An unusual case of ureteric stricture post robotic partial nephrectomy of a renal mass managed by Memokath insertion.

Robotic assisted partial nephrectomy is the gold standard treatment for small renal masses. Ureteric stricture is a rare but serious complication that significantly increase the morbidity and worsens the quality of life for cancer patients. Definitive treatment such as surgical reconstruction or ureteroureterostomy is not always feasible as in patients with significant morbidity or high-risk patients. Other options include ureteric double J stent or nephrostomy tube placement with regular exchange. We present a case of iatrogenic upper ureteric stricture post robotic assisted partial nephrectomy for right renal mass that was discovered on postoperative follow up imaging treated with metallic ureteral stent (Memokath) as reconstructive surgery was difficult due to proximity to the tumor bed. We found that if reconstructive surgery is not feasible, metallic ureteral stents has good durability, better quality of life than ureteric double stents for the management of ureteric stricture.

Genome-wide association study of glucocerebrosidase activity modifiers.

One of the most common genetic risk factors for Parkinson's disease (PD) are variants in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GCase deficiency has been associated with an increased PD risk, but not all individuals with low GCase activity are carriers of GBA1 mutations, suggesting other factors may be acting as modifiers. We aimed to discover common variants associated with GCase activity, as well as replicate previously reported associations, by performing a genome-wide association study using two independent cohorts: a Columbia University cohort consisting of 697 PD cases and 347 controls and the Parkinson's Progression Markers Initiative (PPMI) cohort consisting of 357 PD cases and 163 controls. As expected, GBA1 variants have the strongest association with decreased activity, led by p.N370S (beta = -4.36, se = 0.32, p = 5.05e-43). We also identify a novel association in the GAA locus (encoding for acid alpha-glucosidase, beta = -0.96, se = 0.17, p = 5.23e-09) that may be the result of an interaction between GCase and acid alpha-glucosidase based on various interaction analyses. Lastly, we show that several PD-risk loci are potentially associated with GCase activity. Further research will be needed to replicate and validate our findings and to uncover the functional connection between acid alpha-glucosidase and GCase.

Outcomes in Subfascial versus Subglandular Planes in Breast Augmentation: A Systematic Review and Meta-Analysis.

Breast augmentation is the most commonly performed aesthetic surgery procedure in women worldwide. The use of the subfascial plane has been suggested to decrease the incidence of capsular contracture compared to the subglandular plane, while simultaneously avoiding the complication of animation deformity in the subpectoral plane. The aim of this systematic review and meta-analysis was to compare the adverse outcomes of subfascial compared to subglandular planes in breast augmentation. This review was registered a priori on OSF (https://osf.io/pm92e/). A search from inception to June 2023 was performed on Medline, Embase, and CENTRAL. A hand search was also performed. All randomized and comparative cohort studies were included that assessed the use of the subfascial plane for breast augmentation. Outcomes evaluated included the incidences of seroma, hematoma, infection, rippling, capsular contracture, and revision surgery. Ten studies were included in this systematic review. Three randomized controlled trials and seven comparative cohort studies were used for quantitative synthesis. There was a significant difference favoring subfascial compared to subglandular planes in the incidence of hematoma, rippling, and capsular contracture. All included studies had high risk of bias. The current evidence suggests that the subfascial plane for breast augmentation decreases risk of capsular contracture, hematoma, and rippling compared to the subglandular plane. Further randomized evidence with high methodological rigor is still required to validate these findings.

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Previous studies have suggested that rare biallelic SYNJ1 mutations may cause autosomal recessive parkinsonism and Parkinson's disease (PD). Our study explored the impact of rare SYNJ1 variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (Pfdr=0.040). Additionally, a meta-analysis focusing on patients with EOPD demonstrated an association between all rare SYNJ1 variants and PD (Pfdr=0.029). Rare SYNJ1 variants may be associated with sporadic PD, and more specifically with EOPD.

The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank.

Coronavirus Disease 2019 (COVID-19) manifestations range from mild to severe life-threatening symptoms, including death. COVID-19 susceptibility has been associated with various factors, but studies in Qatar are limited. The objective of this study was to investigate the correlation between COVID-19 susceptibility and various sociodemographic and lifestyle factors, including age, gender, body mass index, smoking status, education level, dietary patterns, supplement usage, physical activity, a history of bariatric surgery, diabetes, and hypertension. We utilized logistic regression to analyze these associations, using the data of 10,000 adult participants, aged from 18 to 79, from Qatar Biobank. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR] = 0.55; 95% CI: 0.44-0.68 and OR = 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction in the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥ 30 kg/m2), a history of bariatric surgery, and higher adherence to the modern dietary pattern-characterized by the consumption of foods high in saturated fat and refined carbohydrates-were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Background: Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Methods: Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines and induced pluripotent stem cell-derived dopaminergic neurons and assessed lysosomal activity and the handling of aggregated synuclein fibrils. Results: We first identified specific non-coding variants in CTSB that drive the association with PD and are linked to changes in brain CTSB expression levels. Using iPSC-derived dopaminergic neurons we then find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. Moreover, in cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. Similarly, in midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition or knockout potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. Conclusions: The results of our genetic and functional studies indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

Qatar's Silent Epidemic: A Comprehensive Meta-analysis on the Prevalence of Metabolic Syndrome.

BACKGROUND: Metabolic syndrome comprises various conditions like abdominal obesity, insulin resistance, elevated triglyceride levels, reduced HDL, and high blood pressure, which pose significant health challenges globally. It's imperative to determine its prevalence in specific populations to formulate effective preventive measures. OBJECTIVE: This systematic review and meta-analysis aimed to determine the prevalence of metabolic syndrome in the Qatari population. METHODS: Using the PRISMA guidelines, a systematic search was executed on PubMed until July 2023 with keywords "Metabolic syndrome" and "Qatar." Eligibility criteria included human subjects, studies assessing metabolic syndrome components, and research conducted in Qatar or on Qatari subjects. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS). Pooled prevalence rates were calculated using the inverse variance weighting metaanalysis. RESULTS: Out of 237 studies, 14 met our inclusion criteria, with a combined sample size of 14,772 from the Qatari population. The overall pooled prevalence of metabolic syndrome was 26%. The ATP III and IDF criteria exhibited significant differences in prevalence rates, with the IDF criteria showing a higher prevalence. Age ≥ 40 years demonstrated a higher prevalence compared to the younger group. Studies post-2018 reported a decreasing trend in metabolic syndrome prevalence. CONCLUSION: The prevalence of metabolic syndrome in the Qatari population is comparable to rates in the Middle East. The study underscores the need for tailored interventions and strategies, especially targeting the older age group. Continuous research and monitoring are essential to track and understand the disease's progression in Qatar.

Development and Evaluation of a High-Fidelity Rhinoplasty Simulator.

SUMMARY: Rhinoplasty is a challenging procedure with a steep learning curve. Surgical simulators provide a safe platform to gain hands-on experience without compromising patient outcomes. Therefore, rhinoplasty is an ideal procedure to benefit from an effective surgical simulator. A high-fidelity rhinoplasty simulator was developed using three-dimensional computer modeling, three-dimensional printing, and polymer techniques. The simulator was tested by six surgeons with experience in rhinoplasty to assess realism, anatomic accuracy, and value as a training tool. The surgeons performed common rhinoplasty techniques and were provided a Likert-type questionnaire assessing the anatomic features of the simulator. A variety of surgical techniques were performed successfully using the simulator, including open and closed approaches. Bony techniques performed included endonasal osteotomies and rasping. Submucous resection with harvest of septal cartilage, cephalic trim, and tip suturing, as well as grafting techniques including alar rim, columellar strut, spreader, and shield grafts, were performed successfully. Overall, there was agreement on the simulator's anatomic accuracy of bony and soft-tissue features. There was strong agreement on the simulator's overall realism and value as a training tool. The simulator provides a high-fidelity, comprehensive training platform to learn rhinoplasty techniques to augment real operating experience without compromising patient outcomes.

Urolithiasis-related ureteric intussusception: A rare case report.

Ureteral intussusception is a rare condition that historically occurs as a complication of ureteral neoplasms or iatrogenic endoscopic procedures. Although the exact mechanism of ureteral intussusception is unclear, most reported cases are due to leading points as malignant or benign masses. Urolithiasis related is rarely reported and can be challenging in stone management as it might decrease the spontaneous stone passage rate. In addition, it will increase the complexity of the endoscopic stone management. We present the second reported case of urolithiasis-related ureteric intussusception presented with urosepsis due to obstructive uropathy, successfully managed by an endourological approach.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines and induced pluripotent stem cell-derived dopaminergic neurons and assessed lysosomal activity and the handling of aggregated synuclein fibrils. We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

A Meta Modeling-Based Interoperability and Integration Testing Platform for IoT Systems.

The rapid growth of the Internet of Things (IoT) and its integration into various industries has made it extremely challenging to guarantee IoT systems' dependability and quality, including scalability, dynamicity, and integration with existing IoT frameworks. However, the essential principles, approaches, and advantages of model-driven IoT testing indicate a promising strategy for overcoming these. This paper proposes a metamodeling-based interoperability and integration testing approach for IoT systems that automates the creation of test cases and the assessment of system performance by utilizing formal models to reflect the behavior and interactions of IoT systems. The proposed model-based testing enables the systematic verification and validation of complex IoT systems by capturing the essential characteristics of IoT devices, networks, and interactions. This study describes the key elements of model-driven IoT testing, including the development of formal models, methods for generating test cases, and the execution and assessment of models. In addition, it examines various modeling formalisms and their use in IoT testing, including state-based, event-driven, and hybrid models. This study examines several methods for creating test cases to ensure thorough and effective testing, such as constraint-based strategies and model coverage requirements. Model-driven IoT testing improves defect detection, expands test coverage, decreases testing effort, and increases system reliability. It also offers an organized and automated method to confirm the efficiency and dependability of IoT systems.

Artificial Intelligence and Machine Learning Applications in Sudden Cardiac Arrest Prediction and Management: A Comprehensive Review.

PURPOSE OF REVIEW: This literature review aims to provide a comprehensive overview of the recent advances in prediction models and the deployment of AI and ML in the prediction of cardiopulmonary resuscitation (CPR) success. The objectives are to understand the role of AI and ML in healthcare, specifically in medical diagnosis, statistics, and precision medicine, and to explore their applications in predicting and managing sudden cardiac arrest outcomes, especially in the context of prehospital emergency care. RECENT FINDINGS: The role of AI and ML in healthcare is expanding, with applications evident in medical diagnosis, statistics, and precision medicine. Deep learning is gaining prominence in radiomics and population health for disease risk prediction. There's a significant focus on the integration of AI and ML in prehospital emergency care, particularly in using ML algorithms for predicting outcomes in COVID-19 patients and enhancing the recognition of out-of-hospital cardiac arrest (OHCA). Furthermore, the combination of AI with automated external defibrillators (AEDs) shows potential in better detecting shockable rhythms during cardiac arrest incidents. AI and ML hold immense promise in revolutionizing the prediction and management of sudden cardiac arrest, hinting at improved survival rates and more efficient healthcare interventions in the future. Sudden cardiac arrest (SCA) continues to be a major global cause of death, with survival rates remaining low despite advanced first responder systems. The ongoing challenge is the prediction and prevention of SCA. However, with the rise in the adoption of AI and ML tools in clinical electrophysiology in recent times, there is optimism about addressing these challenges more effectively.

The gut microbiome in the fight against obesity: The potential of dietary factors.

Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.

Migrated Hem-o-lok clip in the bladder: A rare cause of bladder stone for cystolitholapaxy.

The bladder is the most common site of foreign bodies in the urinary tract. Most foreign bodies are self-inserted via the urethra due to exotic impulses, psychometric problems, or sexual curiosity. Here we present a rare case of bladder stones due to the migration of the Heme-o-lok clip. We present a case of a 76-year-old male with hematuria for 4 days. An abdominal computed tomography (CT) scan showed a 15 mm calculus noted in the urinary bladder. The patient underwent cystolitholapaxy which was successful. Foreign bodies inserted in the bladder pose a significant challenge and require timely intervention.

Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection.

The complement system is an essential part of innate immunity. It is activated by invading pathogens causing inflammation, opsonization, and lysis via complement anaphylatoxins, complement opsonin's and membrane attack complex (MAC), respectively. However, in SARS-CoV-2 infection overactivation of complement system is causing cytokine storm leading to multiple organs damage. In this study, the René Thomas kinetic logic approach was used for the development of biological regulatory network (BRN) to model SARS-CoV-2 mediated complement system signalling pathways. Betweenness centrality analysis in cytoscape was adopted for the selection of the most biologically plausible states in state graph. Among the model results, in strongly connected components (SCCs) pro-inflammatory cytokines (PICyts) oscillatory behaviour between recurrent generation and downregulation was found as the main feature of SARS-CoV-2 infection. Diversion of trajectories from the SCCs leading toward hyper-inflammatory response was found in agreement with in vivo studies that overactive innate immunity response caused PICyts storm during SARS-CoV-2 infection. The complex of negative regulators FI, CR1 and DAF in the inhibition of complement peptide (C5a) and PICyts was found desirable to increase immune responses. In modelling role of MAC and PICyts in lowering of SARS-CoV-2 titre was found coherent with experimental studies. Intervention in upregulation of C5a and PICyts by C3 was found helpful in back-and-forth variation of signalling pattern linked with the levels of PICyts. Moreover, intervention in upregulation of PICyts by C5a was found productive in downregulation of all activating factors in the normal SCCs. However, the computational model predictions require experimental studies to be validated by exploring the activation role of C3 and C5a which could change levels of PICyts at various phases of SARS-CoV-2 infection.

StrokeNet: An automated approach for segmentation and rupture risk prediction of intracranial aneurysm.

Intracranial Aneurysms (IA) present a complex challenge for neurosurgeons as the risks associated with surgical intervention, such as Subarachnoid Hemorrhage (SAH) mortality and morbidity, may outweigh the benefits of aneurysmal occlusion in some cases. Hence, there is a critical need for developing techniques that assist physicians in assessing the risk of aneurysm rupture to determine which aneurysms require treatment. However, a reliable IA rupture risk prediction technique is currently unavailable. To address this issue, this study proposes a novel approach for aneurysm segmentation and multidisciplinary rupture prediction using 2D Digital Subtraction Angiography (DSA) images. The proposed method involves training a fully connected convolutional neural network (CNN) to segment aneurysm regions in DSA images, followed by extracting and fusing different features using a multidisciplinary approach, including deep features, geometrical features, Fourier descriptor, and shear pressure on the aneurysm wall. The proposed method also adopts a fast correlation-based filter approach to drop highly correlated features from the set of fused features. Finally, the selected fused features are passed through a Decision Tree classifier to predict the rupture severity of the associated aneurysm into four classes: Mild, Moderate, Severe, and Critical. The proposed method is evaluated on a newly developed DSA image dataset and on public datasets to assess its generalizability. The system's performance is also evaluated on DSA images annotated by expert neurosurgeons for the rupture risk assessment of the segmented aneurysm. The proposed system outperforms existing state-of-the-art segmentation methods, achieving an 85 % accuracy against annotated DSA images for the risk assessment of aneurysmal rupture.

Association of Rare Variants in ARSA with Parkinson's Disease.

BACKGROUND: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear. OBJECTIVES: To study rare ARSA variants in PD. METHODS: To study rare ARSA variants (minor allele frequency < 0.01) in PD, we performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by a meta-analysis. RESULTS: We found evidence for associations between functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each) and in the meta-analysis (P = 0.042). We also found an association between loss-of-function variants and PD in the United Kingdom Biobank cohort (P = 0.005) and in the meta-analysis (P = 0.049). These results should be interpreted with caution as no association survived multiple comparisons correction. Additionally, we describe two families with potential co-segregation of ARSA p.E382K and PD. CONCLUSIONS: Rare functional and loss-of-function ARSA variants may be associated with PD. Further replications in large case-control/familial cohorts are required. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Aesthetic Refinements in Male Chest Lifting.

The authors describe aesthetic refinements to the approach for male chest lifting in male patients with grade 3 gynecomastia and/or significant chest skin excess. An inferior pedicle is used to transpose the nipple-areolar complex allowing preservation of pigment and sensation, liposuction and direct excision are used to reduce volume and excess skin, and the resulting curvilinear scar along the inferior and lateral border of the chest provide a more masculine appearance. Early experience with this technique has shown it to be safe and effective. Perioperative management and the detailed steps of the procedure are outlined.