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OBJECTIVE: Studies in rodent models have suggested that reduction in renal transforming growth factor (TGF)-beta1 may underlie the renoprotective effects of the renin-angiotensin system (RAS) blockade. However, the role of the RAS blockade in abrogating TGF-beta in human disease is unknown. Accordingly, we sought to examine TGF-beta gene expression and biological activity in human renal biopsies, before and after ACE inhibition. RESEARCH DESIGN AND METHODS: RNA was extracted from renal biopsies taken from participants in the Diabiopsies study, a randomized controlled 2-year trial of 4 mg/day perindopril versus placebo that reported a reduction in proteinuria and cortical matrix expansion in type 2 diabetic nephropathy. Biopsies taken at study entry and at 2 years were obtained in 12 patients (6 placebo and 6 taking perindopril). TGF-beta1 and its receptor mRNA were quantified by real-time PCR, and its biological activity was assessed by examining the activation of its intracellular signaling pathway (phosphorylated Smad2) and the expression TGF-beta-inducible gene H3 (betaig-H3). RESULTS: At baseline, TGF-beta1 expression was similar in both placebo- and perindopril-treated groups and was unchanged over a 2-year period in biopsies of placebo-treated subjects. In contrast, perindopril treatment led to a substantial diminution in TGF-beta1 mRNA (mean 83% reduction, P < 0.05). Phosphorylated Smad2 immunolabeling and betaig-H3 mRNA were similarly reduced with ACE inhibition (P < 0.05) but unchanged in the placebo group. No differences were noted in the gene expression of TGF-beta receptor II in biopsies of either placebo- or perindopril-treated subjects. CONCLUSIONS: This study demonstrates that over a 2-year period, treatment with perindopril in patients with type 2 diabetes and nephropathy leads to a reduction in both renal TGF-beta1 gene expression and its downstream activation. [ABSTRACT FROM AUTHOR]

The article presents case studies of an 80-year-old man and a 76-year-old man who were presented with cutaneous squamous cell carcinomas and underwent surgery and adjuvant radiotherapy. Topics discussed include effectiveness of 2 Anti-Programmed Death-1 therapies in the patient with head and neck squamous cell carcinomas and magnetic resonance imaging of patients.

Acute ischemic stroke (AIS) remains a global health challenge, leading to long-term functional disabilities without timely intervention. Spatio-temporal (4D) Computed Tomography Perfusion (CTP) imaging is crucial for diagnosing and treating AIS due to its ability to rapidly assess the ischemic core and penumbra. Although traditionally used to assess acute tissue status in clinical settings, 4D CTP has also been explored in research for predicting stroke tissue outcomes. However, its potential for predicting functional outcomes, especially in combination with clinical metadata, remains unexplored. Thus, this work aims to develop and evaluate a novel multimodal deep learning model for predicting functional outcomes (specifically, 90-day modified Rankin Scale) in AIS patients by combining 4D CTP and clinical metadata. To achieve this, an intermediate fusion strategy with a cross-attention mechanism is introduced to enable a selective focus on the most relevant features and patterns from both modalities. Evaluated on a dataset comprising 70 AIS patients who underwent endovascular mechanical thrombectomy, the proposed model achieves an accuracy (ACC) of 0.77, outperforming conventional late fusion strategies (ACC = 0.73) and unimodal models based on either 4D CTP (ACC = 0.61) or clinical metadata (ACC = 0.71). The results demonstrate the superior capability of the proposed model to leverage complex inter-modal relationships, emphasizing the value of advanced multimodal fusion techniques for predicting functional stroke outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)