Neighborhood disadvantage, race, and clinical outcomes in neuromyelitis optica spectrum disorder.

BACKGROUND: Little is known about the relationship between neighborhood disadvantage and neuromyelitis optica spectrum disorder (NMOSD) outcomes. OBJECTIVE: The objective is to determine the impact of neighborhood disadvantage on time from symptom onset to diagnosis and annualized relapse rate (ARR). METHODS: Neighborhood disadvantage were captured with the Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage. Negative binomial regression models assessed the impact of ADI on diagnostic delay (⩾3 months between symptom onset and diagnosis) and ARR. RESULTS: A total of 158 NMOSD patients were identified, a majority of whom were White (56.3%) and female (89.9%) with a mean age of 46 years at diagnosis. The ADI did not significantly affect odds of diagnostic delay (odds ratio (OR) = 0.99, p = 0.26). In univariable models, the ADI was not significantly associated with ARR (OR = 1.004, p = 0.29), but non-White race (OR = 1.541, p = 0.02) and time on immunosuppressive therapies (ISTs; OR = 0.994, p = 0.03) were. White patients used IST for an average of 81% of the follow-up period, compared to an average of 65% for non-White patients (p < 0.01). CONCLUSION: No significant relationship between neighborhood-level disadvantage and diagnostic delay or ARR in NMOSD patients was observed. Non-White patients had a higher ARR, which may be related to less IST use.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Development of reference intervals for serum biochemistry and haematology of juvenile green sea turtles (Chelonia mydas) in a Thai rehabilitation centre.

No reference intervals for serum biochemistry and haematology of sea turtles in Thailand exists to assist veterinarians who are responsible for sea turtle health management and treatment. This study determined serum biochemistry and basic haematology of healthy juvenile green sea turtles (n = 92) in captivity in Thailand following the American Society for Veterinary Clinical Pathology (ASVCP), Quality Assurance and Laboratory Standards Committee (QALS) guidelines for the determination of reference intervals in veterinary species. Biochemistry tests, including blood urea nitrogen, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were analysed using an IDEXX VetTest Chemistry Analyzer. Haematology parameters were measured manually using a microhaematocrit for packed cell volume (PCV), Neubauer counting chamber for red blood cell count and cyanmethemoglobin method for haemoglobin concentration. mean corpuscular volume and mean corpuscular haemoglobin concentration were calculated using the PCV, red blood cell count and haemoglobin. Turtles in this study were found to have higher mean values for PCV (28.70%), haemoglobin (92.13 g/L), mean corpuscular haemoglobin concentration (327.03 g/L), uric acid (247.15 µmol/L), alanine aminotransferase (16.53 IU/L), aspartate aminotransferase (209.44 IU/L), and alkaline phosphatase (245.08 IU/L) compared to sea turtles in Brazil. The reference intervals established using high numbers of healthy turtles in this study will assist veterinarians with diagnostic and treatment decisions when evaluating laboratory results for juvenile green sea turtles.

Standardization of a silver stain to reveal mesoscale myelin in histological preparations of the mammalian brain.

BACKGROUND: The brain is built of neurons supported by myelin, a fatty substance that improves cellular communication. Noninvasive magnetic resonance imaging (MRI) is now able to measure brain structure like myelin and requires histological validation. NEW METHOD: Here we present work in small and large biomedical model mammals to standardize a silver impregnation method as a high-throughput histological myelin visualization procedure. Specifically, we built a new staining well plate to increase batch size, and then systematically varied the staining and clearing cycles to describe the staining response curve across taxa and conditions. We compared tissues fixed by immersion or perfusion, mounted versus free-floating, and cut as thicker or thinner slices, with two-weeks of post-fixation. RESULTS: The staining response curves show optimal staining with a single exposure across taxa when incubation and clearing epochs are held to within 3-9 min. We show that clearing was slower in mounted vs free-floating tissue, and that staining was faster and caused fracturing earlier in thinner sliced and smaller volumes of tissue. COMPARISON WITH EXISTING METHODS: We developed a batch processing approach to increase throughput while ensuring reproducibility and demonstrate the optimal conditions for fine myelinated fiber morphology visualization with short cycles (<9 minutes). CONCLUSIONS: We present our optimized protocol to reveal mesoscale neuroanatomical myelin content in histology across mammals. This standard staining procedure will facilitate multiscale analyses of myelin content across development as well as in the presence of injury or disease.

Improving Safety through a Virtual Learning Collaborative.

Background: Frontline healthcare safety leaders require expertise and confidence to manage local safety programs effectively yet are confronted with substantial challenges in identifying risk and reducing harm. Methods: We convened a multidisciplinary safety learning collaborative in a children's hospital pediatric department and used the Institute for Healthcare Improvement's Breakthrough Series model. Participants attended four virtual education sessions over 13 months (September 2020-September 2021) focused on identifying harm and using tools to improve safety. We analyzed departmental safety data monthly throughout the collaborative. The primary outcome was the development of improvement projects using direct application of the session content. The secondary outcome was participant confidence in improving safety via pre- and postsurveys. Results: Seventy clinicians and quality consultants participated. Fifteen divisional safety improvement projects were initiated. The percentage of survey respondents who reported feeling "completely confident" in their ability to improve safety increased from 26% (n = 39) to 58% (n = 26) from September 2020 to September 2021 (P = 0.01) and maintained at 65% 1 year after the end of the collaborative. We observed a decrease in the mean rate of reported inpatient preventable and possibly preventable moderate/serious/catastrophic events per 1000 bedded days from 1.10 (baseline) to 0.71 (intervention period). Conclusions: Through a collaborative effort in a virtual learning environment, we facilitated the development of fifteen safety projects, increased leaders' confidence in improving safety, and saw improved inpatient safety. This approach, which involves healthcare professionals from various disciplines, may be effectively adapted to other settings.

CTAD Task Force Paper: Neuropsychiatric Symptoms in AD: Clinical Trials Targeting Mild Behavioral Impairment: A Report from the International CTAD Task Force.

The International CTAD Task Force (TF) addressed challenges related to designing clinical trials for agitation in dementia, presenting accomplishments from the two previous TFs on neuropsychiatric symptoms (NPS). In addition, this TF proposed a paradigm shift in NPS assessment and management, presenting Mild Behavioral Impairment (MBI) as a clinical syndrome. MBI is marked by later-life emergent and persistent NPS in dementia-free older persons (ranging from cognitively unimpaired to subjective cognitive decline to mild cognitive impairment), which facilitates earlier detection and better prognostication of Alzheimer's disease (AD). The TF has made the following recommendations for incorporation of NPS into AD preventative trials: (1) clinical trials targeting improvement in MBI symptoms should be undertaken; (2) treatment trials for MBI should be disease specific and confirm the diagnosis of participants using biomarkers; trials should include measures sensitive to cognitive changes in preclinical AD, which can serve as outcome measures, in addition to changes in biomarker levels; (3) as a first step, pharmacotherapeutic trials should address the full MBI complex as well as the specific symptoms/domains that constitute MBI; (4) clinical trials using problem-adaptation psychotherapy to target affective MBI should be considered; and (5) MBI should be considered in AD trials of disease modifying therapies. The well-validated and widely-used MBI Checklist (MBI-C) is an appropriate symptom rating scale for these studies, as it was developed specifically to identify and measure MBI in dementia-free persons. Other scales such as the Neuropsychiatric Inventory (NPI) may be used, although administration at two timepoints may be necessary to operationalize the MBI criterion of symptom persistence.

Novel Antimitotic Agent SP-1-39 Inhibits Head and Neck Squamous Cell Carcinoma.

Effective management of head and neck cancer (HNC) poses a significant challenge in the field of oncology, due to its intricate pathophysiology and limited treatment options. The most common HNC malignancy is head and neck squamous cell carcinoma (HNSCC). HNSCC treatment includes a combination of surgery, radiation, and chemotherapy. While HNSCC is treatable if diagnosed early, this is often not the case and is considered incurable once in its late stages and metastatic disease has developed. Therapies are also limited once resistant disease has occurred. SP-1-39, a novel colchicine-binding site inhibitor (CBSI), has been recently reported for its potential efficacy in a variety of cancer cell lines including breast, melanoma, pancreatic, and prostate. SP-1-39 also shows abilities to overcome paclitaxel resistance in a paclitaxel-resistant prostate cancer xenograft model. To evaluate the potential of SP-1-39 as a new HNSCC treatment option, herein we systematically performed preclinical studies in HNSCC models using SP-1-39 and demonstrated that, in vitro, SP-1-39 inhibits the proliferation of 2 HNSCC cell lines with low nanomolar IC50 values (1.4 to 2.1 nM), induces HNSCC cell apoptosis in a dose-dependent manner, interferes with migration of HNSCC cells, and leads to HNSCC cell cycle arrest in the G2/M phase. In vivo, SP-1-39 suppresses the primary tumor growth of a Detroit 562 subcutaneous xenograft mouse model in 6- to 8-wk-old, male NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, with no detectable cytotoxic effects at a low dose of 2.5 mg/kg. This efficacy of SP-1-39 is better when compared with the treatment using a reference chemotherapy drug, paclitaxel at 10 mg/kg. Collectively, these data demonstrate that SP-1-39 is a promising candidate for further development for more efficacious HNSCC treatment.

Is tropical spastic paraparesis in West Indian-Born U.K. migrants caused by HTLV-I? - abstract

Of 13 patients of West Indian origin residing in the UK with paraparesis of unknown cause, all had serum antibody to human T-Cell lymphotropic virus type I (HTLV-I). Their magnetic resonance imaging (MRI) scans were normal or showed only minor abnormalities in the brain, and the spinal cord was normal in 5 that were imaged. This is in marked contrast to the MRI scans in patients with multiple sclerosis (MS). None of 50 patients with MS had antibody to HTLV-I in the blood (AU)

Antibody to human T-lymphotropic virus type 1 in West-Indian-born UK residents with spastic paraparesis

Of 13 West-Indian-born UK residents with spastic paraparesis of unknown cause, 11 were tested for serum antibody to human T-cell lymphotropic virus type 1 and all were positive. Their magnetic resonance imaging scans were normal or showed only minor abnormalities in the brain, and the spinal cord was normal in the 5 investigated. Of 48 patients with multiple sclerosis, mainly caucasian, none had antibody to HTLV-1 in the blood.(AU)