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Background and Objectives: Peripheral nerve blockade is associated with excellent patient outcomes after surgery; however, neurologic and other complications can be devastating for the patient. This article reports the development and preliminary results of a multicenter audit describing the quality and safety of peripheral nerve blockade.Methods: From January 2006 to May 2008, patients who received peripheral nerve blockade had data relating to efficacy and complications entered into databases. All patients who received nerve blocks performed by all anesthetists during each hospital's contributing period were included. Patients were followed up by phone to detect potential neurologic complications. The timing of follow-up was either at 7 to 10 days or 6 weeks postoperatively, depending on practice location and time period. Late neurologic deficits were defined as a new onset of sensory and/or motor deficit consistent with a nerve/plexus distribution without other identifiable cause, and one of the following: electrophysiologic evidence of nerve damage, new neurologic signs, new onset of neuropathic pain in a nerve distribution area, paresthesia in relevant nerve/plexus distribution area.Results: A total of 6950 patients received 8189 peripheral nerve or plexus blocks. Of the 6950 patients, 6069 patients were successfully followed up. In these 6069 patients, there were a total of 7156 blocks forming the denominator for late neurologic complications. Thirty patients (0.5%) had clinical features requiring referral for neurologic assessment. Three of the 30 patients had a block-related nerve injury, giving an incidence of 0.4 per 1000 blocks (95% confidence interval, 0.08-1.1:1000). The incidence of systemic local anesthetic toxicity was 0.98 per 1000 blocks (95% confidence interval, 0.42-1.9:1000).Conclusions: These results indicate that the incidence of serious complications after peripheral nerve blockade is uncommon and that the origin of neurologic symptoms/signs in the postoperative period is most likely to be unrelated to nerve blockade. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Insulin resistance and β-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and β-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of β-cell cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca(2+)]i response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of β-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.

Background: In order to provide gene expression profiles of different cell types, the primary step is to isolate the specific cells of interest via laser capture microdissection (LCM), followed by extraction of good quality total RNA sufficient for quantitative real-time polymerase chain reaction (qPCR) analysis. This LCM-qPCR strategy has allowed numerous gene expression studies on specific cell populations, providing valuable insights into specific cellular changes in diseases. However, such strategy imposed challenges as cells of interests are often available in limited quantities and quality of RNA may be compromised during long periods of time spent on collection of cells and extraction of total RNA; therefore, it is crucial that protocols for sample preparation should be optimised according to different cell populations., Findings: We made several modifications to existing protocols to improve the total RNA yield and integrity for downstream qPCR analyses. A modified condensed hematoxylin and eosin (H&E) staining protocol was developed for the identification of rat renal proximal tubular cells (PTCs). It was then determined that a minimal of eight thousands renal PTCs were required to meet the minimal total RNA yield required for downstream qPCR. RNA integrity was assessed using at every progressive step of sample preparation. Therefore, we decided that the shortened H&E staining, together with microdissection should be performed consecutively within twenty minutes for good quality for gene expression analysis. These modified protocols were later applied on six individual rat samples. A panel of twenty rat renal drug transporters and five housekeeping genes showed Ct values below thirty-five, confirming the expression levels of these drug transporters can be detected., Conclusions: We had successfully optimized the protocols to achieve sufficient good quality total RNA from microdissected rat renal PTCs for gene expression profiling via qPCR. This protocol may be suitable for researchers who are interested in employing similar applications for gene expression studies.