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Objective: Adolescent idiopathic scoliosis (AIS) is the most prevalent spinal deformity affecting healthy children. Although AIS typically lacks symptomatic manifestations, its resultant deformities can affect patients' quality of life (QoL). Evaluating QoL and stress levels is crucial in determining the optimal brace type for AIS patients; however, research comparing the effectiveness of different brace types in this regard is lacking. Therefore, this study aimed to evaluate the impact of Boston versus Chêneau braces on QoL and stress levels in AIS patients. Methods: This cross‐sectional study was conducted at a medical institution in Riyadh, Saudi Arabia, involving 52 eligible patients selected through stratified random sampling based on type of brace as the main stratum. The inclusion criteria were idiopathic scoliosis, age ≥ 10 years, bracing for at least 3 months, and no history of cancer. QoL was evaluated according to the revised Scoliosis Research Society 22‐item questionnaire (SRS‐22r) and stress levels according to the eight‐item Bad Sobernheim stress questionnaire (BSSQ‐Brace). Independent‐sample t‐tests were used to compare brace‐related QoL and stress level according to participants' sex and brace type. Results: Overall, 32 participants were treated with Boston braces (seven men and 25 women), with a median (IQR) age of 11.00 years (10.00–13.00), and 20 participants were treated with Chêneau braces (three men, 17 women), with a median (IQR) age of 12.50 years (10.00–14.25). The total SRS‐22 score was not significantly different between the brace groups (p = 0.158). However, patients in the Boston brace group reported significantly higher satisfaction levels (median = 4.00, IQR = 3.50–4.50) than did those in the Chêneau brace group (median = 3.25, IQR = 2.38–4.13, p = 0.013, moderate effect size = 0.345, 95% CI = 0.060 to 0.590). Furthermore, the BSSQ‐brace total score was significantly higher in the Boston brace group (median = 9.00, IQR = 8.00–12.00) than in the Chêneau brace group (median = 7.50, IQR = 4.75–10.00, p = 0.007, moderate effect size = 0.376, 95% CI = 0.130 to 0.590), indicating higher stress levels in the Chêneau brace group. Conclusion: The QoL in AIS patients undergoing brace treatment was comparable across groups. Nonetheless, patients who used Chêneau braces experienced higher stress levels and lower treatment satisfaction rates than did those who used Boston braces. These findings can inform clinical decisions regarding prescription of bracing types and highlight the need for further in‐depth research. [ABSTRACT FROM AUTHOR]

The present work involved development of phospholipid‐based permeation enhancing nanovesicles (PENVs) for topical delivery of ketoprofen. Screening of phospholipids and process parameters was performed. Central composite design was used for optimization of factors, that is, amount (%, w/w) of phospholipid and ethanol at three levels. The optimized nanovesicles (NVs) were loaded with different terpenes and then incorporated into a gel base. Optimized NVs exhibited 69% entrapment efficiency, 51% transmittance, 328 nm mean vesicle size, and polydispersity index of 0.25. In vitro release kinetics evaluation indicated best fitting as per Korsemeyer–Peppa's model and drug release via Fickian‐diffusion mechanism. The optimized NVs loaded with mint terpene showed minimal degree of deformability and maximal elasticity as compared with the conventional NVs and liposomes. Rheology and texture analysis indicated pseudoplastic flow and smooth texture of the vesicle gel formulation. Ex vivo permeation studies across Wistar rat skin indicated low penetration (0.43‐fold decrease) and high skin retention (4.26‐fold increase) of ketoprofen from the optimized PENVs gel vis‐à‐vis the conventional gel. Skin irritancy study indicated lower scores for PENVs gel construing its biocompatible nature. Stability studies confirmed cold storage is best suitable for vesicle gel, and optimized PENVs were found to be suitable for topical delivery of ketoprofen. [ABSTRACT FROM AUTHOR]

Aging is a significant risk factor for the majority of prevalent human illnesses. The chance of having severe chronic conditions grows dramatically with advancing age. Indeed, more than 90% of people over 65 get at least one chronic disease, including diabetes, heart disease, malignancy, memory loss, and kidney disease, whereas more than 70% have two or more of these ailments. Mouse and human aging lead to increased senescent cells and decreased klotho concentrations. Mice lacking the protein α‐klotho show faster aging, similar to human aging. α‐Klotho upregulation extends life and slows or suppresses the onset of many age‐related illnesses and kidney diseases. Like the consequences of α‐klotho deficiency, senescent cell accumulation is linked to tissue dysfunction in various organs and multiple age‐related kidney diseases. In addition, α‐klotho and cell senescence are negatively and presumably mechanistically linked. Earlier research has demonstrated that klotho exerts its protective effects in age‐related and kidney disease by interacting with Wnt ligands, serving as an endogenous antagonist of Wnt/β‐catenin signaling. In addition, decreasing senescent cell burden with senolytics, a class of drugs that remove senescent cells selectively and extend the life span of mice. In this work, we are studying the molecular mechanism of the combination of quercetin and dasatinib as senolytic in easing age‐related chronic renal illness by altering the level of klotho/Wnt/β‐catenin. Practical applications: There is an inverse relationship between the onset and the development of age‐related disorders and cellular senescence and Klotho. Earlier attempts to suppress transforming growth factor‐beta 1 (TGF‐β1) in kidney disease with anti‐TGF‐β1 antibodies were ineffective, and this should be kept in mind. Senolytic medications may benefit from targeting senescent cells, which enhances the protective factor α‐klotho. In addition, our study provides a unique, translationally feasible route for creating orally active small compounds to enhance α‐klotho, which may also be a valuable biomarker for age‐related kidney disease. Additionally, other aspects of aging can be affected by senolytics, such as limiting age‐related mitochondrial dysfunction, lowering inflammation and fibrosis, blunting reactive oxygen species (ROS) generation, decreasing deoxyribonucleic acid (DNA) damage, and reinforcing insulin sensitivity. Senolytic agents have been shown to increase adipose progenitor and cardiac progenitor cell activity in aging animals and animals with cellular senescence‐related diseases, such as heart, brain, and kidney disease. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease due to the aging of the articular cartilage, a post‐mitotic tissue that stays functioning until primary homeostatic processes fail. Because of pain and disability, OA significantly influences national healthcare expenses and patient quality of life. It is a whole‐joint illness characterized by inflammatory and oxidative signaling pathways and significant epigenetic alterations that cause cartilage extracellular matrix degradation. The canonical Wnt pathway (Wnt/β‐catenin pathway) and nuclear factor kappa B (NF‐κB) signaling pathways may function in joint tissues by modulating the activity of synovial cells, osteoblasts, and chondrocytes. However, finding innovative ways to treat osteoarthritis and get the joint back to average balance is still a struggle. Nutraceuticals are dietary supplements that promote joint health by balancing anabolic and catabolic signals. New therapeutic methods for OA treatment have been developed based on many research findings that show nutraceuticals have strong anti‐inflammation, antioxidant, anti–bone resorption, and anabolic properties. For the treatment of osteoarthritis, we explore the possible involvement of nutraceuticals that target the Wnt/β‐catenin and NF‐κB pathways. Practical applications: In keeping with the aging population, osteoarthritis is becoming more widespread. In this extensive research, we studied the role of the Wnt/β‐catenin and NF‐κB pathway in OA formation and progression. Nutraceuticals that target these OA‐related signaling pathways are a viable therapy option. Wnt/β‐catenin and NF‐κB signaling pathway are inhibited by polyphenols, flavonoids, alkaloids, and vitamins from the nutraceutical category, making them possible therapeutic drugs for OA therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurological illness that causes memory loss over time. Currently, available pharmaceutical medicines and products are limited, and they have side effects at a higher price. Researchers and scientists have observed significant effects of nutraceuticals. Various preclinical and clinical studies were investigated for the Anti‐Alzheimer's activity of nutraceuticals. The increasing ability of the pathogenesis of AD has led to the analysis of novel therapeutic targets, including the pathophysiological mechanisms and distinct cascades. So, current improvement will show the most adequate and prominent nutraceuticals and suggested concise mechanisms involving autophagy regulation, anti‐inflammatory, antioxidant, mitochondrial homeostasis, and others. The effects of nutraceuticals cannot be ignored; it is important to investigate high‐quality clinical trials. Given the potential of nutraceuticals to battle AD as multi‐targeted therapies, it's vital to evaluate them as viable lead compounds for drug discovery and development. To the best of the authors 'knowledge, modification of blood–brain barrier permeability, bioavailability, and aspects of randomized clinical trials should be considered in prospective investigations. Practical applications: Advancements in molecular diagnostic and fundamentals have implemented particular usefulness for drug evaluation. An excess of experimental knowledge occurs regarding the effect of nutraceuticals on AD. There are various preclinical and clinical studies that have been done on nutraceuticals. In addition, various substitute inhibit and enhance some pathophysiological levels associated with AD. Nutraceuticals are easily available and have fewer side effects with cost‐effective advantages. However, further investigations and clinical trials are required to encourage its effect on disease. [ABSTRACT FROM AUTHOR]

The present research work describes development of dual drug‐loaded lipid–polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)‐functionalized LPHNPs coloaded with 5‐fluorouracil (FU) and sulforaphane (SFN) were prepared by one‐step nanoprecipitation method. Box–Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential −25.3 mV, and drug loading efficiency 19–20.3% for 5‐FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non‐Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT‐15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF‐functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF‐functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma. [ABSTRACT FROM AUTHOR]

Control of cation ordering in ABX3 perovskites is important to structural, physical and chemical properties. Here we show that thermal transformations of AA′BB′O6 double double perovskites, where both A and B sites have 1:1 cation order, to (A0.5A′0.5)2BB′O6 double perovskites with fully disordered A/A′ cations can be achieved under pressure in CaMnMnWO6 and SmMnMnTaO6, enabling both polymorphs of each material to be recovered. This leads to a dramatic switch of magnetic properties from ferrimagnetic order in double double perovskite CaMnMnWO6 to spin glass behaviour in the highly frustrated double perovskite polymorph. Comparison of double double and double perovskite polymorphs of other materials will enable effects of cation order and disorder on other properties such as ferroelectricity and conductivity to be explored. [ABSTRACT FROM AUTHOR]

Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019‐nCoV, the strain is now called as SARS‐CoV‐2. High serum levels of proinflammatory mediators, namely, interleukin‐12 (IL‐12), IL‐1β, IL‐6, interferon‐gamma (IFNγ), chemoattractant protein‐1, and IFN‐inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS‐CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D‐dimers, and procalcitonin. Supplementation of calcium during the SARS CoV‐2 associated hyperactive stage of calcium‐sensing receptors (CaSR) may be harmful to the cardio‐renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio‐renal cellular apoptosis induced by high cytokines level in COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL‐23/IL‐17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor‐α (TNF‐α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL‐17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell‐like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non‐canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways. [ABSTRACT FROM AUTHOR]

Radiation from antennas integrated with indium phosphide (InP)-based resonant tunnelling diode (RTD) oscillators is mainly through the substrate because of the effects of the large dielectric constant. Therefore, hemispherical lenses are used to extract the signal from the backside of the substrate. In this study the authors present a broadband bow-tie slot antenna with a tuning stub which is diced and mounted on a ground plane to alleviate the substrate effects. Here, the large dielectric constant substrate around the antenna conductor is removed. In addition, the ground plane underneath the diced substrate acts as a reflector and, ultimately, the antenna radiates to the air-side direction. Antenna integration with RTD oscillators is described in this study as well. Two-port bow-tie slot antennas were designed and characterised and showed the suitability of integration with power combining RTD oscillator circuits which are based on mutual coupling. The antennas were fabricated using electron beam lithography on a semi-insulating InP substrate. Simulated and measured bandwidth almost extends the entire frequency range 230-325 GHz. Simulations shows air-side radiation pattern and antenna gain of around 11 dB at 280 GHz. Simulations also show that the antenna may be fed with a 50-O or 30-O feed line, i.e. suitable feed lines, without compromising its performance which may prove beneficial for optimum loading of RTD oscillators. [ABSTRACT FROM AUTHOR]

Mobile social network (MSN), which is built upon popular smart phone devices and enables mobile users with similar interests to connect with one another, has received considerable attention in recent years. A common phenomenon that makes the MSN vivid today is mobile users often like to share attractive things to their friends in MSN. In this paper, based on this common phenomenon, we propose an efficient recommendation-based data dissemination (ReDD) protocol for MSN, which can efficiently disseminate high-quality messages in a privacy-preserving way. Specifically, in the proposed ReDD protocol, each mobile user, based on both his or her own view and his or her friends' recommendations, will form his or her personal estimation on the quality of a message. Only if the estimation of quality reaches a threshold, the message will be disseminated. In this way, high-quality messages can be widely spread in the network and occupy more network resources than low-quality ones. In order to check the validity of friends' recommendations, ReDD also employs an efficient anonymous authentication technique, which ensures that only the friends of a user can verify recommendations made by the user. Detailed security analysis demonstrates that ReDD can effectively resist various attacks launched by attackers and ensure identity privacy of nodes, confidentiality of shared keys and integrity of data packets. In addition, extensive simulations are also conducted to evaluate the performance of ReDD in terms of the number of active nodes and the average active time, and the simulation results show that high-quality messages can be disseminated widely and efficiently, while low-quality ones will be eliminated shortly to avoid occupying network resources. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetesmellitus (T2DM) share a common pathophysiology associated with similar risk factors. Genetic variants used to determine the risk of developing T2DM might also be associated with the prevalence of GDM. The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene with GDMin the Saudi female population. This is a case-control study that monitored 500 Saudi women. Subjects with GDM (n = 200) were compared with non-GDM (n = 300) controls. We opted to evaluate rs1801278 polymorphism in the IRS1 gene, which plays a critical role in the insulin-signaling pathway. Genotyping was performed with the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The frequency of the rs1801278 polymorphism was significantly higher in women with GDM than in women with non-GDM (for TT + CT versus CC: P = 0.02). Additionally, there was a significant increase in the frequency of the Arg-encoding mutant allele from GDM to non-GDM (for T versus C: P = 0.01). Our results suggest that the rs1801278 polymorphism in the IRS-1 gene is involved in the occurrence of GDM in the Saudi population. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal recessive, causing early respiratory disease and later subfertility. Whole exome sequencing may enable efficient analysis for locus heterogeneous disorders such as PCD. We whole-exome-sequenced one consanguineous Saudi Arabian with clinically diagnosed PCD and normal laterality, to attempt ab initio molecular diagnosis. We reviewed 13 known PCD genes and potentially autozygous regions (extended homozygosity) for homozygous exon deletions, non-dbSNP codon, splice-site base variants or small indels. Homozygous non-dbSNP changes were also reviewed exome-wide. One single molecular read representing RSPH9 p.Lys268del was observed, with no wild-type reads, and a notable deficiency of mapped reads at this location. Among all observations, RSPH9 was the strongest candidate for causality. Searching unmapped reads revealed seven more mutant reads. Direct assay for p.Lys268del (MboII digest) confirmed homozygosity in the affected individual, then confirmed homozygosity in three siblings with bronchiectasis. Our finding in southwest Saudi Arabia indicates that p.Lys268del, previously observed in two Bedouin families (Israel, UAE), is geographically widespread in the Arabian Peninsula. Analogous with cystic fibrosis CFTR p.Phe508del, screening for RSPH9 p.Lys268del (which lacks sentinel dextrocardia) in those at risk would help in early diagnosis, tailored clinical management, genetic counselling and primary prevention. [ABSTRACT FROM AUTHOR]

Summary Genome-wide association studies have transformed genetic studies of disease susceptibility, identifying many variants that may tag functional polymorphism nearby. Variants are often ascribed to a physically close gene exhibiting plausible functionality for a causal pathway. However, more physically remote genes may be at a lesser linkage or linkage disequilibrium (LD) distance from the tested SNP and could therefore contain the functional variant tagged. This analysis aims to identify instances where research may be misled by misassociation of a variant with a gene and develop tools to analyse genomic confounding. A catalogue of reported associations was systematically analysed for unreported genes which may represent the true functionality ascribed to a reported variant, calculating physical and genetic distances for all genes within 1 cM of the tagging polymorphism. Results revealed 55 SNPs where recombination was lower between the identified SNP and a physically more remote gene than initially reported, and 374 where an alternative gene was genetically and physically closer than the reported gene. Analyses show potential for genomic confounding through false inferences of variant association to a gene. An online visualization tool () was developed to plot genes by physical and genetic distance relative to a variant, along with LD data. [ABSTRACT FROM AUTHOR]

Identification of unknown mutations has remained laborious, expensive, and only viable for studies of selected cases. Population-based 'reference ranges' of rarer sequence diversity are not available. However, the research and diagnostic interpretation of sequence variants depends on such information. Additionally, this is the only way to determine prevalence of severe, moderate, and silent mutations and is also relevant to the development of screening programs. We previously described a system, meltMADGE, suitable for mutation scanning at the population level. Here we describe its application to a population-based study of MC4R (melanocortin 4 receptor) mutations, which are associated with obesity. We developed nine assays representing MC4R and examined a population sample of 1,100 subjects. Two 'paucimorphisms' were identified (c.307G>A/p.Val103Ile in 27 subjects and c.-178A>C in 22 subjects). Neither exhibited any anthropometric effects, whereas there would have been >90% power to detect a body mass index (BMI) effect of 0.5 kg/m2 at P=0.01. Two 'private' variants were also identified. c.335C>T/p.Thr112Met has been previously described and appears to be silent. A novel variant, c.260C>A/p.Ala87Asp, was observed in a subject with a BMI of 31.5 kg/m2 (i.e., clinically obese) but not on direct assay of a further 3,525 subjects. This mutation was predicted to be deleterious and analysis using a cyclic AMP (cAMP) responsive luciferase reporter assay showed substantial loss of function of the mutant receptor. This population-based mutation scan of MC4R suggests that there is no severe MC4R mutation with high prevalence in the United Kingdom, but that obesity-causing MC4R mutation at 1 in 1,100 might represent one of the commonest autosomal dominant disorders in man. Hum Mutat 28{3), 294-302, 2007. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Primary ciliary dyskinesia ( PCD) is an autosomal-recessive disorder characterized by impaired ciliary function that leads to subsequent clinical phenotypes such as chronic sinopulmonary disease. PCD is also a genetically heterogeneous disorder with many single gene mutations leading to similar clinical phenotypes. Here, we present a novel PCD causal gene, coiled-coil domain containing 151 ( CCDC151), which has been shown to be essential in motile cilia of many animals and other vertebrates but its effects in humans was not observed until currently. We observed a novel nonsense mutation in a homozygous state in the CCDC151 gene ( NM_145045.4:c.925 G> T:p.[ E309*]) in a clinically diagnosed PCD patient from a consanguineous family of Arabic ancestry. The variant was absent in 238 randomly selected individuals indicating that the variant is rare and likely not to be a founder mutation. Our finding also shows that given prior knowledge from model organisms, even a single whole-exome sequence can be sufficient to discover a novel causal gene. [ABSTRACT FROM AUTHOR]