Liaquat University of Medical & Health Sciences

To evaluate surgical outcomes in patients with cholesteatoma-induced labyrinthine fistula, with particular emphasis on hearing preservation across different fistula stages and in selected cases requiring partial labyrinthectomy. A retrospective analysis was conducted on patients who underwent surgery for cholesteatoma with intraoperatively confirmed labyrinthine fistula at a tertiary referral center. Demographic data, clinical findings, radiological characteristics, fistula localization, size, and stage were recorded. Fistulae were classified according to the Dornhoffer–Milewski system. Surgical management was individualized according to fistula stage and intraoperative findings. Preoperative and 6-month postoperative bone-conduction (BC) thresholds were compared to assess audiological outcomes. Fistula size was measured on preoperative high-resolution computed tomography, and its relationship with postoperative hearing outcomes was analyzed. Among 230 patients operated on for cholesteatoma, 39 (17.0

Suprasellar meningiomas are classically removed through several different surgical transcranial approaches, including the pterional transsylvian route. Recently, the indications for the transsphenoidal technique, traditionally proposed only for the treatment of intrasellar lesions, have been extended to include lesions located in the supra- and parasellar areas and, among them, suprasellar meningiomas. We describe the surgical technique for the purely endoscopic endonasal transsphenoidal approach to suprasellar meningiomas. To evaluate the endoscopic endonasal technique in resection of suprasellar meningiomas and to elucidate the factors that favor this approach selection. This is a prospective study of collected data of Nineteen consecutive patients who underwent endoscopic endonasal approach (EEA) for suprasellar meningiomas (SSM) at our institution. The details of the surgical technique have been described. In this study, we analyze a series of consecutive patients who underwent endoscopic endonasal resection of SSM, evaluating both preoperative radiological parameters and intraoperative findings. We introduced new imaging predictive factors that may facilitate surgical planning and improve patient selection for EEA. Additionally, we assessed the impact of tumor size and consistency on the surgical time, extent of resection, and postoperative complications, with a particular focus on cerebrospinal fluid (CSF) leak rates and visual outcomes. Gross total removal of the lesion, without the need for brain retraction and with minimal neurovascular manipulation, was achieved in 18/19 (94.7

Arsenic in groundwater and agricultural systems poses a challenge to food safety and public health. Although environmental arsenic exposure is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), its molecular mechanism remains unclear. Chronic arsenic exposure induced hepatic steatosis and upregulated fatty acid synthase (FASN) in mice. Mechanistically, arsenic triggered splicing of X-box binding protein 1 (XBP1) into its active form, XBP1s, which promoted the transcription of glutamine-fructose-6-phosphate aminotransferase 1 (GFPT1). This increased flux of the hexosamine biosynthetic pathway (HBP) elevated UDP-GlcNAc and O-GlcNAcylation. Mass spectrometry identified Ser509 as an O-GlcNAcylated site on FASN, and its mutation abolished arsenic-induced lipid accumulation. O-GlcNAcylation at Ser509 stabilized FASN by inhibiting ubiquitin-mediated degradation and promoting fatty acid synthesis. This study identifies the XBP1s-GFPT1 axis and O-GlcNAcylation of FASN S509 as essential in arsenic-induced MASLD.

Background: Chronic neuropathic low back pain (LBP) is a prevalent health condition and difficult to treat. Conventional therapies often provide limited relief and raise safety concerns. Supplemental palmitoylethanolamide (PEA), an endogenous fatty acid amide with analgesic and anti-inflammatory properties, has shown benefits in neuropathic pain, but its application as a supportive strategy has been limited by poor oral bioavailability. Objectives: This study aimed to investigate a phospholipid-based palmitoylethanolamide formulation (PEA-PL, Cronilief™), developed using Phytosome™ delivery technology, with respect to solubility optimization, systemic exposure, and associated clinical effects in individuals with chronic neuropathic LBP. Methods: PEA-PL solubility was assessed in fasted-state simulated intestinal fluid and compared with unformulated PEA. Plasma PEA concentrations were evaluated in healthy volunteers after 2 weeks of supplementation with unformulated PEA (300 mg/day) or PEA-PL (300 or 600 mg/day). Clinical efficacy was assessed in a double-blind, placebo-controlled randomized, trial in which 120 adults with neuropathic LBP received PEA-PL 600 → 300 mg (n = 40), PEA-PL 450 mg (n = 40), or placebo (n = 40), daily for 8 weeks in addition to Standard of Care. Primary outcomes were effects on neuropathic pain (Douleur Neuropathique 4, DN4) and its intensity (Numeric Pain Rating Scale, NPRS). Secondary outcomes included effect on functional disability (Oswestry Disability Index, ODI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), quality of life (QoL) (SF-12), and concomitant analgesic use. Safety was monitored throughout the 8-week supplementation period. Results: PEA-PL increased PEA solubility approximately eight-fold and resulted in higher plasma PEA concentrations than unformulated PEA. Both PEA-PL regimens significantly improved pain, functional disability, sleep, and QoL outcomes versus placebo (all p < 0.0001), with greater effects for the 600 → 300 mg regimen. Analgesic discontinuation occurred more frequently in PEA-PL groups (65-70%). Supplementation was well tolerated. Conclusions: A phospholipid-based (Phytosome™) PEA formulation (Cronilief™) was developed and associated with optimized systemic exposure and clinically meaningful reductions in pain severity and functional disability in individuals with chronic neuropathic LBP.