Search Results (1,679)

Aerostatic bearings were proven to be an optimal choice in situations where low friction, cleanliness, and high motion accuracy are required. Their functionality relies heavily on flow restrictors, which are responsible for regulating and controlling the supply flow, and consequently, the thickness and stiffness of the fluid film. A diverse range of restrictors with varying characteristics is used, among which are the porous restrictors. The current work introduces a novel solution involving a porous, highly compressible restrictor, whose element of novelty compared to its predecessors consists of its variable thickness and corresponding permeability, regulated by the load on the bearing. The gas is supplied through an annular, elastic, deformable, porous disc, which is compressed by a metal plate, subjected to compression by the recess pressure on one side and by the supply pressure on the other side. One or more springs are used in parallel with the porous disc to obtain the optimum elastic response. The objective of this study is to evaluate the performance characteristics and compare them to a conventional restrictor. A parametric analysis is performed to define the size and properties of the porous restrictor. Full article

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), MBOAT7 (rs641738), NCAN (rs2228603), and TM6SF2 (rs58542926) SNPs with the risk of developing HCC in a Mexican population. A case-control study was conducted in unrelated Mexican individuals. Cases were 173 adults with biopsy-confirmed HCC and 346 were healthy controls. Genotyping was performed using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate associations under codominant, dominant, and recessive inheritance models. p-values were corrected using the Bonferroni test (pC). Haplotype and gene–gene interaction were also analyzed. The GG homozygous of rs738409 and rs2294918 of PNPLA3, TT, and TC genotypes of GCKR, as well as the TT genotype of MBOAT7, were associated with a significant increased risk to HCC under different inheritance models (~Two folds in all cases). The genotypes of NCAN and TM6SF2 did not show differences. The haplotype G-G of rs738409 and rs2294918 of PNPLA3 was associated with an increased risk of HCC [OR (95% CI) = 2.2 (1.7–2.9)]. There was a significant gene–gene interaction between PNPLA3 (rs738409), GCKR (rs780094), and MBOAT7 (rs641738) (Cross-validation consistency (CVC): 10/10; Testing accuracy = 0.6084). This study demonstrates for the first time that PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), and MBOAT7 (rs641738) are associated with an increased risk of developing HCC from multiple etiologies in Mexican patients. Full article

Adhesive capsulitis is a painful and progressive condition marked by significant limitations in shoulder mobility, particularly affecting external rotation. Although magnetic resonance imaging is regarded as the reference standard for assessing intra-articular structures, its high cost and limited availability present challenges in routine clinical use. In contrast, musculoskeletal ultrasound has emerged as an accessible, real-time, and cost-effective imaging modality for both the diagnosis and treatment guidance of adhesive capsulitis. This narrative review compiles and illustrates current evidence regarding the role of ultrasound, encompassing static B-mode imaging, dynamic motion analysis, contrast-enhanced techniques, and sonoelastography. Key sonographic features—such as thickening of the coracohumeral ligament, fibrosis in the axillary recess, and abnormal tendon kinematics—have been consistently associated with adhesive capsulitis and demonstrate favorable diagnostic performance. Advanced methods like contrast-enhanced ultrasound and elastography provide additional functional insights (enabling evaluation of capsular stiffness and vascular changes) which may aid in disease staging and prediction of treatment response. Despite these advantages, the clinical utility of ultrasound remains subject to operator expertise and technical variability. Limited visualization of intra-articular structures and the absence of standardized scanning protocols continue to pose challenges. Nevertheless, ongoing advances in its technology and utility standardization hold promise for the broader application of ultrasound in clinical practice. With continued research and validation, ultrasound is positioned to play an increasingly central role in the comprehensive assessment and management of adhesive capsulitis. Full article

Background: Gingival recession is a common condition involving apical displacement of the gingival margin, leading to root surface exposure and associated complications such as dentin hypersensitivity and root caries. Among the most effective treatment options are the tunneling technique (TUN) and the coronally advanced flap (CAF), both combined with connective tissue grafts (CTGs). This study aimed to evaluate and compare the clinical outcomes of TUN + CTG and CAF + CTG in terms of root coverage and keratinized tissue width (KTW) over a 6–12-month follow-up. Methods: A randomized, double-blind clinical trial was conducted following CONSORT guidelines (ClinicalTrials.gov ID: NCT06228534). Participants were randomly assigned to receive either TUN + CTG or CAF + CTG. Clinical parameters, including gingival recession depth (REC) and KTW, were assessed at baseline as well as 6 months and 12 months postoperatively using a calibrated periodontal probe. Statistical analysis was performed using descriptive statistics and linear mixed models to compare outcomes over time, with a significance level set at 5%. Results: Both techniques demonstrated significant clinical improvements. At 6 months, mean root coverage was 100% in CAF + CTG cases and 97% in TUN + CTG cases, while complete root coverage (REC = 0) was observed in 100% and 89% of cases, respectively. At 12 months, root coverage remained stable, at 99% in the CAF + CTG group and 97% in the TUN + CTG group. KTW increased in both groups, with higher values observed in the CAF + CTG group (3.53 mm vs. 3.11 mm in TUN + CTG at 12 months). No significant postoperative complications were reported. Conclusions: Both TUN + CTG and CAF + CTG are safe and effective techniques for treating RT1 and RT2 gingival recession, offering high percentages of root coverage and increased KTW. While CAF + CTG achieved slightly superior coverage and tissue gain, the TUN was associated with better aesthetic outcomes and faster recovery, making it a valuable alternative in clinical practice. Full article

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article

Gingival recession is a common problem, particularly affecting oral health and esthetics, and its treatment involves surgical root coverage procedures. The aim of this narrative review is to evaluate the role of systemic antibiotic therapy in mucogingival surgery for recession treatment. The available literature does not support routine antibiotic use in systemically healthy patients undergoing recession coverage surgery. Indications for prophylactic antibiotics are restricted to individuals at high risk of infective endocarditis and immunocompromised patients with elevated susceptibility to surgical site infections. Although mucogingival surgeries are performed in a non-sterile environment, the risk of infection remains low when proper aseptic techniques and good preoperative tissue preparation are applied. The review emphasizes the importance of making clinical decisions that consider the patient’s health status and are aligned with current recommendations. It also emphasizes the necessity for prospective studies to evaluate antibiotics’ effect on recession coverage procedures outcome. To bridge the gap between contemporary evidence and clinical practice and to foster responsible use of antibiotics in periodontal plastic surgery, the authors of this review integrate current evidence and clinical guidelines into a practical tool designed to assist clinicians in making reasoned, evidence-based decisions. Full article

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Bcakground: The deepithelialized free gingival graft (DGG) technique provides high-quality connective tissue grafts (CTGs) with predictable outcomes for recession coverage. This study evaluates a novel method of free gingival graft (FGG) deepithelialization using an Er,Cr:YSGG laser (LDEE) for treating multiple gingival recessions. Methods: A split-mouth study was conducted on 46 (n = 46) recessions in nine patients (23 per test and control group). Sites were randomized. Full-thickness palatal grafts were harvested with a scalpel. In the test group (LDEE), deepithelialization was performed extraorally using an Er,Cr:YSGG laser (2780 nm; 2.5 W, 83.3 mJ, 30 Hz, 600 µm tip). In the control group (DEE), a 15c scalpel was used. All CTGs were applied using the modified coronally advanced tunnel (TUN) technique. Clinical parameters—recession depth (RD), keratinized tissue width (KT), gingival thickness (GT), pocket depth (PD), clinical attachment loss (CAL), pink esthetic score (PES), approximal plaque index (API), mean root coverage (MRC), and complete root coverage (CRC)—were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Results: Both LDEE and DEE groups showed significant improvements in RD, KT, GT, PD, and CAL over time (p < 0.001). At T1 and T2, KT was significantly higher in the LDEE group (T1: 3.73 ± 0.72 mm; T2: 3.98 ± 0.76 mm) compared to the DEE group (T1: 3.21 ± 0.61 mm; T2: 3.44 ± 0.74 mm; p < 0.05). Other parameters (RD, GT, PD, CAL) showed no statistically significant intergroup differences at any time point (p > 0.05). After 6 months, MRC was 95% and CRC 82.6% for LDEE, compared to 94.8% and 82.6% for DEE (p > 0.05). PES scores were similar between groups at all time points (p > 0.05). Conclusions: Both laser- and scalpel-deepithelialized grafts effectively treated gingival recessions. LDEE combined with TUN resulted in significantly greater KT width compared to DEE + TUN. Full article

Pompe disease is a rare autosomal-recessive neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to the pathological accumulation of glycogen and impaired autophagy. Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) has been available since 2006, but may lead to the formation of anti-drug antibodies (ADAs) against the recombinant human enzyme, which, in turn, may adversely affect the response to ERT. Knowledge of the antigenic determinants of rhGAA involved in interaction with ADAs may facilitate the development of strategies to attenuate the anti-drug immune response in patients. Here, we determined the rhGAA ADA epitopes in the plasma of Pompe disease patients using a series of affinity purifications combined with epitope extraction and label free quantitation LC-MS. Full article

Background: Adhesive capsulitis (AC) causes a global limitation of both active and passive range of motion (ROM) in the shoulder, with or without pain, and no specific radiographic findings. Its course is self-limiting and progresses through three or four stages. The diagnosis is primarily clinical, since imaging tests are nonspecific. Treatment options include physical therapy (PT), intra-articular corticosteroid injections, suprascapular nerve block (SSNB), and hydrodilatation (HD). The latter is useful for expanding and reducing inflammation of the joint capsule through the insufflation of saline solution, anesthetics, and corticosteroids. Objectives: To compare whether patients with AC, stratified by phase 1 and 2, who receive high-volume HD as treatment achieve better outcomes in terms of shoulder pain and function compared to patients who receive low-volume HD. To compare whether there are differences in PT times and to determine mean axillary recess (AR) values. Methods: A randomized, parallel-block, triple-blind clinical trial will be conducted in 64 patients with AC in phases 1 and 2, aged 30 to 70 years, with limited active and passive ROM in two planes, and shoulder pain lasting more than 3 months. HD will be administered with volumes of 20 mL or 40 mL, followed by a conventional rehabilitation program. Outcomes will be reviewed at the 1st, 3rd, and 6th months of HD. Variables collected will include Shoulder Pain and Disability Index (SPADI), Visual Analog Scale (VAS), Range of motion (ROM), Lattinen index (LI), AR size, and time to completion of PT. Results: HD has been gaining clinical relevance in interventional rehabilitation as a treatment for AC, although its medium- and long-term efficacy remains a matter of debate. The variability in the volumes used for capsular expansion, with studies ranging from 18 mL to 47 mL, is compounded by the fact that most of these studies do not differentiate between AC stages. This could influence treatment effectiveness. Furthermore, diagnosis remains a challenge since valid and specific diagnostic parameters are lacking. Conclusions: Understanding the differences between HD techniques, considering the influence of certain factors such as the volume used or the stages of AC, as well as improving diagnosis and the coordination of scientific work. This could facilitate the development of protocols for the use of HD in AC. Full article

Background: Osteodysplastic syndromes comprise a very diverse group of clinically and genetically heterogeneous disorders characterized by defects in bone and connective tissue development, as well as in bone density. Here, we report the case of a 48-year-old female with a complex medical history characterized by bone dysplasia, hyperostosis, and partial tooth agenesis. Methods: Genetic testing was performed using WES analysis and Sanger sequencing. Molecular modeling analysis and dynamics simulation explored the impact of detected pathogenic variants. Results: The genetic analysis detected multiple pathogenic variants in genes CREB3L1, SLCO2A1, SFRP4, LRP5, and LRP6, each of which has been associated with rare osteodysplastic syndromes. The patient was homozygous for the same rare alleles associated with three of the identified autosomal recessive disorders osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type. She also had a variant linked to autosomal dominant endosteal hyperostosis and a variant previously associated with increased risk of osteoporosis and bone fractures. Two of the detected variants are predicted to cause abnormal splicing, while molecular modeling and dynamics simulations analysis suggest that the other three variants probably confer altered local secondary structure and flexibility that may have functionally devastating consequences. Conclusions: Our case highlights the rare coexistence of multiple osteodysplastic syndromes in a single patient that may complicate differential diagnosis. Furthermore, this case emphasizes the necessity for early genetic investigation of such complex cases with overlying phenotypic traits, followed by genetic counseling, facilitating orchestration of clinical interventions and allowing prevention and/or prompt management of manifestations. Full article

This paper analyzes how two major economic downturns—a recession and a stagflation—affected convergence in the European Union (EU). Absolute and conditional convergence rates are estimated using ordinary least squares (OLS) semilog regressions based on cross-sectional data from 2004 to 2022. The study tests two hypotheses: there was no absolute convergence in the EU during either the recession or the stagflation period, and conditional convergence occurred during the recession but not during stagflation. The regression results indicate that neither hypothesis can be rejected. External variables—economic openness, inflation, and investment—were more influential during stable periods, whereas internal variables—debt, unemployment, and the control of corruption—had a greater impact during crises. These findings suggest that the EU was more institutionally prepared for the stagflation due to mechanisms developed after the financial crisis, but these tools proved less effective in addressing supply-side shocks. Full article

Amyotrophic lateral sclerosis (ALS) remains a progressive neurodegenerative disease, lacking effective causal therapies. The Wobbler mouse model harboring a spontaneous autosomal recessive mutation in the vacuolar protein sorting associated protein (Vps54), has emerged as a valuable model for investigating ALS pathophysiology and potential treatments. This model exhibits cellular and phenotypic parallels to human ALS, including protein aggregation, microglia and astrocyte activation, as well as characteristic disease progression at distinct stages. Exploring the underlying pathomechanisms and identifying therapeutic targets requires a comprehensive analysis of gene and protein expression. In this study, we examined the expression of three well-established housekeeping genes and proteins—calnexin, ß-actin, and ßIII-tubulin—in the cervical spinal cord of the Wobbler model. These candidates were selected based on their demonstrated stability across various systems like animal models or cell culture. Calnexin, an integral protein of the endoplasmic reticulum, ß-actin, a structural component of the cytoskeleton, and ß-tubulin III, a component of microtubules, were quantitatively assessed using quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression and Western blotting for protein expression. Our results revealed no significant differences in the expression of CANX, ACTB, and TUBB3 between spinal cords of wild-type and Wobbler mice at the symptomatic stage (p40) at both the gene and protein levels. These findings suggest that the pathophysiological alterations induced by the Wobbler mutation do not significantly affect the expression of these crucial housekeeping genes and proteins at p40. Overall, this study provides a basis for further investigations using the Wobbler mouse model, while highlighting the potential use of calnexin, ß-actin, and ßIII-tubulin as reliable reference genes and proteins in future research to aid in the discovery for effective therapeutic interventions. Full article