Objective: Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features. Methods: All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L. Results: The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts. Conclusion We expand the literature on CSF1R-L patients from India by reporting four new cases.

Myopia is a common eye disease among children and adolescents, and it is also a major and common public health problem for children and adolescents worldwide. Although the myopia rate among children and adolescents in different provinces , cities , and regions varies , the incidence of myopia is generally high , showing a trend of high incidence and younger age. Myopia in children and adolescents is closely related to sleep conditions . The sleep time of most children and adolescents in China does not reach the recommended length of time for this age group, and their sleep quality is poor, which affects their study and life. The biological connection and molecular mechanism between sleep and myopia are hot topics in clinical research . This article reviews the epidemiological characteristics of myopia and sleep status in children and adolescents , as well as the biological mechanisms between sleep and myopia , with the aim of providing a theoretical basis for preventing myopia in children and adolescents.

Hemosuccus pancreaticus (HP) is characterized by hemorrhage from the pancreatic duct through the major duodenal papilla. It represents the least common cause of upper gastrointestinal bleeding (UGIB), occurring in approximately 1 in 1,500 cases and predominantly affecting men. A 58-yearold woman with a history of recurrent pancreatitis presented with severe epigastric pain, vomiting, and diarrhea. Laboratory tests revealed hyperamylasemia. Imaging indicated acute necrohemorrhagic pancreatitis with peripancreatic fluid collections. Despite interventions including drainage and antibiotic therapy, she developed massive hematemesis and hemodynamic instability. Computed tomography indicated active bleeding in the peripancreatic region, and angiography confirmed a diagnosis of HP. Embolization of the gastroduodenal artery was performed; however, the patient died of multiorgan failure. HP, although rare, should be considered in patients with chronic pancreatitis and intermittent UGIB. Diagnosing HP can be challenging, requiring collaboration between gastroenterologists and interventional radiologists. Early intervention is crucial due to the high mortality rate associated with severe cases.

Objective: Intestinal remnant chylomicrons (CMs) are involved in cardiovascular residual risk and the atherogenic process. Microsomal triglyceride transfer protein (MTTP) catalyzes the assembly of lipids to apolipoprotein B48, generating CMs. Dysbiosis could alter this behavior. This study investigated the chemical composition of CMs and their associations with intestinal MTTP and gut fat depots in a diet-induced dysbiosis animal model. Methods: Male Wistar rats were fed either a standard diet (control, n=10) or a high-fat high-sucrose diet (HFSD, n=10) for 14 weeks. Measurements included serum glucose, lipid-lipoprotein profile, free fatty acids (FFAs), lipopolysaccharide (LPS) and the Firmicutes/ Bacteroidetes (F/B) ratio in stool samples, via real-time quantitative polymerase chain reaction.Lipid content in isolated CMs (ultracentrifugation d <0.95 g/mL) was assessed, and MTTP, cell intestinal fat content (CIF), histology, apoB mRNA and tight junction (TJ) proteins were analyzed, in intestinal tissue. Results: Compared to control, HFSD rats showed higher levels of LPS, triglycerides (TGs), non-high-density lipoprotein cholesterol (HDL-C) levels, TG/HDL-C ratio, FFAs, and the F/B ratio. HFSD CMs showed increased TG and phospholipids. TJ proteins levels were lower in the HFSD group, while histological scores showed no differences. CIF was increased in the HFSD group. No significant differences in apoB mRNA were found. MTTP expression was higher in the HFSD group, and directly correlated with CM-TG and inversely correlated with CIF. Conclusion Our findings imply that gut TG content may constitute an important determinant of the secretion of TG-rich CMs, promoted by MTTP, with increased atherogenic potential.

Objective: Childhood obesity, affected by dietary choices, increases cardiovascular risk.Obesity is associated with inflammation and altered glucose, iron and lipid metabolism. This study explores connections between dietary habits, plasma fatty acid profile, cardiovascular risk factors and childhood obesity. Methods: We conducted a case-control study including 20 children and adolescents with obesity and 20 controls. Anthropometric parameters and food frequency questionnaires were registered. Glucose metabolism, iron parameters, lipid profile, fatty acids profile, and lipoprotein-associated phospholipase A 2 (Lp-PLA2 ), cholesteryl ester transfer protein and paraoxonase 1 (PON 1) activities were evaluated. Correlation, regression and mediation analyses were performed. Results: The group with obesity consumed more bakery products and less cereals, and presented higher myristic, palmitoleic, margaric and gamma-linolenic acids, along with lower linoleic, arachidic, gadoleic, eicosatrienoic and eicosapentaenoic (EPA) acids (p<0.05). They also exhibited altered glucose metabolism, a more atherogenic lipid profile, higher Lp-PLA2 and lower PON 1 activities (p<0.05). Consumption of several food groups correlated with metabolic alterations. Different correlations between pro-inflammatory, antiinflammatory and obesity-related fatty acids, and cardiometabolic biomarkers were found, including: myristic acid with Lp-PLA2 (r=0.32, p<0.05), EPA acid with hs-CRP (r=−0.36, p<0.05) and gadoleic acid with PON1 (r=0.39, p<0.05). Mediation analyses revealed fatty acids and cardiometabolic markers as mediators of the association between dietary habits and obesity. Conclusion Children and adolescents with obesity presented disrupted glucose and lipid metabolism, vascular inflammation, attenuated antioxidant function and altered fatty acid composition. Direct and indirect associations between dietary habits, fatty acids, cardiometabolic markers and the presence of obesity were found.

Objective: Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features. Methods: All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L. Results: The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts. Conclusion We expand the literature on CSF1R-L patients from India by reporting four new cases.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD. Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixinmeglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg). Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC) 0-72 /MIC ratio with enro-R, and enro-C/Al exhibited an AUC 0-72 /MIC smaller, but Cmax/ MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R. Conclusions and Relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount of enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.