Search Results (243)

Several recent studies have utilized neuroimaging to delineate the localization and function of brain regions involved in language. However, many uncertainties persist regarding the organization of the linguistic system in the human brain. The aim of the present study was to characterize the structural changes produced in a sample of 9 patients with post-stroke aphasia (4 women; mean age = 60 years, SD = 14.86) and their relationship with performance in the entire Boston Diagnostic Aphasia Examination (BDAE). Magnetic Resonance Imaging was acquired from the brain of each patient and brain lesions were assessed. Disconnection’s severity of each white matter tract by embedding the lesion into the streamline tractography atlas of the Human Connectome Project was analyzed, and grey matter lesion load using a 7-Network Cortical parcellation template was estimated, with additional subcortical, cerebellar and brainstem parcels. Finally, all data obtained was correlated with performance in the BDAE. Somatomotor network correlated with repetition scale. The disconnection of the left acoustic radiation and inferior longitudinal fasciculus correlated with repetition sub-scale. Finally, the left U-fibers correlated with severity (a BDAE sub-scale that assesses the patient’s communicative skills), conversational speech and reading sub-scales. These findings emphasized that the disconnection of these fronto-parieto-temporal structures correlate with deficits in repetition, beyond the classical hypothesis attributing such deficits solely to the impairment of the arcuate fasciculus. Full article

Polypharmacy and the use of potentially inappropriate medications (PIM) are prevalent issues among institutionalized older adults, contributing to adverse drug events and decreased quality of life. This study aimed to describe the sociodemographic and clinical characteristics associated with polypharmacy and the use of PIM in elderly people in nursing homes. A cross-sectional descriptive study was conducted among 151 residents aged ≥ 65 years. Data was extracted from institutional records. The mean age of participants was 86.48 ± 8.00 years; 71.5% were female. Excessive polypharmacy was observed in 49.7% of residents. The mean number of medications was 9.66 ± 4.18, with nervous system drugs being the most prescribed (3.73 ± 2.31). PDDIs were detected in 94% of the sample and PIMs were present in 82.8% of residents. The most common PIMs were proton pump inhibitors (ATC A) and anxiolytics (ATC N). Binary logistic regression identified two independent predictors for PIMs: the total number of medications (AOR = 1.259) and the use of ATC A (Alimentary tract and metabolism) medications (AOR = 2.315). Conversely, age and sex were not significant predictors. The study reveals a critical prevalence of excessive polypharmacy, PIM use, and PDDIs among institutionalized elderly in the Algarve. These findings underscore the urgent need for systematic, multidisciplinary medication reviews in Portuguese nursing homes to promote safer and more rational prescribing practices. Full article

Non-tuberculous mycobacteria (NTM) comprise more than 190 species capable of causing severe pulmonary, lymphatic, cutaneous, and disseminated infections, particularly in immunocompromised populations. Over the past two decades, the global incidence of NTM infections has risen steadily, underscoring an urgent unmet medical need. Treatment remains highly challenging due to intrinsic antimicrobial resistance and the requirement for prolonged multidrug regimens that are often poorly tolerated and associated with unsatisfactory outcomes. At the same time, the development of novel therapies has lagged behind other disease areas, hindered by the high costs of antimicrobial drug discovery and the relatively low commercial return compared with treatments for chronic conditions. Over the past decade, discovery and development have diversified across novel small molecules, next-generation analogues of existing classes, and adjunctive or host-directed strategies. While most candidates remain preclinical, several agents have advanced clinically in other infections, including gepotidacin (topoisomerase inhibitor; FDA-approved 2025 for urinary tract infection (UTI)), sulbactam–durlobactam (DBO β-lactamase inhibitor; FDA-approved 2023 for Acinetobacter baumannii complex), and contezolid, supporting repurposing opportunities for NTM. Conversely, SPR720 (gyrase B prodrug) was suspended after not meeting its Phase 2 endpoint in 2024, underscoring translational risk. Overall, the NTM pipeline is expanding, with near-term progress most likely from repurposed agents and optimised combinations, alongside earlier-stage candidates that target biofilms or resistance mechanisms. This review aims to provide a critical and up-to-date overview of emerging antimicrobial strategies against NTM, highlighting recent advances, translational challenges, and opportunities to accelerate the development of effective therapeutics. Full article

Introduction: Vesicoureteral reflux (VUR) is a frequent pediatric urological anomaly associated with recurrent urinary tract infections and renal scarring. Evidence on robot-assisted extravesical ureteral reimplantation (RALUR-EV) continues to grow; however, reports from Latin America remain limited. Objectives: We report an initial single-center experience with transperitoneal RALUR-EV (Lich–Gregoir) in a public pediatric hospital in Ecuador, detailing operative metrics, perioperative outcomes, and short-term radiographic efficacy using standardized definitions. Methods: A retrospective, observational study was conducted at a public tertiary referral center in Quito (January 2021–May 2025). Consecutive children (0–17 years) with VUR or ureterovesical junction (UVJ) obstruction who underwent RALUR-EV with the Lich Gregoir technique were included. The primary outcome was radiographic resolution of VUR at 3–6 months on voiding cystourethrogram. Secondary outcomes were operative times (total, console, docking), length of stay, postoperative UTI (culture-confirmed), and complications (Clavien–Dindo). Analyses were descriptive; success was reported as both evaluable-only and intention-to-treat (ITT). The study received institutional ethics approval. Results: Nine children were included (median age 4.4 years; 5 girls). Eight had VUR (5 unilateral, 3 bilateral); one had isolated UVJ obstruction. Procedures were left-sided in 7 cases and right-sided in 2. Median total operative time was 135 min (IQR 129–153); median console and docking times were 120 and 15 min, respectively. No intraoperative complications or conversions occurred. Median length of stay was 4 days (IQR 3–4). Two culture-confirmed postoperative UTIs occurred (2/9; Clavien II); no complications ≥ III were observed. Postoperative imaging was available in 6/9 cases (66.7%): radiographic resolution was 6/6 (100%) overall and 5/5 (100%) among VUR-only. ITT success was 6/9 (66.7%) overall and 5/8 (62.5%) for VUR-only. Conclusions: Transperitoneal RALUR-EV is feasible and safe in a public tertiary setting, with early effectiveness comparable to international series. Standardized pathways, structured follow-up, and multicenter collaboration are warranted to confirm durability and support broader regional adoption. Full article

Chlamydia trachomatis infection causes pelvic inflammatory disease and infertility, but how host immune factors control pathogen clearance or pathology is not fully understood. Using a mouse model of genital tract infection with Chlamydia muridarum, we examined the role of CD1d-restricted Natural killer T (NKT) cells. Invariant NKT cell-deficient mice (Jα18^−/−) showed prolonged vaginal shedding of infectious elementary bodies (EBs), delayed clearance, and decreased early cytokine production compared to wild-type (WT) controls. Conversely, CD1d^−/− mice, which lack both invariant and diverse NKT cells, did not show significant differences in vaginal shedding compared to WT mice. Surprisingly, both NKT-deficient mice (Jα18^−/− and CD1d^−/−) produced higher levels of inflammatory cytokines in the oviduct at day 35 post-infection (p.i.) and experienced more frequent upper genital tract pathology (hydrosalpinx) at day 80 p.i. However, no infectious EBs were recovered from the oviducts or uterine horns of NKT-deficient mice after day 35 p.i. Cortisone acetate reactivated infectious shedding in chronically infected NKT-deficient mice at day 100 p.i. These findings highlight distinct roles for NKT cell subsets: invariant NKT cells promote early clearance via rapid cytokine production, while the broader NKT population helps limit tissue damage. Targeting NKT pathways could help prevent chronic infection and infertility. Full article

Urinary tract infections (UTIs) are a global health concern, with over 150 million cases annually, primarily caused by Escherichia coli. Due to anatomical differences, females, especially children and postmenopausal women, are four times more susceptible. Crucially, E. coli has developed widespread antimicrobial resistance (AMR), including resistance to broad-spectrum agents and the emergence of Extended-Spectrum Beta-Lactamase (ESBL)-producing strains. This retrospective study analyzed hospital records from 95 female patients with positive urine cultures at Siblin Governmental Hospital in 2024. Patients were stratified into three age categories: children (≤18 years), adults (18–64 years) and elderly patients (>64 years). Statistical analysis using SPSS focused on descriptive resistance patterns and differences across age groups. Overall, cephalothin (85.7%) and cefaclor (78.49%) exhibited the highest resistance rates. Conversely, tigecycline (97.22%) and ertapenem (91.67%) showed the highest susceptibility. Resistance patterns varied significantly by age. For instance, elderly patients showed high resistance to agents like Augmentin (52.5%) and cefixime (66.1%), while the pediatric group (≤18 years) displayed exceptionally high resistance to cefixime (90.0%). E. coli isolates show high resistance to conventionally used antibiotics, complicating UTI treatment. These findings highlight the need for continuous local surveillance, particularly focusing on third-generation cephalosporins and beta-lactamase production. Ultimately, age is a critical factor that must be considered when determining empirical antibiotic therapy for UTIs. Full article

Gallbladder cancer (GBC), an aggressive malignancy of the biliary tract, is characterized by pronounced geographical variation and a poor prognosis, with a five-year survival rate below 20%. Despite its low global incidence, it ranks as the fifth most prevalent gastrointestinal cancer. The aim of this review is to provide a comprehensive understanding of the molecular mechanisms underpinning GBC progression, with a particular focus on the pivotal role of transcription factors (TFs) in its pathogenesis. This review delineates how aberrant regulation of TFs contributes to tumor initiation, progression, and therapeutic resistance, and to discuss the translational potential of targeting these factors for clinical benefit. Tumor suppressor TFs such as p53 and p16 frequently undergo genetic alterations, including mutations, deletions, or epigenetic silencing, leading to impaired cell cycle control, DNA repair, and apoptosis. Conversely, oncogenic TFs including TCF4, MYBL2, NF-kB, AP-1, Snail, c-MYC, SP1, FOXK1, KLF-5, STAT3 and BIRC7 are often upregulated in GBC, promoting unchecked proliferation, epithelial–mesenchymal transition (EMT), metastasis, and therapeutic resistance. This review aims to bridge current molecular insights with emerging therapeutic approaches, with particular emphasis on innovative interventions such as proteolysis-targeting chimeras (PROTACs), RNA-based therapeutics, CRISPR-driven genome editing, and epigenetic modulators, which collectively represent promising strategies for achieving more effective and personalized treatment outcomes in patients with GBC. Full article

Background and Objectives: Catheter-associated urinary tract infections (CAUTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) significantly contribute to global rates of UTI. This study aimed to compare the prevalence and trends of ESBL-producing Enterobacterales and CRE in patients with CAUTIs and non-CAUTIs. Materials and Methods: A retrospective review of 4262 UTI-positive urine cultures was conducted at King Fahad Hospital of the University, Al Khobar, Saudi Arabia (January 2022–November 2023). Demographic, clinical, and microbiological data were obtained from hospital records. Antimicrobial susceptibility was tested using the Vitek^® System; ESBL and CRE were identified using Ezy MIC™ strips and Xpert^® Carba-R assay, respectively. Results: ESBL-producing Enterobacterales accounted for 11.3% of cases; CRE comprised 1.8%. ESBL was significantly more prevalent in non-catheterized patients and those in emergency care. CRE was significantly associated with catheterized patients and inpatient settings. Escherichia coli and Klebsiella pneumoniae were the predominant ESBL-producing and CRE isolates, respectively. bla-OXA-48 was the most frequently detected carbapenemase gene (66.7%). ESBL was prevalent in younger, non-catheterized females, suggesting increasing community transmission. Conversely, CRE were primarily observed in older, catheterized inpatients, emphasizing the role of invasive devices in resistance spread. Conclusions: These findings highlight the importance of targeted infection control and early catheter removal to mitigate resistance trends. Full article

This study evaluated the effects of dietary potassium diformate supplementation on growth performance, nutrient digestibility, gastrointestinal pH, jejunal morphology, digestive enzyme activity, and antioxidant status of weaned piglets in a 28-day trial. Twenty-four weaned piglets were selected and, after a 4-day adaptation period, randomly assigned to 4 treatment groups (n = 6). The dietary treatments included a control diet (basal diet) and 3 diets supplemented with 0.6%, 1.2%, or 1.8% potassium diformate in the basal diet. The results indicated that the feed conversion ratio (FCR) of piglets was reduced by all three potassium diformate supplementation levels compared to the control group (p < 0.05). Additionally, the FCR was decreased in piglets fed the 1.8% potassium diformate-supplemented diet compared to those fed the 1.2% potassium diformate-supplemented diet (p < 0.05). Piglets fed the three potassium diformate-supplemented diets exhibited higher apparent total tract digestibility (ATTD) of dry matter and crude protein than the control group (p < 0.05). The 1.8% potassium diformate groups also showed increased ATTD of calcium and phosphorus compared to the control group (p < 0.05). Supplementation with 1.2% or 1.8% potassium diformate reduced the digesta pH in the proximal stomach, distal stomach, and duodenum, while increased jejunal villus height (VH), VH/crypt depth (VH/CD) ratio, and catalase and total superoxide dismutase activities in the jejunal mucosa compared to the control group (p < 0.05). The 1.2% potassium diformate group showed higher α-amylase activity than the control group (p < 0.05). Correlation analysis revealed that FCR negatively correlated with ATTD of dry matter, crude protein, calcium, phosphorus, and jejunal VH, while positively correlating with digesta pH in the proximal stomach (p < 0.05). The ATTD of dry matter negatively correlated with digesta pH in the proximal stomach, distal stomach, and duodenum, and positively correlated with jejunal VH/CD ratio and catalase activity (p < 0.05). The ATTD of crude protein negatively correlated with digesta pH in the proximal stomach, distal stomach, and duodenum (p < 0.05). Collectively, dietary supplementation with 1.8% potassium diformate reduced FCR of weaned piglets, which was associated with enhanced nutrient digestibility, reduced pH in the anterior gastrointestinal tract, and improved jejunal morphology. Full article

Colovesical fistulas (CVFs) are abnormal connections between the colon and bladder, most commonly associated with complicated diverticular disease. The standard treatment involves bowel resection to remove the fistulous tract and reduce the risk of recurrence. This study aimed to evaluate the feasibility and safety of laparoscopic and robotic conservative surgery for CVFs, avoiding bowel resection. Between 2012 and 2019, 12 consecutive patients underwent conservative treatment: 5 with a laparoscopic approach and 7 with a robotic approach. Perioperative outcomes showed shorter operative time and lower blood loss in the robotic group (101 min vs. 144 min, p = 0.02; 47 mL vs. 176 mL, p = 0.02). No surgical conversions were required, and the complication rate was low. One recurrence occurred in the laparoscopic group due to extensive diverticular disease. Short- and long-term outcomes demonstrated favorable functional results, with a reduced risk of complications compared to traditional bowel resection. The robotic technique provided advantages in operative time and blood loss. A conservative approach is an option for selected patients, particularly those with non-extensive diverticular disease. Full article

The gut microbiome is strongly implicated in the development of obesity and type 2 diabetes mellitus (T2DM). A recent study demonstrated that 6-week oral supplementation of Anaerostipes rhamnosivorans (ARHAM) combined with the prebiotic myo-inositol (MI) reduced fasting glucose levels in mice. In the present study, we investigated the effects of a 13-week ARHAM-MI supplementation in high-fat diet-fed mice and examined the metabolic fate of MI, including its microbial conversion into short-chain fatty acids (SCFAs), using ¹³C-MI and stable isotope tracers in the cecum, portal vein, and peripheral blood. The results showed that the ARHAM-MI group gained less weight than the MI-only and placebo groups. Analysis of intestinal mRNA and stable isotope tracing revealed that MI is primarily absorbed in the upper gastrointestinal tract, whereas microbial conversion to SCFAs predominantly occurs in the cecum and is enhanced by ARHAM. ARHAM-MI mice also showed increased cecal Gpr43 mRNA expression, indicating enhanced SCFA-mediated signaling. Notably, SCFAs derived from MI displayed distinct distribution patterns: ¹³C-butyrate was detected exclusively in the cecum, ¹³C-propionate was present in the cecum and portal vein, whereas ¹³C-acetate was the only SCFA detected in peripheral blood. Collectively, ARHAM-MI co-supplementation confers modest metabolic benefits in high-fat diet-fed mice, underscoring the need to optimize the dosage and administration frequency of ARHAM-MI to enhance its therapeutic efficacy. Full article

Background and Objectives: The optimal postoperative urinary diversion strategy after hypospadias repair remains debated, with variability in type, material, and duration. Pediatric-specific data are limited. This systematic review and meta-analysis aimed to evaluate how urinary diversion type and duration affected surgical outcomes after pediatric hypospadias repair. Materials and Methods: A systematic search of PubMed, Embase and Cochrane Library (1995–2025) databases was conducted using PRISMA guidelines and registered in PROSPERO (CRD420251121638). Eligible studies included pediatric patients undergoing hypospadias repair with or without urinary diversion. Primary endpoints were diversion characteristics (type, material, duration); secondary endpoints included postoperative complications and re-operations. Results: A total of 31 studies representing 4261 pediatric patients were analyzed, with 16 included in meta-analysis. Pooled estimates confirmed that bladder catheters were associated with significantly higher rates of general complications (wound/urinary tract infections, swelling, foreskin dehiscence) [p < 0.05] and re-operations [p < 0.05] compared to urethral stents. Conversely, urethral stents showed a greater risk of mechanical complications such as blockage and dislodgement [p = 0.001]. Meta-analysis of stented versus unstented procedures revealed no significant differences in major outcomes (fistula, stenosis, re-operations), although stented repairs showed a modest increase in minor complications. For catheterization length, pooled data suggested no significant advantage of prolonged (>5 days) versus shorter (≤5 days) diversion, despite descriptive analyses indicating more functional and general complications [p < 0.05] and re-operations [p = 0.004] after short diversion and more fistulas after prolonged diversion [p < 0.05]. Conclusions: Urinary diversion strategies significantly affected surgical outcomes after pediatric hypospadias repair. Urethral stents reduced general complications compared with bladder catheters but were prone to mechanical issues. Short diversion increased early complications, while prolonged catheterization increased fistula risk. No single approach proved universally superior; therefore, perioperative management should be individualized according to patient characteristics, hypospadias severity, and intraoperative findings. Further high-quality prospective trials are needed to define optimal diversion protocols. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men and a major cause of lower urinary tract symptoms (LUTSs). While traditional treatments such as transurethral resection of the prostate (TURP) are effective, they are associated with notable morbidity. Ultrasound-guided transperineal laser ablation (TPLA) has emerged as a minimally invasive alternative. This study aimed to assess the 12-month efficacy, safety, and functional outcomes of TPLA in patients with LUTS secondary to BPH. Methods: This was a single-center, retrospective observational cohort study including 53 patients with moderate-to-severe LUTS due to BPH who underwent TPLA between November 2021 and May 2024. Baseline and follow-up assessments were conducted at 1, 3, 6, and 12 months, including IPSS, Qmax, PVR, prostate volume (MRI), QoL, IIEF-5, and MSHQ-ED/Bother scores. The procedure was performed under local anesthesia using the EchoLaser™ system, and ablation was guided via real-time transrectal ultrasonography. Results: Statistically significant improvements were observed in IPSS (median decrease from 30 to 13), Qmax (5.5 to 13.0 mL/s), and PVR (200 to 85 mL). Prostate and adenoma volumes decreased by 41.2% and 58.3%, respectively. Quality of life scores improved, and erectile function remained stable. Ejaculatory function improved significantly based on MSHQ-ED and MSHQ-Bother scores. No major complications or conversions to surgery occurred. Conclusions: TPLA appears to be a safe, effective, and minimally invasive treatment modality for LUTS caused by BPH. It offers sustained symptomatic relief, prostate volume reduction, and preservation of sexual function, making it a promising alternative for patients unfit or unwilling to undergo invasive surgery. Full article

The lithological dichotomy in the Hammam Faraun Member (Gulf of Suez, Egypt) reveals a stable western flank with Nullipore carbonate deposits, contrasting with the clastic-prone eastern margin influenced by tectonic activity. This study aims to decipher multifactorial controls on spatial lithological variability and reservoir implications through (1) foraminiferal-based paleoenvironmental reconstruction; (2) integrated sequence stratigraphic–petrophysical analysis for sweet spot identification; and (3) synthesis of lateral facies controls. This study uniquely integrates foraminiferal paleoenvironmental proxies, sequence stratigraphy, and petrophysical analyses to understand the multifactorial controls on spatial variability and its implications for reservoir characterization. Middle Miocene sea surface temperatures, reconstructed between 19.2 and 21.2 °C, align with warm conditions favorable for carbonate production across the basin. Foraminiferal data indicate consistent bathyal depths (611–1238 m) in the eastern region, further inhibited in photic depths by clastic influx from the nearby Nubian Shield, increasing turbidity and limiting carbonate factory growth. Conversely, the western shelf, at depths of less than 100 m, supports thriving carbonate platforms. In the sequence stratigraphy analysis, we identify two primary sequences: LA.SQ1 (15.12–14.99 Ma), characterized by evaporitic Feiran Member deposits, and LA.SQ2 (14.99–14.78 Ma), dominated by clastic deposits. The primary reservoir comprises highstand systems tract (HST) sandstones with effective porosity ranging from 17% to 22% (calculated via shale-corrected neutron density cross-plots) and hydrocarbon saturation of 33%–55% (computed using Archie’s equation). These values, validated in Wells 112-58 (ϕe = 19%, S_hc = 55%) and 113M-81 (ϕe = 17%, S_hc = 33%), demonstrate the primary reservoir potential. Authigenic dolomite cement and clay content reduce permeability in argillaceous intervals, while quartz dissolution in clean sands enhances porosity. This research emphasizes that bathymetry, sediment availability, and syn-sedimentary tectonics, rather than climate, govern carbonate depletion in the eastern region, providing predictive parameters for identifying reservoir sweet spots in clastic-dominated rift basins. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly associated with gastrointestinal (GI) adverse events. This study aimed to assess the incidence and patterns of NSAID-induced GI disorders using the FDA Adverse Event Reporting System (FAERS) database and to compare the risks among different NSAIDs. Methods: NSAID-related reports were extracted from FAERS, focusing on 21 ulcer-related GI events with ≥1000 reports each, based on MedDRA v26.0. The number of reports, reporting odds ratios, and p-values were calculated and visualized using a volcano plot. Principal component analysis(PCA) was carried out to reduce the dimensionality of the dataset and revealed under-lying patterns in the data.PCA was performed to identify patterns related to risk, severity, and injury site, whereas hierarchical clustering was used to group NSAIDs based on these patterns. Hierarchical cluster analysis is a method of grouping similar data to generate a classification. Results: Statistically significant signals were identified for 19 of the 21 GI-related adverse events, including the serious condition of perforation. PCA revealed that the first component represented risk, the second severity, and the third the site of injury (upper vs. lower GI tract). Cyclooxygenase-2 (COX-2) selective NSAIDs (e.g., celecoxib, rofecoxib) were associated with a lower incidence but greater severity, primarily in the upper GI tract. Conversely, nonselective NSAIDs (e.g., acetylsalicylic acid, lornoxicam) showed higher incidence rates, though the events were generally milder. In our dataset, acetylsalicylic acid had the highest incidence, whereas meloxicam showed the highest severity. Clustering analysis revealed three distinct NSAID groups with differing patterns in risk, severity, and affected GI site. Mild adverse events may be underreported in FAERS. Dosage-related effects were not assessed in this study. Conclusions: NSAIDs differ significantly in their gastrointestinal adverse event profiles, attributable to COX selectivity. When selecting an NSAID, both the likelihood and the nature of potential GI harm should be considered. Full article