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BackgroundOsteoporosis is a chronic bone metabolic disease that affects millions of people worldwide, particularly the elderly and postmenopausal women. It is characterized by weakened bones, increasing the risk of fractures and leading to significant morbidity and mortality. The goal of the current study is to examine the reported osteo-preservative effects of exercise and/or fasting in the Ramadan fasting model (RFM) in ovariectomized (OVX) rats.MethodsThe experimental intervention started 1 month following the ovariectomy procedure and consisted of five 15-min exercise sessions per week at 18–25 m/min and/or an approximately 13-h fast from sunrise to sunset (6:00 AM–19:00 PM). Serum bone metabolism biomarker levels were measured, and mineral concentrations in femoral ashed bones and digested serum were determined. Additionally, serum bone alkaline phosphatase (b-ALP), parathyroid hormone, osteocalcin, calcitonin, and vitamin D3 concentrations were measured using the competitive enzyme immunoassay technique.ResultsCalcium, magnesium, and phosphorus showed a notable decrease in mineral concentration among OVX rat femurs compared with the combination group (OVX + RFM + E) and control groups. In addition, homeostasis of serum concentrations of calcium, magnesium, and phosphorus was observed to increase in the OVX + RFM + E group rather than in the OVX group without intervention when compared with a control group. Furthermore, fasting and exercise, either alone or concurrently with ovariectomy, induced a non-significant elevation in osteocalcin, parathyroid hormone, and vitamin D3, whereas b-ALP and calcitonin increased significantly compared with those in control rats.ConclusionThe combination of the Ramadan fasting model and moderate intensity exercises among OVX rats manifested advantageous effects in bone biomarkers compared with OVX rats without intervention. This could be recommended as a lifestyle modification that is protective against osteoporosis, especially in the context of depleted estrogen hormone after menopause.

Abstract Helminth-derived proteins have immunomodulatory properties, influencing the host’s immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn’s disease.

Abstract Background Long-read whole genome sequencing (lrWGS) has the potential to address the technical limitations of exome sequencing in ways not possible by short-read WGS. However, its utility in autosomal recessive Mendelian diseases is largely unknown. Methods In a cohort of 34 families in which the suspected autosomal recessive diseases remained undiagnosed by exome sequencing, lrWGS was performed on the Pacific Bioscience Sequel IIe platform. Results Likely causal variants were identified in 13 (38%) of the cohort. These include (1) a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis, (2) a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder, (3) a compound heterozygous SV in RP1L1 with complex inheritance pattern in a family with inherited retinal disease, (4) homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families, and (5) a promoter SNV in SLC4A4 causing non-syndromic band keratopathy. Surprisingly, we also encountered causal variants that could have been identified by short-read exome sequencing in 7 families. The latter highlight scenarios that are especially challenging at the interpretation level. Conclusions Our data highlight the continued need to address the interpretation challenges in parallel with efforts to improve the sequencing technology itself. We propose a path forward for the implementation of lrWGS sequencing in the setting of autosomal recessive diseases in a way that maximizes its utility.

Abstract Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance). Overall, we estimate a probability of 34.3% for encountering at least one of these challenges. Importantly, our data show that by only addressing non-sequencing-based challenges, around 71% increase in the diagnostic yield can be expected. Indeed, by applying these lessons to a cohort of 314 cases with negative clinical exome or genome reports, we could identify the likely causal variant in 54.5%. Our work highlights the need to have a thorough approach to undiagnosed diseases by considering a wide range of challenges rather than a narrow focus on sequencing technologies. It is hoped that by sharing this experience, the yield of undiagnosed disease programs globally can be improved.

BackgroundAdaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood.MethodsTonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs.ResultsStrong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies.ConclusionOur results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.

Abstract The convection, thermal conductivity, and heat transfer of hybrid nanofluid through nanoparticles has become integral part of several natural and industrial processes. In this manuscript, a new fractionalized model based on hybrid nanofluid is proposed and investigated by employing singular verses and non-singular kernels. The mathematical modeling of hybrid nanofluid is handled via modern fractional definitions of differentiations. The combined Laplace and Fourier Sine transforms have been configurated on the governing equations of hybrid nanofluid. The analytical expression of the governing temperature and velocity equations of hybrid nanofluid have been solved via special functions. For the sake of thermal performance, dimensional analysis of governing equations and suitable boundary conditions based on Mittage-Leffler function have been invoked for the first time in literature. The comparative analysis of heat transfer from hybrid nanofluid has been observed through Caputo-Fabrizio and Atangana-Baleanu differential operators. Finally, our results suggest that volume fraction has the decelerated and accelerated trends of temperature distribution and inclined and declined profile of heat transfer is observed copper and alumina nanoparticles.

Misdiagnosing suspected COVID-19 individuals could largely contribute to the viruses transmission, therefore, making an accurate diagnosis of infected subjects vital in minimizing and containing the disease. Although RT-PCR is the standard method in detecting COVID-19, it is associated with some limitations, including possible false negative results. Therefore, serological testing has been suggested as a complement assay to RT-PCR to support the diagnosis of acute infections. In this study, 15 out of 639 unvaccinated healthcare workers (HCWs) were tested negative for COVID-19 by RT-PCR and were found seropositive for SARS-CoV-2 nucleocapsid protein-specific IgM and IgG antibodies. These participants underwent additional confirmatory RT-PCR and SARS-CoV-2 spike-specific ELISA tests. Of the 15 individuals, nine participants were found negative by second RT-PCR but seropositive for anti-spike IgM and IgG antibodies and neutralizing antibodies confirming their acute infection. At the time of collection, these nine individuals were in close contact with COVID-19-confirmed patients, with 77.7% reporting COVID-19-related symptoms. These results indicate that including serological tests in the current testing profile can provide better outcomes and help contain the spread of the virus by increasing diagnostic accuracy to prevent future outbreaks rapidly.

A collection of metabolic disorders and neurodegenerative diseases linked to oxidative stress and neuroinflammation frequently affect postmenopausal women or estrogen deprivation. Recent research has focused on alternative therapies that can enhance these women’s quality of life. This study set out to investigate the effects of physical exercise (EX) and intermittent fasting (IF) on oxidants/antioxidants, inflammatory cytokines, neurotransmitters, and brain-derived neurotrophic factor (BDNF) in the cortex of rats. Additionally, it sought to assess the response to oxidative stress and neuroinflammation in the brains of rats following ovariectomy (OVX) and the potential mechanisms of these interventions. Fifty female rats were divided into one of the following groups 30 days after bilateral OVX: Control, OVX, OVX + EX, OVX + IF, and OVX + EX + IF groups. The rats in the Control and OVX groups continued their normal activities and had unrestricted access to food and water, but the rats in the OVX + EX and OVX + EX + IF groups had a 4-week treadmill training program, and the rats in the OXV + IF and OVX + EX + IF groups fasted for 13 h each day. The rats were killed, the cerebral cortex was taken, tissue homogenates were created, and various parameters were estimated using these homogenates. The results show that ovariectomized rats had decreased levels of neurotransmitters (DA, NE, and SE), acetylcholinesterase, brain GSH (glutathione), SOD (superoxide dismutase), catalase, GPx (glutathione peroxidase), and TAC (total antioxidant capacity), as well as elevated levels of proinflammatory cytokines and mediators (TNF-α, IL-1β, Cox-2). While ovariectomy-induced declines in neurotransmitters, enzymatic and nonenzymatic molecules, neuroinflammation, and oxidative brain damage were considerably mitigated and prevented by treadmill exercise and intermittent fasting, BDNF was significantly increased. These results suggest that ovariectomy can impair rat neuronal function and regular treadmill exercise and intermittent fasting seem to protect against ovariectomy-induced neuronal impairment through the inhibition of oxidative stress and neuroinflammation and increased BDNF levels in the brain cortex. However, combining regular exercise and intermittent fasting did not provide additional benefits compared to either treatment alone.

Abstract SLC25A42 is the main transporter of coenzyme A (CoA) into mitochondria. To date, 15 individuals have been reported to have one of two bi‐allelic homozygous missense variants in the SLC25A42 as the cause of mitochondrial encephalomyopathy, of which 14 of them were of Saudi origin and share the same founder variant, c.871A > G:p.Asn291Asp. The other subject was of German origin with a variant at canonical splice site, c.380 + 2 T > A. Here, we describe the clinical manifestations and the disease course in additional six Saudi patients from four unrelated consanguineous families. While five patients have the Saudi founder p.Asn291Asp variant, one subject has a novel deletion. Functional analyses on fibroblasts obtained from this patient revealed that the deletion causes significant decrease in mitochondrial oxygen consumption and ATP production compared to healthy individuals. Moreover, extracellular acidification rate revealed significantly reduced glycolysis, glycolytic capacity, and glycolytic reserve as compared to control individuals. There were no changes in the mitochondrial DNA (mtDNA) content of patient fibroblasts. Immunoblotting experiments revealed significantly diminished protein expression due to the deletion. In conclusion, we report additional patients with SLC25A42‐associated mitochondrial encephalomyopathy. Our study expands the molecular spectrum of this condition and provides further evidence of mitochondrial dysfunction as a central cause of pathology. We therefore propose that this disorder should be included in the differential diagnosis of any patient with an unexplained motor and speech delay, recurrent encephalopathy with metabolic acidosis, intermittent or persistent dystonia, lactic acidosis, basal ganglia lesions and, especially, of Arab ethnicity. Finally, deep brain stimulation should be considered in the management of patients with life altering dystonia.

Abstract Background Dendritic cells (DCs) play a key role in shaping T cell responses. To do this, DCs must be able to migrate to the site of the infection and the lymph nodes to prime T cells and initiate the appropriate immune response. Integrins such as β2 integrin play a key role in leukocyte adhesion, migration, and cell activation. However, the role of β2 integrin in DC migration and function in the context of infection-induced inflammation in the gut is not well understood. This study looked at the role of β2 integrin in DC migration and function during infection with the nematode worm Trichuris muris. Itgb2tm1Bay mice lacking functional β2 integrin and WT littermate controls were infected with T. muris and the response to infection and kinetics of the DC response was assessed. Results In infection, the lack of functional β2 integrin significantly reduced DC migration to the site of infection but not the lymph nodes. The lack of functional β2 integrin did not negatively impact T cell activation in response to T. muris infection. Conclusions This data suggests that β2 integrins are important in DC recruitment to the infection site potentially impacting the initiation of innate immunity but is dispensible for DC migration to lymph nodes and T cell priming in the context of T. muris infection.

The Arabic language has many spoken dialects. However, until recently, it was primarily written in Modern Standard Arabic (MSA), which is the formal variant of Arabic. Social media platforms have changed the face of written Arabic where users converse freely in various dialects, thus offering a massive number of resources for the study of dialectal text. The Arabic dialects differ from MSA in morphology, syntax, and phonetics. Consequently, since the effectiveness of NLP tasks—like sentiment analysis—is dependent on the availability of representative resources, there is currently a great need for such resources in these dialects. In this paper, we present MARSA—the largest sentiment annotated corpus for Dialectal Arabic (DA) in the Gulf region, which consists of 61,353 manually labeled tweets that contain a total of 840 K tokens. The tweets were collected from trending hashtags in four domains: political, social, sports, and technology to create a multi-domain corpus. The importance of such a corpus is to facilitate the study of domain-dependent sentiment analysis in Arabic. In addition to this corpus, the annotators extracted indicator words to form affect lexicons for each domain. We draw insights from these lexicons regarding contextual polarity of certain words. Furthermore, we present benchmark experiments on the MARSA corpus in order to establish a baseline for further studies.

The study aimed to determine the prevalence of different species of Vibrio spp. in fish and shellfish sold in subtropical-arid countries (United Arab Emirates). It also examined the antimicrobial resistance of the isolated species and their growth behavior upon in vitro environmental changes concerning temperature, pH, and salinity. The prevalence of Vibrio spp. in fish and shellfish samples, was 64.5 and 92%, respectively. However, Vibrio parahemolyticus were detected in a mere 7.5 and 13.0% of the samples, respectively. On the other hand, Vibrio mimicus was detected in 1.5 and 8.5% of the samples, respectively. None of the six antibiotics studied except for Sulfamethoxazole-trimethoprim were effective against fish Vibrio spp. isolates. On a similar note, three antibiotics, namely Penicillin, Daptomycin, and Vancomycin, were ineffective against the shellfish isolates. The growth of the microorganisms did not show any significant trend with changes in pH and salinity. The optimum temperature for Vibrio spp. growth was observed to be 37°C.

Abstract Background At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce. Results Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the entire cohort and find that TDVs account for 15% of all “solved” cases. We compare the results of RT-PCR to in silico prediction. Definitive results from RT-PCR are obtained from blood-derived RNA for the overwhelming majority of variants (84.1%), and only a small minority (2.6%) fail analysis on all available RNA sources (blood-, skin fibroblast-, and urine renal epithelial cells-derived), which has important implications for the clinical application of RNA-seq. We also show that RNA analysis can establish the diagnosis in 13.5% of 155 patients who had received “negative” clinical WES reports. Finally, our data suggest a role for TDVs in modulating penetrance even in otherwise highly penetrant Mendelian disorders. Conclusions Our results provide much needed empirical data for the impending implementation of diagnostic RNA-seq in conjunction with genome sequencing.

Obesity is a global epidemic disease that is closely associated with various health problems as Diabetes mellitus, cardiovascular, and metabolic disorders. Lycopene (LYC), a red-colored carotenoid, has demonstrated various promising therapeutic effects. Hence, the potential of LYC was studied against high fat diet (HFD)-induced obesity and metabolic disturbances in rats. Animals fed on HFD and orally supplemented with LYC (25 and 50 mg/kg) or simvastatin (10 mg/kg) every day for 3 months. The results revealed that long-term consumption of HFD significantly increased weight gain, liver weight, cholesterol, triglycerides (TG), apolipoprotein-B (Apo-B), low-density lipoprotein-cholesterol (LDL-c) levels, as well as decreasing the high-density lipoprotein-cholesterol (HDL-c) levels. Moreover, high blood glucose and insulin levels accompanied by low peroxisome proliferator activated receptor gamma (PPAR-γ) were recorded in HFD group. Further, HFD rats displayed lower levels of antioxidant biomarkers (SOD, CAT, GPx, GR and GSH), in addition to higher levels of MDA, NO and inflammatory mediators (IL-1β, TNF-α, and MPO). Marked increases were observed in atherogenic index, lactate dehydrogenase and creatine kinase together with fibrosis markers (TGF-β1 and α-SMA) in rats fed on HFD. Comparing to model group, LYC was able to effectively reverse HFD-mediated alterations at dose dependent manner. Altogether, dietary supplementation of LYC successfully reversed HFD-induced alterations through its antioxidant, anti-inflammatory, and anti-fibrotic properties. Hence, LYC displayed a therapeutic potential to manage obesity and its associated pathologies.

The complicated disorder of hypercholesterolemia has several underlying factors, including genetic and lifestyle factors. Low LDL cholesterol and elevated serum total cholesterol are its defining features. A carotenoid with antioxidant quality is lycopene. Examining lycopene activity in an animal model of hypercholesterolemia induced using food was the aim of this investigation. Triglycerides, LDL cholesterol, HDL cholesterol, and plasma total cholesterol were all measured. Biomarkers of renal and cardiac function were also examined. Apoptotic indicators, pro-inflammatory markers, and oxidative stress were also assessed. Additionally, the mRNA expression of paraoxonase 1 (PON-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC-1α) in cardiac and renal tissues was examined. Rats showed elevated serum lipid levels, renal and cardiac dysfunction, significant oxidative stress, and pro-inflammatory and apoptotic markers at the end of the study. Treatment with lycopene significantly corrected and restored these changes. Additionally, lycopene markedly increased the mRNA expression of PGC-1α and PON-1, and decreased PPAR-γ expression. It was determined that lycopene has the capacity to modulate the PPAR-γ and PON-1 signaling pathway in order to preserve the cellular energy metabolism of the heart and kidney, which in turn reduces tissue inflammatory response and apoptosis. According to these findings, lycopene may be utilized as a medication to treat hypercholesterolemia. However, further studies should be conducted first to determine the appropriate dose and any adverse effects that may appear after lycopene usage in humans.

This motive of current research is to provide a stochastic platform based on the artificial neural networks (ANNs) along with the Bayesian regularization approach for the fractional food chain supply system (FFSCS) with Allee effects. The investigations based on the fractional derivatives are applied to achieve the accurate and precise results of FFSCS. The dynamical FFSCS is divided into special predator category P(η), top-predator class Q(η), and prey population dynamics R(η). The computing numerical performances for three different variations of the dynamical FFSCS are provided by using the ANNs along with the Bayesian regularization approach. The data selection for the dynamical FFSCS is selected for train as 78% and 11% for both test and endorsement. The accuracy of the proposed ANNs along with the Bayesian regularization method is approved using the comparison performances. For the rationality, ability, reliability, and exactness are authenticated by using the ANNs procedure enhanced by the Bayesian regularization method through the regression measures, correlation values, error histograms, and transition of state performances.

A metabolic disease called hypercholesterolemia is connected to both oxidative damage and inflammation. The goal of the current investigation was to determine if olive oil and palm oil could prevent hypercholesterolemia-induced oxidative stress in the liver of rats fed a high-cholesterol diet (HCD). The experimental mice were given HCD for three months while also receiving 0.5 mL/kg of either palm or olive oil. Serum triglycerides, total cholesterol, LDL cholesterol, vLDL cholesterol, and the atherogenic index all significantly increased in HCD-fed rats, while HDL cholesterol significantly dropped. Additionally, HCD caused a notable rise in proinflammatory cytokines and serum transaminases in liver tissue. Additionally, HCD significantly increased the production of nitric oxide and lipid peroxidation in the liver while decreasing antioxidant enzymes. Treatment with palm and olive oils dramatically reduced the levels of pro-inflammatory cytokines and lipid peroxidation, improved antioxidant defenses, and considerably improved liver function indicators. Additionally, the examined oils dramatically decreased the expression of fatty acid synthase (FAS) in the liver of rats receiving HCD. In conclusion, HCD-fed rats exhibit significant antihyperlipidemic and cholesterol-lowering benefits from palm and olive oils. The improved antioxidant defenses, lower inflammation and lipid peroxidation, and altered hepatic FAS mRNA expression were the main mechanisms by which palm and olive oils produced their advantageous effects.

الهدف: ابراز دور الخضاب الغلوكوزي كمشعر لخطورة تطوّر اعتلال القلب السّكّري. طرق الدراسة والمرضى: في دراسة الحالة – ضابطة هذه، تم اختيار ما مجموعه 80 مريضًا مصابًا بالدّاء السّكري نمط 2 تتراوح أعمارهم بين 40-70 عامًا، من مستشفى تشرين الجامعي في الّلاذقيّة وتم تضمينهم في مجموعة الحالة، وتم مقارنتهم بـ80 مشاركًا غير مصابين بالسّكري كمجموعة ضابطة، تمت مطابقة المجموعتين من حيث: العمر، الجنس، ضغط الدم ومؤشر كتلة الجسم (BMI)، وتم فحص المجموعتين بتصوير القلب الصّدوي مع الدوبلر وتخطيط القلب الكهربائي، وخضعت المجموعتان لفحص سريري شامل وقياس ضغط الدم، مع اجراء مجموعة من التّحاليل المخبريّة الأساسيّة (يوريا، كرياتينين، غلوكوز الدم الصّيامي، تعداد عام وصيغة دمويّة)، وتم إجراء تحليل الخضاب الغلوكوزي (HBA1c) لمجموعة الحالة. النتائج: لوحظ في مجموعة الحالة وجود سوء الوظيفة الانبساطيّة لدى 66 مريضًا من أصل 80 (82.5٪)، وكانت درجات سوء الوظيفة الانبساطيّة 33 (50٪) للدرجة الأولى، 22 (33.3٪) للدرجة الثانية، 11 (16.7٪) للدرجة الثالثة، كانت قيمة HBA1c لدى 16 (20%) من مرضى مجموعة الحالة> 7، 19(23%) مع HBA1c بين 7.1-8، 11 (13.75%) مع HBA1c بين 8.1-9، 20 (25٪) مع 9HBA1c>، و14 (17.5٪) بدون سوء وظيفة انبساطيّة جميعهم لديه 7HBA1c

Background: In the COVID-19 era, efforts are being made to increase awareness among students and enhance best practices to mitigate the outbreak. To that end, the overarching aims of this study were to understand students’ attitude toward and knowledge of COVID-19 and examine the predictors of their attitude toward hand hygiene. Design and Methods: This cross-sectional survey study, conducted in Saudi Arabia, enrolled interns from diverse healthcare-related fields. The questionnaire was divided into three sections: sociodemographic data, knowledge of COVID-19, and attitude toward hand hygiene. The data was expressed as median and interquartile range (IQR). Results: In all, 371 responses were analyzed. The median knowledge score was 20, which was considered good. There were no statistically significant differences across age, hospital setting, or gender. Of the 254 respondents who had attended an educational session, 167 (65%) had a good knowledge score and 83 (33%) had a moderate score, compared with only four (2%) who had a poor score. The cumulative median score of the respondents’ attitudes was 6 (IQR [2]), which reflects a suboptimal attitude—only 38 (22%) reported a good attitude. The predicted effect of knowledge on attitude (good/suboptimal) was statistically significant (p = 0.02) using univariate logistic regression. Conclusions: The results suggest a strong need to encourage the current training program that targets hand hygiene practices among students in healthcare-related fields, especially prior to the internship year.

Abstract This study was designed to investigate the potential defensive strategy of Sana Makki extract (SME) against Cd-induced in vivo nephrotoxicity and its underlying mechanisms. Male albino rats were used in a thirty days study comparing control, SME-treated, CdCl2-treated, and combined SME and Cd treatment. Pre-treatment with SME significantly reduced serum kidney biomarkers (urea and creatinine), the concentration of renal KIM-1, and kidney index values. Additionally, SME also attenuated CdCl2-induced oxidative and nitrosative stress in renal tissue; significantly reducing malondialdehyde (MDA) and nitric oxide (NO) concentrations and significantly increasing antioxidant enzymes in kidney tissue. Molecularly, SME significantly upregulated antioxidant gene expression (SOD2, GR, GPx1, and CAT) caused by Cd. Notably, the augmented mRNA expression of nuclear-related factor 2 (Nrf2) by Cd was enhanced by SME administration. SME markedly suppressed the Cd-induced rise in pro-inflammatory cytokines. The combination of Cd and SME relieved the Cd-induced apoptotic damage by enhancing Bcl2 and suppressing Bax and Cas-3 levels in renal tissue. The renal tissue histoarchitecture confirmed the biochemical and molecular findings. Collectively, our data indicate that SME can counteract Cd-induced renal intoxication through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms.

Abstract Background Variable expressivity is a well-known phenomenon in which patients with mutations in one gene display varying degrees of clinical severity, potentially displaying only subsets of the clinical manifestations associated with the multisystem disorder linked to the gene. This remains an incompletely understood phenomenon with proposed mechanisms ranging from allele-specific to stochastic. Results We report three consanguineous families in which an isolated ocular phenotype is linked to a novel 3′ UTR mutation in SLC4A4, a gene known to be mutated in a syndromic form of intellectual disability with renal and ocular involvement. Although SLC4A4 is normally devoid of AU-rich elements (AREs), a 3′ UTR motif that mediates post-transcriptional control of a subset of genes, the mutation we describe creates a functional ARE. We observe a marked reduction in the transcript level of SLC4A4 in patient cells. Experimental confirmation of the ARE-creating mutation is shown using a post-transcriptional reporter system that reveals consistent reduction in the mRNA-half life and reporter activity. Moreover, the neo-ARE binds and responds to the zinc finger protein ZFP36/TTP, an ARE-mRNA decay-promoting protein. Conclusions This novel mutational mechanism for a Mendelian disease expands the potential mechanisms that underlie variable phenotypic expressivity in humans to also include 3′ UTR mutations with tissue-specific pathology.

The use of synthetic azo dyes as coloring agents in food products has dramatically increased. This study evaluated the effect of perinatal exposure to tartrazine (TZ) on mice offspring, focusing on neurobehavioral alterations and oxidative stress. The female mice received TZ (2.5 and 5 mg/kg) via oral gavage during pregnancy and the first 15 days after birth. At days 21 and 35 after birth, male mice were sacrificed, and samples were collected for analyses. Perinatal exposure to TZ triggered tissue injury evidenced by the histological alterations and neuronal damage in the cerebrum, medulla oblongata, and cerebellum. TZ provoked lipid peroxidation and diminished cellular antioxidants in different brain regions of the newborns. In addition, TZ increased hemoglobin content, as well as erythrocytes, leukocytes, and platelets count at days 21 and 35 after birth. Both the locomotor behavior and anxiety reflex were significantly altered in mice exposed to TZ. In conclusion, perinatal exposure to TZ within an adequate daily intake range induced oxidative stress and neurobehavioral and hematological alterations in mice offspring. Therefore, consuming foods containing TZ during pregnancy and lactation warrants public awareness.

Background: Osteoporosis is a chronic bone metabolic disease that affects millions of people worldwide, particularly the elderly and postmenopausal women. It is characterized by weakened bones, increasing the risk of fractures and leading to significant morbidity and mortality. The goal of the current study is to examine the reported osteo-preservative effects of exercise and/or fasting in the Ramadan fasting model (RFM) in ovariectomized (OVX) rats. Methods: The experimental intervention started 1 month following the ovariectomy procedure and consisted of five 15-min exercise sessions per week at 18–25 m/min and/or an approximately 13-h fast from sunrise to sunset (6:00 AM–19:00 PM). Serum bone metabolism biomarker levels were measured, and mineral concentrations in femoral ashed bones and digested serum were determined. Additionally, serum bone alkaline phosphatase (b-ALP), parathyroid hormone, osteocalcin, calcitonin, and vitamin D3 concentrations were measured using the competitive enzyme immunoassay technique. Results: Calcium, magnesium, and phosphorus showed a notable decrease in mineral concentration among OVX rat femurs compared with the combination group (OVX + RFM + E) and control groups. In addition, homeostasis of serum concentrations of calcium, magnesium, and phosphorus was observed to increase in the OVX + RFM + E group rather than in the OVX group without intervention when compared with a control group. Furthermore, fasting and exercise, either alone or concurrently with ovariectomy, induced a non-significant elevation in osteocalcin, parathyroid hormone, and vitamin D3, whereas b-ALP and calcitonin increased significantly compared with those in control rats. Conclusion: The combination of the Ramadan fasting model and moderate intensity exercises among OVX rats manifested advantageous effects in bone biomarkers compared with OVX rats without intervention. This could be recommended as a lifestyle modification that is protective against osteoporosis, especially in the context of depleted estrogen hormone after menopause. [ABSTRACT FROM AUTHOR]