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Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune liver disease that mostly affects women. A progressive disorder in the processes of bile secretion and enterohepatic bile salts circulation in patients with PBC already in its early stages, leading to an insufficient release of bile acids into the bowel and their entry into the systemic circulation. Insufficient bile acids released into the duodenum contributes to the development of malabsorption, energy malnutrition, and slowly progressive weight loss. The pathophysiological mechanisms of weight loss and its slow progression are associated with the deterioration of the fat emulsification processes and with the reduced absorption of hydrolyzed products, such as fatty acids and monoglycerides, with steatorrhea in patients with PBC, as well as in those with gut dysbiosis. Just in the early stages of the disease, this results in accelerated fatty acid β-oxidation that is aimed at compensating for progressive energy malnutrition. The entry of bile acids into the systemic circulation in PBC is accompanied by dyslipidemia. The mechanism of hyperlipidemia in patients with PBC differs from that in other conditions because along with an increase in total cholesterol (TC), there are elevated high-density lipoprotein levels and the appearance of unusual lipoprotein X (Lp-X). The appearance of Lp-X is most likely to be the body’s protective reaction to inactivate the detergent effect of bile acids on the membrane structures of blood corpuscles and vascular endothelial cells. It is bile acids, rather than TC levels, that correlate with the content of Lp-X and determine its formation. Concomitant hypercholesterolemia in patients with PBC is also aimed at neutralizing the detergent effect of bile acids that have entered the systemic circulation and is most likely a compensatory reaction of the body. “Anomalous” hypercholesterolemia in PBC can serve as a model system for the search and development of new methods for the treatment of dyslipidemia since it occurs without an increase in the incidence of cardiovascular events.

Background The term petrous bone cholesteatoma (PBC) refers to lesions extending deep to the bony labyrinth via superior, inferior, and posterior cell tracts. PBC is a rare incidence accounting for only 4–9% of petrous bone lesions. Lesions of petrous bone represent a real surgical challenge due to its complex relationship with critical neurovascular structures. Objective To demonstrate our 40-plus years’ experience in the management of PBC, depict the clinical features of PBC according to Sanna’s Classification, evaluate the postoperative follow-up of surgically treated PBC patients, and determine the recurrence rate. Study design Retrospective medical record review. Material and methods Medical records of 298 PBC cases operated from the year 1983 to 2024 were thoroughly evaluated. Results A total of 298 PBC cases were surgically treated at our center. The average age at presentation in this series was 47 years. Males are more affected than females with a male-to-female ratio of 2.2:1. The most common presenting symptoms were hearing loss (84%), tinnitus (48%), and facial nerve paralysis (45%). Mixed hearing loss (41%) was the commonest audiometric pattern of hearing loss followed by conductive hearing loss (26%) and profound sensorineural hearing loss (4%) and a total of 86 (29%) had anacusis at presentation. On preoperative facial nerve function examination, 133(45%) of patients had various degrees of paresis and complete paralysis whereas 55% had normal HB-I function. The commonest degree of paresis noted was HB-III (18%) followed by HB-VI (5%). A total of 150 (50%) patients had previous otologic surgery and two-thirds of these cases had two or more prior otologic surgeries. According to Sanna’s PBC Classification system, we identified that the supralabyrinthine class (44%) is the commonest of all classes followed by massive (33%), infralabyrinthine-apical (9%), infralabyrinthine(8%), and apical (5%) classes in that order. However, only ten patients had congenital type of PBC. Extension to clivus, sphenoid, nasopharynx, intradural space, and occipital condyle was found in 8, 2, 1, and 2 cases respectively. The most commonly used surgical approaches at our center were TO, MTCA with rerouting of the facial nerve, and TLAB with external auditory canal (EAC) closure. Postoperative complications were minimal and the duration of follow-up ranged from one to 458 months with a mean duration of 65 months. Residual lesions were evident in 11 cases (3.7%), with the surgical cavity, middle and posterior fossa dura, and jugular bulb being the commonest sites. Conclusion Petrous bone cholesteatoma represents diagnostically and surgically challenging lesions of temporal bone which are usually frustrating to the treating surgeon. A high index of clinical suspicion, thorough clinical evaluation examination, and preoperative radiologic evaluation make the diagnosis easier. Preoperative anatomic classification of the lesion enables the physician to choose the appropriate surgical approach. Sanna’s classification is widely used to classify PBC in relation to the labyrinthine block. Radical disease removal should always come before hearing preservation. Cavity obliteration is the solution to the problems related to a large cavity. Finally, advancements in lateral skull base approaches create adequate surgical access for the complete removal of the lesion with excellent control of critical neurovascular structures.

Background Fenofibrate (FF) has been suggested as a second-line agent in primary biliary cholangitis (PBC) patients who do not achieve adequate biochemical response to ursodeoxycholic acid (UDCA) monotherapy. Limited data exist on FF use beyond 12 months, and its long-term effects are unclear. Aim To study the biochemical outcome of long-term (>12 months) FF treatment in combination with UDCA (FF + UDCA) in PBC patients and to determine the effect on predicted prognosis using the UK-PBC Risk Score. Methods This was a retrospective cohort study of all PBC patients treated in a specialist center with FF + UDCA therapy after failure to achieve biochemical response. Liver and renal biochemical indices and the UK-PBC Risk Score at baseline and at 12, 24, 36, 48, and 60 months of FF + UDCA treatment were compared. Biochemical response was assessed using the POISE trial criteria at the end of FF + UDCA treatment. Results Data from 23 patients treated with FF + UDCA combination were analyzed. The median dose of fenofibrate was 200 mg/day, and median treatment duration was 21 months (range 1–123 months). Six (26 %) patients discontinued FF within 1 year. In patients who completed 12 months ( n  = 17) and long-term therapy, significant decrease in ALP was seen at 12 ( p  = 0.0002), 24 ( p  = 0.002), and 36 ( p  = 0.03) months. More than 75 % patients met the POISE criteria of ALP response at all study time points. There was no significant improvement in the 5-, 10-, and 15-year UK-PBC Risk Scores after FF + UDCA treatment. No significant renal impairment or adverse events were reported. Conclusion The long-term treatment of PBC patients with fenofibrate as an adjunct to UDCA is safe and effective in improving ALP, but the treatment did not significantly reduce the estimated probability of liver-related death or need for liver transplantation.

The environmental effects of fossil fuel consumption have continued to promote research in other energy sources that are more eco-friendly and can be sustained in the long run. One of the promising energy harvesting methods is plant-based energy harvesting, which has been considered a potential approach in developing energy harvesting systems for low-power applications, such as precision agriculture, environmental monitoring, and IoT sensor networks. The present research aimed to evaluate the potential of long-term energy harvesting using an Aloe vera plant, considering its health and the biocompatibility of electrodes. There was a challenge when uncoated zinc (Zn) and copper (Cu) electrodes emitted toxic ions (Zn2+ and Cu2+) that initiated foliar desiccation, tissue necrosis, and physiological degradation. Graphite-coated electrodes were henceforth brought in as biocompatible alternatives for reducing ion leakage while maintaining electrical conductivity. A commercially used wound-healing agent was also applied at sites of electrode insertion to facilitate tissue conservation. The health of the plants and energy harvesting were monitored over a period of 7 days. The results of this research have shown that material modification and application of a wound-healing agent have a positive effect on plant health without compromising energy harvesting.

There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, and chronic cholestatic diseases that can progress to liver failure. The goals of treatment are to halt the progression of liver disease to cirrhosis and/or liver failure, and alleviate symptoms associated with these diseases. Ursodeoxycholic acid has historically been the first-line treatment of PBC, with obeticholic acid and fibrates used as second-line or adjunctive therapies. However, the treatment landscape is rapidly expanding. Recently, 2 new second-line agents gained US Food and Drug Administration approval for the treatment of PBC, and several other therapies remain under investigation with promising results. Although significant progress has been made in the development of therapies for PBC, there are no current approved treatments of PSC other than liver transplantation although several emerging therapies have shown encouraging results. This review outlines the current and upcoming treatments of PBC and PSC.

This work tackles the time-varying matched external disturbances rejection problem of robust Interconnection and Damping Assignment-Passivity Based Control methodology. The main objective of this paper is the stabilization of under-actuated non-separable Port-controlled Hamiltonian (PCH) systems with an inertia matrix dependent of the unactuated coordinates, where the control input is affected by time-varying matched external disturbances. The proposed methodology adds an extension in the system coordinates, such that the system’s closed-loop stability and its PCH structure are preserved despite the presence of time-varying disturbances. The theoretical results are applied to an overhead crane and illustrated through numerical simulations.

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

Background: Managing patients with primary biliary cholangitis (PBC) who demonstrate an inadequate response to ursodeoxycholic acid or experience intolerable side effects remains a significant clinical challenge. Objectives: This study aims to investigate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in the treatment of PBC. Design: Meta-analysis and systematic review. Methods: A systematic search of publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was performed. Randomized controlled trials published in English that involved the treatment of PPAR agonists and reported on the levels of alkaline phosphatase (ALP), biochemical response rates, pruritus score, or severe and serious adverse events (AEs) were selected. The primary outcomes assessed were the effects of PPAR agonists on ALP levels and biochemical response rates. Secondary outcomes included the rates of severe or serious AEs and relief of pruritus. Results: Fourteen studies with 1137 patients were included. Compared to the control group, PPAR agonists significantly reduced ALP levels by a mean difference of −155.87 U/L (95% confidence interval (CI): −208.30 to −103.44; random-effects). Patients who received PPAR agonists showed a significantly higher biochemical response rate (risk ratio (RR), 4.42; 95% CI: 2.37–8.26; random-effects). Furthermore, there was no significant difference in the rate of severe (RR, 1.05; 95% CI, 0.49–2.28) or serious AEs (RR, 1.02; 95% CI, 0.65–1.60) between the PPAR agonists and placebo groups. Conclusion: PPAR agonists are effective and safe to treat patients with PBC. PROSPERO trial registration: CRD42024545743.

This article aimed to examine the impact of subjective norm (SN), attitude and perceived behavioural control (PBC) on Nigerian youths’ agro-entrepreneurial intention (EI) as well as moderating role of gender. The unit of analysis is 400 youths in Nigeria, ranging from ages of 18 to 40 years. In this study, structural equation modelling was used. The result shows that attitude, SN and PBC have significant relationship with Nigerian youths’ agro-EI. Also, there is no significant difference between men and women on PBC and attitude towards agro-entrepreneurship, but there is a significant difference on SN. Standard estimates revealed that women have a stronger SN than men. Finally, it was discovered that Nigerian youths have interest in agro-entrepreneurship. This study is unique since it focused specifically on agro-entrepreneurial intent and the moderating role of gender in an agrarian and gender sensitive zone, which many studies ignored. Gender role was emphasized in this study. Thus, it has shown that society and community have more influence on women than men when engaging in agro-entrepreneurship.