Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.

Trichinellosis is a parasitic zoonosis caused by a nematode parasite of the Trichinella (T.) genus. It poses significant public health issues due to limited effective and safe treatment options, especially for the muscle-encysted larval stage. Citrus paradisi (C. paradisi), with its high content of flavonoids and polyphenols, has been recorded to possess anti-parasitic properties and numerous therapeutic applications. The present work aimed to assess the efficacy of C. paradisi extract peel extract as a therapeutic agent, either alone or combined with albendazole (ABZ), against T. spiralis in experimentally infected mice. Sixty-six lab-bred Swiss albino mice were divided into control and treatment groups, then received either ABZ, C. paradisi extract, or a combination of both during the enteral, migratory, and encapsulation phases of infection. Parasitological, histopathological, and immunohistochemical examinations were performed to evaluate the efficacy of the treatments. All treated groups displayed a highly significant difference (p < 0.001) in larval counts compared to the positive control group, with the combination therapy group having the highest efficacy and the lowest mean count value during different treatment regimens. In addition, treated groups showed improved muscle integrity compared to the positive control group. Moreover, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) showed the highest expression reduction in the combination therapy group. These findings highlight the potential of C. paradisi as a complementary therapy to albendazole for treating trichinellosis through muscle larva reduction and mitigation of inflammation.

The therapeutic effects of soya consumption on adipokine concentrations have yielded inconsistent results in previous meta-analyses. This umbrella meta-analysis aims to investigate the impact of soya and its isoflavones on serum adiponectin and leptin levels in adults. We searched the Cochrane Central, Web of Science, PubMed and Scopus databases until October 10, 2024. The articles were restricted to those written in English. We included meta-analysis studies that evaluated the effects of soya and its isoflavones on levels of adiponectin and leptin and reported effect sizes (ES) and corresponding CI. Two independent reviewers screened all articles based on eligibility criteria and extracted the required data from the included meta-analyses. The meta-analysis was performed using a random-effects model in STATA software. Six meta-analyses of randomised controlled trials meeting the inclusion criteria were included in the current umbrella meta-analysis. The findings indicated that soya and its isoflavones did not have a significant effect on adiponectin (ES = 0·10; 95 % CI: −0·22, 0·41; P = 0·55; I2 = 51·8 %) and leptin (ES = −0·37; 95 % CI: −1·35, 0·61; P = 0·46; I2 = 71·2 %) concentrations. Subgroup analysis based on participants’ mean age, total sample size and duration was conducted. Results showed that the effect is not statistically significant in any of the subgroups. In conclusion, soya and its isoflavones could not improve the adipokines mentioned above. However, further high-quality research in different countries is required to substantiate these findings.

Background: Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) based cerebrovascular reactivity (CVR) indicies have enable the entirely non-invasive continuous monitoring. This study aims to compare CVR in those recovering from moderate/severe TBI to a health control group. Methods: In this prospective cohort study the cerebral oxygen CVR index, COx_a (using rSO2 and arterial blood pressure), was measured in subjects with moderate/severe TBI at follow-up. COx_a was also measured in a group of healthy controls. CVR was compared within and between these groups using conventional statistics. Results: A total of 101 heathy subject were recruited for this study along with 29 TBI patients. In the health cohort COx_a was not statistically different between males and females or in the dominate and non-dominate hemisphere. The TBI cohort, COx_a was not statistically different between first and last available follow up. Surprisingly, CVR as measured by COx_a was statistically better in those recovering from TBI than in the healthy cohort. Conclusions: In the prospective cohort study, CVR as measured by NIRS based methods, was found to be more active in those recovering from TBI than in a healthy cohort. This study may indicate that, in those that survive TBI, CVR may be enhanced as a neuroprotective measure.

Background: Inflammatory bowel disease is an autoimmune disease that affects the gut. T. spiralis larvae (E/S Ags) loaded on calcium-benzene-1,3,5-tricarboxylate metal-organic frameworks (Ca-BTC MOFs) were tested to determine whether they might prevent or cure acetic acid-induced murine colitis. Methods: T. spiralis larvae E/S Ags/Ca-BTC MOFs were used in prophylactic and therapeutic groups to either precede or follow the development of murine colitis. On the seventh day after colitis, mice were slaughtered. The effect of our target antigens on the progress of the colitis was evaluated using a variety of measures, including survival rate, disease activity index, colon weight/bodyweight, colon weight/length) ratios, and ratings for macroscopic and microscopic colon damage. The levels of inflammatory cytokines (interferon-γ and interleukin-4), oxidative stress marker malondialdehyde, and glutathione peroxidase in serum samples were evaluated. Foxp3 T-reg expression was carried out in colonic and splenic tissues. Results: T. spiralis larvae E/S Ags/Ca-BTC MOFs were the most effective in alleviating severe inflammation in murine colitis. The survival rate, disease activity index score, colon weight/length and colon weight/bodyweight ratios, and gross and microscopic colon damage scores have all considerably improved. A large decrease in proinflammatory cytokine (interferon-γ) and oxidative stress marker (malondialdehyde) expression and a significant increase in interleukin-4 and glutathione peroxidase expression were obtained. The expression of Foxp3+ Treg cells was elevated in colonic and splenic tissues. Conclusion: T. spiralis larvae E/S Ags/Ca-BTC MOFs had the highest anti-inflammatory, antioxidant, and cytoprotective capabilities against murine colitis and might be used to develop new preventative and treatment strategies.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Background: Hypothalamic hamartomas (HH) are a challenging cause of seizure in children, partly because the neural circuitry involved in ictogenesis is incompletely understood. We review our institutions’ use of magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) to treat hypothalamic hamartoma (HH) with resting-state fMRI performed immediately before and after ablation. Methods: Seed-based whole brain connectivity to thalamic regions of interest was performed immediately pre- and post- MRgLITT. Multivariable generalized linear models were used to correlate resting-state data with seizure outcomes. Results: Eight patients underwent MRgLITT treatments for HH, with a mean follow up of 29 months. Four patients (50%) were seizure free at 12 months and two (25%) had a significant improvement in seizure frequency. We identified reduced thalamocortical connectivity involving the anterior cingulate and posterior parietal regions, consistent with disconnection of the mammillothalamic tract and interruption of Papez circuit. Large-scale thalamocortical connectivity changes were driven by children who subsequently became seizure free. Conclusions: Disconnection of the mammillothalamic tract and interruption of thalamic circuitry in patients undergoing MRgLITT for HH appears to be associated with improved seizure outcomes. The ability to assess network changes immediately post- MRgLITT could enable operative adjustments to be made mid-procedure to optimize seizure outcome in real time.

We report 2 outbreaks of genetically unrelated carbapenem-resistant New Delhi metallo-β-lactamase–producing Escherichia coli caused by contaminated duodenoscopes. Using endoscopes with disposable end caps, adherence to the manufacturer’s reprocessing instructions, routine audits, and manufacturer evaluation are critical in preventing such outbreaks.

Background: While pediatric high-grade glioma (HGG) has a poor prognosis, the relationship between extent of resection (EOR), tumor location, and survival remains unclear. Our aim is to determine whether gross-total resection (GTR) is associated with prolonged survival relative to subtotal resection (STR) and biopsy. Methods: PubMed, Ovid EBM Reviews, Embase, and MEDLINE were systematically reviewed. Eligible articles were included for study-level and individual-patient data (IPD) meta-analysis. Difference by study-level and IPD characteristics were estimated using subgroup meta-analysis and meta-regression. PRISMA guidelines were followed. Results: In total, 33 studies were included. Study-level meta-analysis found GTR conferred decreased mortality relative to STR at 1 year (RR=0.73, 95%CI=0.59-0.89) and 2 years (RR=0.74, 95%CI=0.64-0.84). STR did not demonstrate survival advantages compared to biopsy at 1 year (RR=0.81, 95%CI=0.64-1.03), but showed decreased mortality at 2 years (RR=0.90, 95%CI=0.82-0.99). IPD meta-analysis comprised 186 patients, and indicated that STR (HR=2.61, 95%CI=1.56-4.38) and biopsy (HR=2.83, 95%CI=1.54-5.19) had shortened survival relative to GTR, with no differences between STR and biopsy (HR=0.93, 95%CI=0.55-1.56). In subgroup analysis, GTR was associated with prolonged survival for hemispheric tumors (HR=0.16, 95%CI=0.07-0.36) Conclusions: Among pediatric patients with HGGs, GTR was independently associated with better overall survival compared to STR and biopsy, especially in patients with hemispheric tumors.

Fertilizer nitrogen (N) management in any region following standard general recommendations discount the fact that crop response to N varies between sites and seasons. To devise field-specific N management in wheat at jointing stage (Feekes 6 growth stage) using atLeaf meter and leaf colour chart (LCC), eight field experiments were conducted in three wheat seasons during 2017–2020 in the West Delta of Egypt. In the first two seasons, four experiments consisted of treatments with a range of fertilizer N application levels from 0 to 320 kg N ha−1. Monitoring atLeaf and LCC measurements at Feekes 6 growth stage in plots with different yield potentials allowed formulation of different criteria to apply field-specific and crop need-based fertilizer N doses. In the four experiments conducted in the third season in 2019/20, different field-specific N management strategies formulated in 2017/18 and 2018/19 wheat seasons were evaluated. In the atLeaf-based fertilizer N management experiment, prescriptive application of 40 kg N ha−1 at 10 days after seeding (DAS) and 60 kg N ha−1 at 30 DAS followed by application of an adjustable dose at Feekes 6 stage computed by multiplying the difference of atLeaf measurements of the test plot and the N-sufficient plot with 42.25 (as derived from the functional model developed in this study), resulted in grain yield similar or higher to that obtained by following the standard treatment. The LCC-based strategy to apply field-specific fertilizer N at Feekes 6 stage consisted of applying 150, 100 or 0 kg N ha−1 based on LCC shade equal to or less than 4, between 4 and 5 or equal to or more than 5, respectively. Both atLeaf- and LCC-based fertilizer N management strategies not only recorded the highest grain yield levels but also resulted in higher use efficiency with 57–60 kg N ha−1 in average less fertilizer use than the standard treatment.

Epigenetic modifications have been well documented in autoimmune diseases. MicroRNAs (miRNAs), in particular, have long intrigued scientists in the field of autoimmunity. Owing to its central role in the development of the immune system, microRNA-155 (miR-155) is deeply involved in systemic lupus erythematosus (SLE). Despite the advancements made in treating SLE, the disease still remains incurable. Therefore, recent attention has been drawn to the manipulation of epigenetics in the development of curative treatments. In fact, it is a widely held view that miRNA-targeted therapy is a new glimmer of hope in the treatment of autoimmune diseases. However, the duplicity of miRNAs should not be overlooked. A single miRNA can target several mRNAs, and some mRNAs may possess opposing functions. In this review, we highlight the role of miR-155 as a biomarker and review its functions in SLE patients and animal models while discussing possible reasons behind inconsistencies across studies.

ABSTRACT IMPACT: Limited research has been conducted on the survival of men with castration-resistance prostate cancer (CRPC) with a pre-existing history of cardiovascular disease, receiving oral androgen signaling inhibitors. This study highlights all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of cardiovascular disease. OBJECTIVES/GOALS: Inadequate knowledge is known about the survival of men with castration-resistance prostate cancer (CRPC) with pre-existing history of cardiovascular disease (CVD), receiving oral androgen signaling inhibitors (OASI). We compared all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of CVD. METHODS/STUDY POPULATION: An active comparator, new user design, was used to identify 2,608 men older than age 65 years with CRPC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2011 to 2015. Patients were grouped into two analytical cohorts by CVD history. Within each analytical cohort patients were divided into two arms based on their new-user status (OASI vs. chemotherapy). All demographics and clinical characteristics were adjusted by inverse probability treatment weights (IPTWs). Unadjusted and IPTW-adjusted time-dependent Cox models, and Fine and Gray’s models were conducted to evaluate associations between OASI and all-cause and prostate cancer-specific mortality. RESULTS/ANTICIPATED RESULTS: Nearly 64.5% of patients had pre-existing CVD. We observed a lower all-cause mortality in the pre-existing CVD cohort compared to the no pre-existing CVD cohort (IPTW-adjusted hazard ratio [AHR], 0.59; 95% Confidence Interval [CI], 0.54 to 0.64; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.78, respectively). Similarly, the prostate cancer specific-mortality was showed to be lower in the pre-existing CVD cohort compared to the no pre-existing CVD cohort when comparing OASI versus chemotherapy by the IPTW-adjusted time-dependent Fine and Gray’s models (IPTW-AHR, 0.60; 95% CI, 0.55 to 0.66; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.80, respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: OASI showed a significant protective effect against all-cause and prostate cancer-specific mortality compared with chemotherapy; however, were less protective among patients without pre-existing CVD. Further studies are needed to investigate OASI in patients with and without pre-existing CVD.