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Glioma is one of the most common primary malignant brain tumors. Despite progress in therapeutic approaches, the median survival of patients with glioma remains less than 2 years, generating the need for new therapeutic approaches. Ultrasound (US) is widely used in medical fields and is used as a therapeutic tool mainly for improving the performance of therapeutic entities. In this study, we examined a novel approach using low frequency US (20 kHz) (LFUS) as an independent treatment tool for malignant glioma, since primary studies showed that cancer cells are more susceptible to LFUS than healthy cells. LFUS safety and efficacy were examined in a 9L gliosarcoma‐bearing female Fischer 344 rats. Two LFUS protocols were examined: a one‐time treatment (US1X), and two treatments 24 h apart (US2X). For safety evaluation, rats were monitored for weight change and pain measurements. For efficacy, tumor volume was measured as a function of time and the tumor structural chances were examined histopathologically. LFUS treatment showed rapid inhibition of tumor growth, seen as soon as 12 h after US application. In addition, LFUS was found to affect the tumor structure, which was more extensive (>60% of tumor area) in smaller tumors. In US2X, the tumor tissue was completely destroyed, and an extensive immune response was observed. Importantly, the treatment was highly selective, keeping the healthy tissue surrounding the tumor unharmed. We developed a highly efficient and selective therapeutic protocol for treating malignant glioma with minimal side effects based solely on LFUS.

Background Subcutaneous apomorphine is used for the treatment of Parkinson’s disease (PD); however, infusion site reactions are a common adverse event (AE), which can lead to treatment discontinuation. Apomorphine formulations that are more tolerable and convenient for use are needed. Objective Our aim was to compare the toxicity and bioavailability of ND0701, a new concentrated formulation of apomorphine free base, with one of the commercially available apomorphine HCl formulations (APO-go ® , Britannia Pharmaceuticals Ltd). Methods (1) Preclinical study: 16 minipigs were randomly assigned to placebo, APO-go ® , and ND0701 groups, and treated for 28 days. Pharmacokinetic, clinical, and pathological assessments were performed. (2) Phase I study: 18 healthy volunteers participated in an open-label, two-sequence, randomized, three single-dose, partial crossover study to compare the pharmacokinetics, safety, and tolerability of ND0701 with APO-go ® (1%). Results (1) Preclinical study: No systemic toxicity was observed in apomorphine-treated minipigs, but local skin reactions were observed at the infusion sites. These effects were less frequent and less severe and recovery was more rapid for ND0701 compared with APO-go ® . (2) Phase I study: Both formulations were safe and well tolerated under the conditions of the study and no severe or serious treatment-emergent AEs were reported. Infusion site nodules were reported more frequently, with higher severity, and recovered slower at APO-go ® -treated sites compared with ND0701-treated sites. Bioavailability of apomorphine was comparable between the two formulations. Conclusion Based on these pilot studies, ND0701 appears to be superior to APO-go ® in terms of tolerability and safety, while maintaining comparable bioavailability with APO-go ® , and shows promise as a future treatment for PD.

Background: Sarcopenia is underdiagnosed in patients with inflammatory bowel disease (IBD). Low alanine transaminase (ALT) is associated with sarcopenia. We evaluated the association between low ALT and the presence of IBD and disease activity. Methods: Data were collected from a national Israeli health insurer cohort comprising 976,615 patients. Patients with a diagnosis of IBD were compared to healthy controls. After exclusion of patients with liver disease, ALT > 40 IU/L and age < 18, a total of 233,451 patients were included in the analysis. Low ALT was defined as <10 IU/L. Results: Low ALT was more common amongst patients with IBD than in healthy controls (7.76% vs. 5.7% p < 0.001). Low ALT was found in 148 (7.9%) of the patients with CD and 69 (6.9%) of the patients with UC. For CD, low ALT was associated with increased fecal calprotectin (FC) and CRP (223.00 μg/mg [63.45–631.50] vs. 98.50 [31.98–324.00], p < 0.001, 9.10 mg/L [3.22–19.32] vs. 3.20 [1.30–8.30], p < 0.001) and decreased albumin and hemoglobin (3.90 g/dL [3.60–4.20] vs. 4.30 [4.00–4.50], p < 0.001,12.20 g/dL [11.47–13.00] vs. 13.60 [12.60–14.70], p < 0.001). For UC, low ALT was associated with higher FC and CRP (226.50 μg/mg [143.00–537.00] vs. 107.00 [40.85–499.50], p = 0.057, 4.50 mg/L [1.90–11.62] vs. 2.30 [1.00–6.20], p < 0.001) and with lower albumin and hemoglobin (4.00 g/dL [3.62–4.18] vs. 4.30 [4.10–4.40], p < 0.001, 12.40 g/dL [11.60–13.20] vs. 13.60 [12.60–14.60], p < 0.001). These findings remained consistent following multivariate regression and in a propensity score-matched cohort. Conclusions: Low ALT is more common in patients with IBD and is associated with biochemical disease activity indices.