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.

GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.

The association between glucocerebrosidase, encoded by GBA, and Parkinson's disease (PD) highlights the role of the lysosome in PD pathogenesis. Genome-wide association studies in PD have revealed multiple associated loci, including the GALC locus on chromosome 14. GALC encodes the lysosomal enzyme galactosylceramidase, which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whether GALC is the gene driving the association in the chromosome 14 locus and, if so, by which mechanism. We first aimed to examine whether variants in the GALC locus and across the genome are associated with galactosylceramidase activity. We performed a genome-wide association study in two independent cohorts from (i) Columbia University; and (ii) the Parkinson's Progression Markers Initiative study, followed by a meta-analysis with a total of 976 PD patients and 478 controls with available data on galactosylceramidase activity. We further analysed the effects of common GALC variants on expression and galactosylceramidase activity using genomic colocalization methods. Mendelian randomization was used to study whether galactosylceramidase activity may be causal in PD. To study the role of rare GALC variants, we analysed sequencing data from 5028 PD patients and 5422 controls. Additionally, we studied the functional impact of GALC knockout on alpha-synuclein accumulation and on glucocerebrosidase activity in neuronal cell models and performed in silico structural analysis of common GALC variants associated with altered galactosylceramidase activity. The top hit in PD genome-wide association study in the GALC locus, rs979812, is associated with increased galactosylceramidase activity (b = 1.2; SE = 0.06; P = 5.10 × 10-95). No other variants outside the GALC locus were associated with galactosylceramidase activity. Colocalization analysis demonstrated that rs979812 was also associated with increased galactosylceramidase expression. Mendelian randomization suggested that increased galactosylceramidase activity may be causally associated with PD (b = 0.025, SE = 0.007, P = 0.0008). We did not find an association between rare GALC variants and PD. GALC knockout using CRISPR-Cas9 did not lead to alpha-synuclein accumulation, further supporting that increased rather than reduced galactosylceramidase levels may be associated with PD. The structural analysis demonstrated that the common variant p.I562T may lead to improper maturation of galactosylceramidase affecting its activity. Our results nominate GALC as the gene associated with PD in this locus and suggest that the association of variants in the GALC locus may be driven by their effect of increasing galactosylceramidase expression and activity. Whether altering galactosylceramidase activity could be considered as a therapeutic target should be further studied.

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.

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.

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.

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.

The Safe Resumption of Elective Plastic Surgery in Accredited Ambulatory Surgery Facilities During the COVID-19 Pandemic.

BACKGROUND: On March 11, 2020, the World Health Organization declared the novel Coronavirus-19 (COVID-19) a worldwide pandemic, resulting in an unprecedented shift in the Canadian healthcare system, where protection of an already overloaded system became a priority; all elective surgeries and non-essential activities were ceased. With the impact being less than predicted, on May 26, 2020, elective surgeries and non-essential activities were permitted to resume. OBJECTIVES: The authors sought to examine outcomes following elective aesthetic surgery and the impact on the Canadian healthcare system with the resumption of these services during the COVID-19 worldwide pandemic. METHODS: Data were collected in a prospective manner on consecutive patients who underwent elective plastic surgery procedures in 6 accredited ambulatory surgery facilities. Data included patient demographics, procedural characteristics, COVID-19 polymerase chain reaction (PCR) test status, airway management, and postoperative outcomes. RESULTS: A total of 368 patients underwent elective surgical procedures requiring a general anesthetic. All 368 patients who underwent surgery were negative on pre-visit screening. A COVID-19 PCR test was completed by 352 patients (95.7%) and all were negative. In the postoperative period, 7 patients (1.9%) had complications, 3 patients (0.8%) required a hospital visit, and 1 patient (0.3%) required hospital admission. No patients or healthcare providers developed COVID-19 symptoms or had a positive test for COVID-19 within 30 days of surgery. CONCLUSIONS: With appropriate screening and safety precautions, elective aesthetic plastic surgery can be performed in a manner that is safe for patients and healthcare providers and with a very low risk for accelerating virus transmission within the community.

Disease Detection in Plum Using Convolutional Neural Network under True Field Conditions.

The agriculture sector faces crop losses every year due to diseases around the globe, which adversely affect food productivity and quality. Detecting and identifying plant diseases at an early stage is still a challenge for farmers, particularly in developing countries. Widespread use of mobile computing devices and the advancements in artificial intelligence have created opportunities for developing technologies to assist farmers in plant disease detection and treatment. To this end, deep learning has been widely used for disease detection in plants with highly favorable outcomes. In this paper, we propose an efficient convolutional neural network-based disease detection framework in plum under true field conditions for resource-constrained devices. As opposed to the publicly available datasets, images used in this study were collected in the field by considering important parameters of image-capturing devices such as angle, scale, orientation, and environmental conditions. Furthermore, extensive data augmentation was used to expand the dataset and make it more challenging to enable robust training. Investigations of recent architectures revealed that transfer learning of scale-sensitive models like Inception yield results much better with such challenging datasets with extensive data augmentation. Through parameter quantization, we optimized the Inception-v3 model for deployment on resource-constrained devices. The optimized model successfully classified healthy and diseased fruits and leaves with more than 92% accuracy on mobile devices.

The Impact of Skin Care Product Sales in an Aesthetic Plastic Surgery Practice.

BACKGROUND: Despite significant growth of the global skin care market, many plastic surgeons do not offer skin care products through their aesthetic practice. However, skin care products represent a significant potential revenue stream for plastic surgeons, not only by generating revenue from product sales but by improving patient retention over time and, in turn, generating additional surgical and nonsurgical revenue. OBJECTIVES: The purpose of this study was to determine the financial implications that skin care sales can have for an aesthetic surgery practice. Our hypothesis was that patients making skin care purchases would generate higher non-skin care revenue than patients not purchasing skin care products. METHODS: A retrospective chart review was performed of all purchases made within a single aesthetic surgery practice during a 6-year period (2012-2017). Pre-tax revenue ($CAD) from each category was recorded for any patient who made a purchase during the study period. RESULTS: A total 3785 patients purchased skin care products, 5088 patients purchased nonsurgical treatments, and 3504 patients underwent surgery. Average patient spending was $720.73 (skin care), $1272.63 (nonsurgical), and $10,048.34 (surgery), respectively. Overall, patients who purchased skin care generated more revenue from the purchases of nonsurgical treatments and surgery than patients who did not purchase skin care products. CONCLUSIONS: Skin care sales not only generate revenue, but over time these patients spend more on nonsurgical and surgical treatments than patients who do not purchase skin care. Skin care is an important adjuvant to nonsurgical and surgical treatments that should be considered by all aesthetic surgeons.

Does Implant Surface Texture Affect the Risk of Capsular Contracture in Subglandular Breast Augmentation and Breast Augmentation-Mastopexy?

BACKGROUND: Previous studies have reported decreased rates of capsular contracture associated with the use of textured surface breast implants placed in the subglandular plane during breast augmentation. However, since the publication of these studies, our understanding of the pathophysiology of capsular contracture, as well as the surgical techniques utilized to minimize bacterial contamination of the implant, have advanced considerably. OBJECTIVES: The purpose of this study was to re-evaluate the relation between implant surface texturization and capsular contracture rates for breast implants placed in the subglandular plane during primary breast augmentation. METHODS: Retrospective chart review was performed of all primary subglandular breast augmentation procedures involving the use of either smooth or textured round silicone gel implants, with or without simultaneous mastopexy. The primary outcome measures included clinically significant capsular contracture (Baker grade III/IV) and revision surgery for capsular contracture. RESULTS: Between 2010 and 2017, 526 patients underwent primary subglandular breast augmentation with either smooth (n = 212) or textured (n = 314) round silicone gel implants; 248 patients underwent breast augmentation, whereas 278 underwent breast augmentation-mastopexy. Average follow-up was 756 days in the textured group and 461 days in the smooth group. Five cases of capsular contracture were observed in the textured group, and 7 cases of capsular contracture were observed in the smooth group (P = 0.20). CONCLUSIONS: Smooth surface implants placed in the subglandular plane were not at a significantly increased risk of capsular contracture compared with textured surface implants. We suggest that adherence to a surgical technique focused on minimizing bacterial contamination of the implant is of greater clinical significance than implant surface characteristics when discussing capsular contracture.

PanRV: Pangenome-reverse vaccinology approach for identifications of potential vaccine candidates in microbial pangenome.

BACKGROUND: A revolutionary diversion from classical vaccinology to reverse vaccinology approach has been observed in the last decade. The ever-increasing genomic and proteomic data has greatly facilitated the vaccine designing and development process. Reverse vaccinology is considered as a cost-effective and proficient approach to screen the entire pathogen genome. To look for broad-spectrum immunogenic targets and analysis of closely-related bacterial species, the assimilation of pangenome concept into reverse vaccinology approach is essential. The categories of species pangenome such as core, accessory, and unique genes sets can be analyzed for the identification of vaccine candidates through reverse vaccinology. RESULTS: We have designed an integrative computational pipeline term as "PanRV" that employs both the pangenome and reverse vaccinology approaches. PanRV comprises of four functional modules including i) Pangenome Estimation Module (PGM) ii) Reverse Vaccinology Module (RVM) iii) Functional Annotation Module (FAM) and iv) Antibiotic Resistance Association Module (ARM). The pipeline is tested by using genomic data from 301 genomes of Staphylococcus aureus and the results are verified by experimentally known antigenic data. CONCLUSION: The proposed pipeline has proved to be the first comprehensive automated pipeline that can precisely identify putative vaccine candidates exploiting the microbial pangenome. PanRV is a Linux based package developed in JAVA language. An executable installer is provided for ease of installation along with a user manual at https://sourceforge.net/projects/panrv2/ .

Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly.

Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs*21)]) and nonsense variant (c.2173A > T [p.(K725*)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.

Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice.

The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.

Moringa oleifera and glycemic control: A review of current evidence and possible mechanisms.

Maintaining glycemic control in diabetes and prediabetes is necessary to prevent many health complications and mortality. Although different hypoglycemic drugs are used for this purpose, there is still a growing interest in the use of medicinal plants due to their low price, easy availability, and fewer or no side effects. Moringa (Moringa oleifera Lam.) is a medicinal plant that has been traditionally used in the management of diabetes. This review aims to present the existing literature published until February 2019 on the role of moringa leaves in glycemia and their physiological mechanisms. In the conducted studies, moringa leaves have shown to reduce glycemia, without causing any adverse effects. The proposed mechanisms for reducing glycemia include inhibition of α-amylase and α-glucosidase activities, increased glucose uptake in the muscles and liver, inhibition of glucose uptake from the intestine, decreased gluconeogenesis in the liver, and increased insulin secretion and sensitivity. However, these studies are limited in numbers and mostly conducted in animals, in vitro and in vivo. Therefore, long-term human studies are required to determine the hypoglycemic effect of moringa leaves, their physiological mechanisms, active ingredients, and safety. Overall, this review provides evidence that moringa leaves have the possibility to be used as a glycemic control agent in diabetes and prediabetes.

Periareolar Augmentation-Mastopexy.

The authors describe their surgical technique for single-stage periareolar mastopexy with subglandular breast augmentation. They have performed this procedure in 85 patients since 2009 and found that this operative technique has allowed them to achieve reproducible outcomes in a single-stage procedure. Periareolar mastopexy with subglandular breast augmentation is an excellent procedure for patients who desire a larger breast size and who present with mild to moderate nipple ptosis with a paucity of excess skin in the lower pole of the breast. This article will review the perioperative management and detailed steps of the procedure and outline its indications for utilization and some of the common complications the authors have encountered.

Expanding the phenotype associated with biallelic WDR60 mutations: Siblings with retinal degeneration and polydactyly lacking other features of short rib thoracic dystrophies.

Ciliopathies are disorders of the primary cilium that can affect almost all organs and that are characterized by pleiotropy and extensive intra- and interfamilial phenotypic variability. Accordingly, mutations in the same gene can cause different ciliopathy phenotypes of varying severity. WDR60 encodes a protein thought to play a role in the primary cilium's intraflagellar transport machinery. Mutations in this gene are a rare cause of Jeune asphyxiating thoracic dystrophy (JATD) and short-rib polydactyly syndrome (SRPS). Here we report on a milder and distinct phenotype in a consanguineous Pakistani pedigree with two adolescent sisters affected by retinal degeneration and postaxial polydactyly, but lack of any further skeletal or chondrodysplasia features. By targeted high-throughput sequencing of genes known or suspected to be involved in ciliogenesis, we detected a novel homozygous N-terminal truncating WDR60 mutation (c.44delC/p.Ala15Glufs*90) that co-segregated with the disease in the family. Our finding broadens the spectrum of WDR60-related phenotypes and shows the utility of broad multigene panels during the genetic work-up of patients with ciliopathies.

Effect of Incorporating Stevia and Moringa in Cookies on Postprandial Glycemia, Appetite, Palatability, and Gastrointestinal Well-Being.

BACKGROUND: Medicinal plants including stevia and moringa constitute an important source of health-beneficial bioactive components, and hence their intake may beneficially modulate biomarkers of chronic diseases. OBJECTIVE: The objective of the present study was to investigate the effect of incorporating stevia and moringa leaf powder in cookies on postprandial glycemia, appetite, palatability, and gastrointestinal well-being in humans. METHOD: In a randomized crossover design, 20 healthy subjects consumed 3 isocaloric test foods (each providing 50 g available carbohydrates) of control cookies (CC) made from 100% wheat flour, cookies containing stevia leaf powder (SC, 3% w/w), and cookies containing moringa leaf powder (MC, 5% w/w) as breakfast. Blood glucose and subjective appetite were measured at fasting and at 15, 30, 45, 60, 90, and 120 min after the consumption of the cookies. Palatability and gastrointestinal well-being were measured using standard questionnaires. RESULTS: Compared to CC, MC resulted in a significant decrease in postprandial blood glucose concentration at 30 and 45 min (p = 0.002 and p = 0.003, respectively) and showed a tendency (p = 0.077) for lower blood glucose incremental area under the curve (iAUC). Subjects were significantly less hungry after SC and MC intake (p = 0.035 and p = 0.041, respectively) compared to CC. All the cookies were liked by the subjects without any reported gastrointestinal discomfort. CONCLUSION: The results showed that compared to CC, MC improved postprandial glycemia and reduced hunger, while SC reduced hunger only. Future studies are now warranted to explore the mechanisms responsible for these observed effects.

Visualizing the regulatory role of Angiopoietin-like protein 8 (ANGPTL8) in glucose and lipid metabolic pathways.

ANGPTL8 (Angiopoietin-like protein 8) is a newly identified hormone emerging as a novel drug target for treatment of diabetes mellitus and dyslipidemia due to its unique metabolic nature. With increasing number of studies targeting the regulation of ANGPTL8, integration of their findings becomes indispensable. This study has been conducted with the aim to collect, analyze, integrate and visualize the available knowledge in the literature about ANGPTL8 and its regulation. We utilized this knowledge to construct a regulatory pathway of ANGPTL8 which is available at WikiPathways, an open source pathways database. It allows us to visualize ANGPTL8's regulation with respect to other genes/proteins in different pathways helping us to understand the complex interplay of novel hormones/genes/proteins in metabolic disorders. To the best of our knowledge, this is the first attempt to present an integrated pathway view of ANGPTL8's regulation and its associated pathways and is important resource for future omics-based studies.