) investigating niraparib-bevacizumab first-line maintenance, median progression-free survival was 14.2 months (95% confidence interval (CI) 8.6 to 16.8) for patients with homologous recombination (HR)-proficient (HRp) epithelial ovarian cancer, and 12.1 months (95% CI8.0-not evaluated) for patients with undefined HR status. However, real-world data are limited for patients who receive niraparib-bevacizumab first-line maintenance therapy. The COMB1NE study describes real-world clinical outcomes (time to treatment discontinuation; time to next treatment) in patients with epithelial ovarian cancer who received niraparib-bevacizumab first-line maintenance, regardless of first-line bevacizumab use. METHODS: This real-world, retrospective study used a US nationwide electronic health record-derived deidentified database. Eligible patients were 18 years or older at initial epithelial ovarian cancer diagnosis and initiated niraparib-bevacizumab first-line maintenance (January 1, 2017-September 2, 2022) following first-line treatment. The index date was the start of first-line maintenance. Patients were followed until death, last clinical activity, or end of study, whichever occurred first. Time to treatment discontinuation and time to next treatment, a proxy for real-world progression-free survival, were estimated using the Kaplan-Meier method. RESULTS: Among 59 included patients, the median age was 67 years (interquartile range (IQR) 61-76), and 81.4% had stage III/IV epithelial ovarian cancer at diagnosis. Overall, 83.1% of patients had BRCA wild-type with either HRp or HR status unknown disease. Median time to treatment discontinuation of first-line maintenance was 11.8 months (95% CI 8.7 to 13.5). Median time to next treatment was 14.1 months (95% CI 11.3 to 16.6). At 6 months after index, 77.9% of patients had not initiated second-line treatment; at 12 months, 61.3% had not. CONCLUSION: In this real-world study of patients receiving niraparib-bevacizumab first-line maintenance, the majority of whom had HRp/HR status unknown, the median time to next treatment was consistent with observed progression-free survival in patients with similar HR status in the OVARIO study.

The Foundation to Advance Brain Rehabilitation: Organization, History, and Collaborative Database.

OBJECTIVE: To describe the history, organization, goals, and data management procedures of the Foundation to Advance Brain Rehabilitation (FABR). SETTING: Postacute brain injury rehabilitation following acute inpatient care. KEY POINTS: FABR was incorporated in 2019 with a primary mission to advance brain rehabilitation through scientific and strategic analysis of industry-wide data. Contributing FABR member organizations include Bancroft NeuroRehab, Collage Rehabilitation Partners, On With Life, Pate NeuroRehabilitation, and Shepherd Center. These organizations contribute demographic, admission, discharge, and follow-up data on persons served in 5 types of intensive posthospital brain injury rehabilitation programs (neurobehavioral residential, neurorehabilitation residential, home and community neurorehabilitation, day treatment, and outpatient) and 3 types of supported living programs (neurobehavioral residential, residential, and community-based) to a collaborative database managed by Inventive Software Solutions. Inventive Software Solutions provides FABR researchers with a dataset that is de-identified both for participant and organizational identifying information.

Medical Malpractice in Otolaryngology within the United States: A LexisNexis-Based Demographic Analysis.

OBJECTIVE: Otolaryngologists are at a significantly greater risk of being sued than most other physicians. To date, there is a lack of studies characterizing trends in otolaryngology malpractice claims. To assess these trends and risk variables, this study examined malpractice claims against otolaryngologists. STUDY DESIGN: Retrospective database review. SETTING: LexisNexis Jury Verdicts and Settlements. METHODS: The LexisNexis legal database was used to locate jury verdicts and settlements related to medical malpractice in otolaryngology, from 2018 to 2024. The study did not include any claims covered by the Social Security Disability Insurance, Workers' Compensation, Healthcare Law, or Criminal Law and Procedure categories. Temporal trends were evaluated, and logistic regression was used to identify independent risk factors. RESULTS: Out of 903 items, 79 reported malpractice cases were included (mean age 44.5; 60.3% female). The most sued subspecialty was head and neck oncology (32.5%). Negligence (93.7%) was the primary cause of action. Of cases sent to the jury, 87.7% of them resulted in a verdict in favor of the defendant. The mean plaintiff verdict payout was $7,432,508.06 and the mean identified settlement amount was $1,562,500.00. Physical injury (62.0%) was the highest type of harm. Regional analysis indicated a higher percentage of cases from New York favored the defendant (21.1% vs 13.6%; P = .034). CONCLUSION: This study highlights key trends in otolaryngology malpractice claims, emphasizing the prevalence in cases of head and neck surgery, primarily attributed to negligence. By identifying trends and risk factors, otolaryngologists can get a better understanding of the dynamics surrounding malpractice.

Oral Pyronaridine Tetraphosphate Reduces Tissue Presence of Parasites in a Mouse Model of Chagas Disease.

The eukaryotic parasite Trypanosoma cruzi (T. cruzi) is responsible for Chagas disease, which results in heart failure in patients. The disease is more common in Latin America, and is an emerging infection with The Centers for Disease Control estimating that greater than 300,000 people are currently infected in the United States. This disease has also spread from South and Central America, where it is endemic to many other countries, including Australia, Japan, and Spain. Current therapy for Chagas disease is inadequate due to limited efficacy in the indeterminate and chronic phases of the disease, in addition to the adverse effects from nifurtimox and benznidazole, which are nitro-containing drugs used for therapy. There is a clear need for new therapies for the Chagas disease. Using a computational machine learning approach, we have previously shown that the antimalarial pyronaridine tetraphosphate is active against T. cruzi Brazil-luc in vitro against parasites infecting a myoblast cell line and is also active in vivo in an acute mouse model of Chagas disease when dosed i.p. We now further evaluated oral pyronaridine as a monotherapy to determine the minimum effective dose to treat acute and chronic models of Chagas disease. Our results for T. cruzi Brazil-luc demonstrated daily oral dosing with pyronaridine from 150 to 600 mg/kg resulted in statistically significant inhibition in the 7 day acute mouse model. Combination therapy with daily dosing of benznidazole and pyronaridine in the acute infection model demonstrated that 300 mg/kg pyronaridine could return statistically significant antiparasitic activity to a subtherapetic 10 mg/kg benznidazole. In contrast, pyronaridine as monotherapy or combined with benznidazole lacked efficacy in the chronic mouse model, whereas 100 mg/kg benznidazole alone demonstrated undetectable parasites in the heart of mice. Pyronaridine requires further assessment in other chronic models to identify if it can be used beyond the acute stage of T. cruzi infection.

Colonoscopy quality measures and adherence to follow-up guidelines among endoscopists participating in a U.S. endoscopy registry.

BACKGROUND AND AIMS: Colonoscopy screening can substantially reduce colorectal cancer incidence and mortality. Colonoscopies may achieve maximum benefit when they are performed with high quality and accompanied by follow-up recommendations that adhere to clinical guidelines. This study aimed to determine to what extent endoscopists met targets for colonoscopy quality from 2016 through 2019 (the most recent years before the COVID-19 pandemic). METHODS: We examined measures of colonoscopy quality and recommended follow-up intervals in the GI Quality Improvement Consortium, a large nationwide endoscopy registry. The analysis included >2.5 million outpatient screening colonoscopies in average-risk adults aged 50 to 75 years. RESULTS: At least 90% of endoscopists met performance targets for adequate bowel preparation, cecal intubation rate, and adenoma detection rate. However, nonadherence to guidelines for follow-up intervals was common. For patients with no colonoscopy findings, 12.0% received a follow-up interval recommendation of ≤5 years instead of the guideline-recommended 10 years. For patients with 1 to 2 small tubular adenomas, 13.5% received a follow-up interval recommendation of ≤3 years instead of the guideline-recommended 5 to 10 years. For patients with small sessile serrated polyps, 30.7% received a follow-up interval recommendation of ≤3 years instead of the guideline-recommended 5 years. Some patients with higher risk findings received a follow-up interval recommendation of ≥5 years instead of the guideline-recommended 3 years, including 18.2% of patients with advanced serrated lesions. CONCLUSIONS: Additional attention may be needed to achieve more consistent adherence to guidelines for colonoscopy follow-up recommendations.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

INTRODUCTION: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. METHODS: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. RESULTS: Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. CONCLUSION: This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.

Outcomes of Patients with Myeloid Malignancies and Cardiovascular Disease Undergoing Allogeneic Stem Cell Transplantation.

INTRODUCTION/BACKGROUND: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications. METHODS: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GvHD) were compared in patients with and without CV risk factors or disease. RESULTS: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs. 60%, p = 0.001) and unrelated donors (56% vs. 35%, p = 0.04). Early adverse cardiac events occurred more frequently in the CVD versus no-CVD group (38% vs. 14%), particularly arrhythmias (21% vs. 5%; p = 0.04). CVD patients tended to have poorer OS and PFS outcomes (HR = 1.98, [1.00, 3.92]; HR = 1.89, [0.96-3.72], respectively). OS rate at 1, 2, and 3 years for CVD versus no-CVD patients was 66% versus 72%, 55% versus 64%, and 46% versus 62%, respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs. 28%), relapsed disease (32% vs. 52%), and CV events (10% vs. 3%). CONCLUSION: Based on these data, predictive models to identify patients with CVD with higher risk of post-allo-HSCT complications and mortality and strategies to mitigate these risks should be developed.

Simultaneous Multiparameter Mapping of the Liver in a Single Breath-Hold or Respiratory-Triggered Acquisition Using Multi-Inversion Spin and Gradient Echo MRI.

BACKGROUND: Quantitative parametric mapping is an increasingly important tool for noninvasive assessment of chronic liver disease. Conventional parametric mapping techniques require multiple breath-held acquisitions and provide limited anatomic coverage. PURPOSE: To investigate a multi-inversion spin and gradient echo (MI-SAGE) technique for simultaneous estimation of T1, T2, and T2* of the liver. STUDY TYPE: Prospective. SUBJECTS: Sixteen research participants, both adult and pediatric (age 17.5 ± 4.6 years, eight male), with and without known liver disease (seven asymptomatic healthy controls, two fibrotic liver disease, five steatotic liver disease, and two fibrotic and steatotic liver disease). FIELD STRENGTH/SEQUENCE: 1.5 T, single breath-hold and respiratory triggered MI-SAGE, breath-hold modified Look-Locker inversion recovery (MOLLI, T1 mapping), breath-hold gradient and spin echo (GRASE, T2 mapping), and multiple gradient echo (mGRE, T2* mapping) sequences. ASSESSMENT: Agreement between hepatic T1, T2, and T2* estimated using MI-SAGE and conventional parametric mapping sequences was evaluated. Repeatability and reproducibility of MI-SAGE were evaluated using a same-session acquisition and second-session acquisition. STATISTICAL TESTS: Bland-Altman analysis with bias assessment and limits of agreement (LOA) and intraclass correlation coefficients (ICC). RESULTS: Hepatic T1, T2, and T2* estimates obtained using the MI-SAGE technique had mean biases of 72 (LOA: -22 to 166) msec, -3 (LOA: -10 to 5) msec, and 2 (LOA: -5 to 8) msec (single breath-hold) and 36 (LOA: -43 to 120) msec, -3 (LOA: -17 to 11) msec, and 4 (LOA: -3 to 11) msec (respiratory triggered), respectively, in comparison to conventional acquisitions using MOLLI, GRASE, and mGRE. All MI-SAGE estimates had strong repeatability and reproducibility (ICC > 0.72). DATA CONCLUSION: Hepatic T1, T2, and T2* estimates obtained using an MI-SAGE technique were comparable to conventional methods, although there was a 12%/6% for breath-hold/respiratory triggered underestimation of T1 values compared to MOLLI. Both respiratory triggered and breath-hold MI-SAGE parameter maps demonstrated strong repeatability and reproducibility. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Longitudinal Changes in Youth Mental Health From Before to During the COVID-19 Pandemic.

Importance: Robust longitudinal studies of within-child changes in mental health associated with the COVID-19 pandemic are lacking, as are studies examining sources of heterogeneity in such changes. Objective: To investigate within-child changes, overall and between subgroups, in youth mental health from prepandemic to midpandemic. Design, Setting, and Participants: This cohort study used longitudinal prepandemic and midpandemic data from the Environmental influences on Child Health Outcomes (ECHO) Program, collected between January 1, 2015, and March 12, 2020 (prepandemic), and between March 13, 2020, and August 31, 2022 (midpandemic). Data were analyzed between December 1, 2022, and June 1, 2024. The sample included 9 US-based observational longitudinal pediatric ECHO cohorts. Cohorts were included if they collected the Child Behavior Checklist (CBCL) School Age version before and during the pandemic on more than 20 participants of normal birth weight aged 6 to 17 years. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: Prepandemic to midpandemic changes in CBCL internalizing, externalizing, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scores were estimated, and differences in outcome trajectories by child sociodemographic characteristics (age, sex, race, ethnicity, and poverty level) and prepandemic mental health problems were examined using established CBCL clinical score thresholds. Results: A total of 1229 participants (mean [SD] age during the pandemic, 10.68 [2.29] years; 625 girls [50.9%]) were included. The sample was socioeconomically diverse (197 of 1056 children [18.7%] lived at ≤130% of the Federal Poverty Level; 635 (51.7%) identified as White, 388 (31.6%) as Black, 147 (12.0%) as multiracial, 40 (3.3%) as another race, and 118 (9.6%) as Hispanic). Generalized linear mixed-effects models revealed minor decreases in externalizing problems (ß = -0.88; 95% CI, -1.16 to -0.60), anxiety (ß = -0.18; 95% CI, -0.31 to -0.05), and ADHD (ß = -0.36; 95% CI, -0.50 to -0.22), but a minor increase in depression (ß = 0.22; 95% CI, 0.10 to 0.35). Youth with borderline or clinically meaningful prepandemic scores experienced decreases across all outcomes, particularly externalizing problems (borderline, ß = -2.85; 95% CI, -3.92 to -1.78; clinical, ß = -4.88; 95% CI, -5.84 to -3.92). Low-income (ß = -0.76; 95% CI, -1.14 to -0.37) and Black (ß = -0.52; 95% CI, -0.83 to -0.20) youth experienced small decreases in ADHD compared with higher income and White youth, respectively. Conclusions and Relevance: In this longitudinal cohort study of economically and racially diverse US youth, there was evidence of differential susceptibility and resilience for mental health problems during the pandemic that was associated with prepandemic mental health and sociodemographic characteristics.

Octadecaneuropeptide, ODN, Promotes Cell Survival against 6-OHDA-Induced Oxidative Stress and Apoptosis by Modulating the Expression of miR-34b, miR-29a, and miR-21in Cultured Astrocytes.

Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides including octadecaneuropeptide (ODN). We have previously reported that ODN rescues neurons and astrocytes from 6-OHDA-induced oxidative stress and cell death. The purpose of this study was to examine the potential implication of miR-34b, miR-29a, and miR-21 in the protective activity of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Flow cytometry analysis showed that 6-OHDA increased the number of early apoptotic and apoptotic dead cells while treatment with the subnanomolar dose of ODN significantly reduced the number of apoptotic cells induced by 6-OHDA. 6-OHDA-treated astrocytes exhibited the over-expression of miR-21 (+118%) associated with a knockdown of miR-34b (-61%) and miR-29a (-49%). Co-treatment of astrocytes with ODN blocked the 6-OHDA-stimulated production of ROS and NO and stimulation of Bax and caspase-3 gene transcription. Concomitantly, ODN down-regulated the expression of miR-34b and miR-29a and rescued the 6-OHDA-associated reduced expression of miR21, indicating that ODN regulates their expression during cell death. Transfection with miR-21-3p inhibitor prevented the effect of 6-OHDA against cell death. In conclusion, our study indicated that (i) the expression of miRNAs miR-34b, miR-29a, and miR-21 is modified in astrocytes under 6-OHDA injury and (ii) that ODN prevents this deregulation to induce its neuroprotective action. The present study identified miR-21 as an emerging candidate and as a promising pharmacological target that opens new neuroprotective therapeutic strategies in neurodegenerative diseases, especially in Parkinson's disease.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer.

BACKGROUND: Transforming growth factor ß-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer. METHODS: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens. Expression levels of cytoplasmic TAK1 by QuPath digital quantification and punctate TAK1 staining was scored using a manual point scoring technique and correlated with clinicopathological features, immune checkpoint expression and cancer-specific survival. Bulk RNA sequencing was performed in specimens to determine mutational profiles and differentially expressed genes. RESULTS: A cohort of 875 patients who had undergone colorectal cancer resection were assessed for TAK1 expression. Higher levels of cytoplasmic TAK1 expression correlated with elevated PD1 and PD-L1 expression (p < 0.010). High punctate TAK1 expression was more commonly identified in poorly differentiated colorectal cancers (p = 0.036), had dysregulated mutational and transcriptional profiles with decreased insulin-like growth factor 2(IGF2) expression (p < 0.010), and independently predicted poor cancer-specific survival (HR 2.690, 95% CI 1.419-5.100, p = 0.002). The association of punctate TAK1 expression and recurrence remained after subgroup analysis for microsatellite-stable colorectal cancer (p = 0.028). DISCUSSION: Punctate TAK1 expression is associated with worse cancer specific survival. TAK1 signalling may be an important pathway to investigate underlying mechanisms for recurrence in microsatellite-stable colorectal cancer.