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Energy and daylight simulations can be computationally intensive and time consuming, especially if their main aim is to inform the design process in the early stages. In addition, the collaboration between different disciplines have become even more important to ensure that the building design can successfully reach low carbon and energy targets while ensuring good daylight levels. This research proposes an investigation about a new methodology to run both daylight and energy simulations simultaneously while optimizing the façade parameters to find the best solutions for good daylight, low energy demand and low carbon emissions from the energy use. Overall, the outcomes demonstrated that the support of multi-objective optimization engines could successfully assist in choosing between different facade solutions with high performance indicators. Moreover, it is possible to rank the different results according to their key performance indicator (KPI), so the architects have more options to choose.

Abstract Background Flaxseed has recently gained attention in the area of cardiovascular disease primarily because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Although the benefits of exercise on any single risk factor are unquestionable, the effect of exercise on overall cardiovascular risk, when combined with other lifestyle modifications such as proper nutrition, can be dramatic. This study was carried out to evaluate the protective role of flaxseed and exercise on cardiac markers, lipids profile and inflammatory markers in isoproterenol (ISO)-induced myocardial ischemia in rats. Methods The research was conducted on 40 male albino rats, divided into 4 groups (n=10): group I served as control, group II has acute myocardial ischemia induced by isoproterenol, groups III and IV have acute myocardial ischemia induced by isoproterenol pretreated with flaxseed supplementation orally for 6 weeks, additionally group IV practiced muscular exercise through swimming. Results Alterations of lipid profile, cardiac and inflammatory markers (Il-1β, PTX 3 and TNF- α) were observed in myocardial ischemia group. Flaxseed supplementation combined with exercise training showed significant increase of HDL and PON 1, on the other hand cardiac troponin, Il- 1β and TNF- α levels significantly decreased as compared to myocardial ischemic group. Receiver Operating Characteristics (ROC) analysis of cTnI, PTX 3, Il-1β and TNF- α revealed a satisfactory level of sensitivity and specificity. Conclusion Regular exercise enhances the improvement in plasma lipoprotein levels and cardiovascular protection that results from flaxseed supplementation by mitigating the pathophysiology of atherosclerosis. Elevation of HDL, the antioxidant PON 1 and the cardioprotective marker PTX 3 emphasizes the protective effects of flaxseed and muscular exercise mutually against the harmful effects of acute myocardial ischemia.

Abstract Background The purpose of this report is to assess the safety and efficacy of single lower pole access for multiple and branched renal calculi. A prospective non randomized clinical study included 26 patients with complex renal stones (9 patients had branched renal stones and the other 17 had multiple renal stones) in the period from May 2003 to May 2004. Mean patient age was 42 years ± 13.2 (range 18 to 67 years). All patients underwent percutaneous nephrolithotomy (PCNL) via a single lower calyceal puncture. Small stones were intactly extracted by a range of stone graspers while large stones (smallest diameter more than 1 cm) were disintegrated using either the pneumatic EMS Swiss lithoclast or Holmium YAG laser. Flexible nephroscope was used for stones inaccessible by the rigid instruments. Findings Overall stone-free rate was 74.8%. Patients with residual stones were managed by one session of shock wave lithotripsy (SWL). Mean operative time was (80 minutes ± 27.4) for branched stones and (49.1 minutes ± 15.9) for multiple stones. No significant blood loss reported. Perforation of pelvicalyceal system occurred in 2 patients (11.5%) with no serious sequelae. Only 1 patient developed secondary hemorrhage which necessitated blood transfusion and selective angio-embolization. Conclusion In our hands, the efficacy and safety of single lower calyceal puncture PCNL in management of complex renal stones are comparable to those of the general procedure stated in literature.

Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS)., Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS., Results: We identified homozygous missense variants in MYO1C in two unrelated children with NS (c.292C > T, p.R98W; c.2273 A > T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1C to be predominantly expressed in podocytes. We then performed structural modeling for the identified variants in PyMol using aligned shared regions from two available partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the myosin motor domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants., Conclusion: We here identified recessive variants in MYO1C as a potential novel cause of NS in children., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

This paper addresses the problem of decentralized, collaborative state estimation in robotic teams. In particular, this paper considers problems where individual robots estimate similar physical quantities, such as each other's position relative to themselves. The use of pseudomeasurements is introduced as a means of modeling such relationships between robots' state estimates and is shown to be a tractable way to approach the decentralized state estimation problem. Moreover, this formulation easily leads to a general-purpose observability test that simultaneously accounts for measurements that robots collect from their own sensors, as well as the communication structure within the team. Finally, input preintegration is proposed as a communication-efficient way of sharing odometry information between robots, and the entire theory is appropriate for both vector-space and Lie-group state definitions. To overcome the need for communicating preintegrated covariance information, a deep autoencoder is proposed that reconstructs the covariance information from the inputs, hence further reducing the communication requirements. The proposed framework is evaluated on three different simulated problems, and one experiment involving three quadcopters., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Multisystemic inflammatory syndrome (Mis-C) has emerged in May 2020 as a serious complication of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). A total of 6 children presented to tertiary care hospitals with Mis-C, of which 5 (83%) have died during hospitalization. All included patients presented with respiratory symptoms (ranged from mild to severe acute respiratory distress syndrome) and gastrointestinal symptoms. Most of the patients are known to have medical illnesses. Pediatric Risk of Mortality (PRISM) IV score ranged from 3 to 87. All patients developed acidosis and varying stages of acute kidney injury and electrolyte disturbances. All were treated for coagulopathy, thrombocytopenia, bacterial infections as well as antiviral medications (either ritonavir or lopinavir). Most patients had chest X-ray changes either unilateral or bilateral lung changes. Multisystemic inflammatory syndrome is a rare, yet serious complication of SARS-CoV2 infection in children. Multisystem involvement should be anticipated and promptly treated., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Canine parvovirus type 2 (CPV-2) is a major cause of fatal gastroenteritis and myocarditis in puppies of domestic and wild carnivores. CPV-2 has accumulated changes over time lead to the emergence of three antigenic variants CPV-2a, CPV-2b, and CPV-2c. VP2 is the major capsid protein that determines virus antigenicity, and host range. Although the three CPV-2 variants were previously identified in Egypt, most reports covered a restricted geographic region and/or time period, and only analyzed partial fragments of VP2 gene. Therefore, this study was designed to test 100 rectal swabs collected from 7 Egyptian governorates between 2019 and 2021 for CPV-2 using PCR. A total of 65 positive samples were identified, mostly in pure dog breeds of young age. The three variants co-circulated in 2019, while CPV-2b was not detected in 2020 and 2021. The frequency of CPV-2b and CPV-2c was higher in 2019 and 2021, respectively. Analysis of CPV-2 full-length VP2 gene sequence from 19/65 positive samples has identified four common amino acid substitutions F267Y, S297A, A300G, Y324I, which are characteristic for the new CPV-2 variants currently circulating worldwide. Unique substitutions including A5G, G36R, V38E, Q370R, and G392V were recognized in certain samples, and appears to have distinct effect on receptor binding, nuclear translocation, and inter-species transmission. Phylogenetic analysis showed separation of CPV-2 strains into two clades. All strains of this study were classified in clade I with Asian strains. In conclusion, this study provides updated comprehensive molecular analysis of CPV-2 variants in Egypt., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Feed additives are products used in poultry nutrition to improve the quality of feed and the safety of food byproducts from animal origin. They are promising antibiotic alternatives for the production of broilers., Aim: This study aimed to investigate the effect of sodium butyrate (SB) and RL on growth performance, biochemical profile, immunity, and carcass traits of broilers., Methods: Five hundred-one-day-old chicks of the Hubbard breed were reared on floor pens in a privet farm, Giza. The chicks were weighed on arrival (each chick weighted 43-45 gm) and randomly assigned into five equal groups, with four replicates each (25 chicks/replicate). Group 1 was fed on a broiler diet without any additions (control). The diets of groups 2 and 3 were supplemented with 500 g/ton SB and 4 kg/ton RL, respectively. In group 4, the diet was enriched with 250 g/ton SB plus 2 kg/ton RL. Chicks in group 5 were fed on a diet fortified with 500 g/ton SB plus 4 kg/ton RL., Results: Supplementation of broiler diet with 500 g/ton SB plus 4 kg /ton RL increased body weight gain (BWG) and feed efficiency ratio (FER) of birds. It decreased serum levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol triglycerides, and malondialdehyde, but increased superoxide dismutase, catalase, and immunoglobulins, phagocytic activity, lysozyme activity, and nitric oxide concentrations. Antibody titers against the Newcastle disease virus were also elevated., Conclusion: Supplementation of broiler diet with 500 g/ton SB plus 4 kg/ton RL gives the best result regarding productive efficiency and immunity of broiler chickens., Competing Interests: All authors declare that there are no conflicts of interest.

Background: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities., Methods: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities., Results: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD)., Conclusions: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Thienothiophene (TT) has received great attention in the fields of electronics and optoelectronics. Here we report a synthesis and characterization of fullerene-donor-fullerene triads linked to thieno[2,3- b ]thiophene as a donor. The photophysical and electrochemical properties of the new dumbbells were investigated using UV-vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and square wave voltammetry. The results showed that both compounds have higher LUMO energy levels than PC 61 BM, indicating that they can be used in photovoltaic applications. Furthermore, the powder was structurally and morphologically characterized via X-ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM revealed the morphological characterization of the two derivatives as globular and urchin-like supramolecular assemblies.

In this study, we synthesized (2-propoxyphenyl)(3-( p -tolyl)oxiran-2-yl)methanone through oxidizing the double bond of the respective chalcone via the Weitz-Scheffer epoxidation reaction. Additionally, the chalcone with an oxirane ring served as a fundamental building block for the synthesis of various pyrazole and imidazole derivatives, employing diverse nitrogen nucleophiles. All synthesized compounds were confirmed via analytical and spectroscopic analysis, such as FT-IR, 1 H NMR, 13 C NMR, and mass spectroscopy. Furthermore, all these nitrogen heterocycles were optimized via the DFT/B3LYP/6-31G(d,p) basis set and their physical descriptors were identified. Compound 11 was further confirmed using single-crystal X-ray diffraction with Hirshfeld analysis, and the results were correlated with the optimized structure by comparing their bond length and bond angle, which provided excellent correlation. Additionally, the insecticidal activities of the newly synthesized compounds were tested against P. interpunctella and Nilaparvata lugens . The heterocyclic compounds exhibited remarkable activity compared to the standard reference thiamethoxam. These findings were further confirmed through docking simulation with different proteins, namely PDBID 3aqy and 3wyw. The compounds interacted effectively within the protein pockets, displaying a higher binding energy with amino acids., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

There is no consensus regarding mitral valve management during surgical ventricular restoration (SVR) for ischemic cardiomyopathy. We compared the impact of SVR with mitral valve repair (MVr) vs replacement (MVR) on postoperative outcomes and long-term survival in ischemic cardiomyopathy and mitral regurgitation patients. This study included 112 patients who underwent SVR from 2009 to 2018 with MVr (n = 75) or MVR (n = 37). Patients who had MVR had higher Euro SCORE II, dyspnea class, a lower ejection fraction, higher pulmonary artery systolic pressure, higher grade of preoperative mitral and tricuspid regurgitation, and higher end-diastolic and end-systolic diameters. Intra-aortic balloon pump was more commonly used in patients with MVR. Hospital mortality occurred in 7 (9.33%) patients in the MVr group vs 3 (8.11%) in the MVR group (P > .99). Freedom from rehospitalization at 1, 5, and 7 years was 87%, 76%, and 70% in the MVr group and 83%, 61%, and 52% in the MVR group (P = .191). Survival at 1, 5, and 7 years was 88%, 78%, and 74% in the MVr group and 88%, 56%, and 56% in the MVR group (P = .027). Adjusted survival did not differ between groups.MVr or MVR are valid options in patients undergoing SVR, with good long-term outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The growing interest in employing nano-sized pharmaceutical formulations in veterinary medicine has prompted the exploration of the novel nanocarriers' ability to augment the therapeutic outcome. In this study, we harnessed niosomes, spherical nanocarriers formed through non-ionic surfactant self-assembly, to enhance the therapeutic efficacy of the broad-spectrum antibiotic florfenicol. Pre-formulation studies were conducted to identify the optimal parameters for preparing florfenicol-loaded niosomes (FLNs). These studies revealed that the formulation that consisted of Span 60, cholesterol, and dihexadecyl phosphate (DDP) at a molar ratio of 1:1:0.1 exhibited the highest entrapment efficiency (%EE) and uniform size distribution. In vitro antibacterial testing demonstrated the niosomal capacity to significantly reduce florfenicol minimum inhibitory concentration (MIC) against E. coli and S. aureus. Pharmacokinetic profiles of free florfenicol and FLN were assessed following oral administration of 30 mg florfenicol/kg body weight to healthy or E. coli-infected chickens. FLN exhibited a substantially higher maximum plasma concentration (C max ) of florfenicol compared to free florfenicol. Furthermore, FLN showed significantly higher area under the curve (AUC 0-t ) than free florfenicol as revealed from the relative bioavailability studies. Lethal dose (LD) 50 values for both free florfenicol and FLN exceeded 5 g/kg of body weight, indicating high safety profile. Assessment of mortality protection in mice against lethal E. coli infections showed the significantly higher capability of FLN to improve the survival rate (75%) than free florfenicol (25%). Collectively, these findings demonstrate the niosomal ability to improve the oral bioavailability as well as the antibacterial activity of the incorporated veterinary antibiotic florfenicol., (© 2023. The Author(s).)

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly ( P  < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society for Parasitology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Ethnopharmacological Relevance: Maca root (Lepidium meyenii Walp.) is a Peruvian plant of the Brassicaceae family. Maca roots are popular food supplements used to treat a variety of ailments described traditionally as enhancing metabolic and health conditions., Aim of the Study: Metabolic syndrome (MetS) has been the real scourge globally, affecting more than one-fourth of the global population. MetS causes the development of multi-organ illnesses, including altered blood cholesterol and sugar levels, oxidative stress, and hypertension. This study evaluated maca root total methanolic extract (MTE) as a potential nutraceutical to manage the complications of MetS., Materials and Methods: After the first 4 weeks of a high-fat high-carbohydrate diet (HFCD), streptozotocin (STZ) was injected in Wistar rats to induce the MetS model. Animals were treated orally with MTE at 100 mg/kg and 300 mg/kg for 4 weeks compared to metformin at 200 mg/kg after confirmation of diabetes., Results: One month of MTE supplementation in HFCD-fed rats remarkably decreased the elevation of blood glucose and lipids, improved liver function and insulin resistance, additionally it successfully restored the state of inflammatory and oxidative stress. The extract was standardized to contain total phenolics equal to 24.45 ± 0.96 μg Gallic acid/mg extract., Conclusions: Our findings suggest that MTE improves MetS by reducing hyperglycemia, hyperlipidemia, inflammation, and oxidative stress. While also improving beta cell secretory functions, implying that MTE could be used as a balancing drug in the prevention and treatment of metabolic abnormalities linked to type 2 diabetes., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of kidney failure in children and adults under the age of 20 years. Previously, we were able to detect by exome sequencing (ES) a known monogenic cause of SRNS in 25-30% of affected families. However, ES falls short of detecting copy number variants (CNV). Therefore, we hypothesized that causal CNVs could be detected in a large SRNS cohort., Methods: We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in whom we previously did not identify a genetic cause through ES. We evaluated ES and CNV data for variants in 60 known SRNS genes and in 13 genes in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria for CNV evaluation., Results: We detected a novel CNV in two genes in 2 out of 138 families (1.5%). The 9,673 bp homozygous deletion in PLCE1 and the 6,790 bp homozygous deletion in NPHS2 were confirmed across the breakpoints by PCR and Sanger sequencing., Conclusions: We confirmed that CNV analysis can identify the genetic cause in SRNS families that remained unsolved after ES. Though the rate of detected CNVs is minor, CNV analysis can be used when there are no other genetic causes identified. Causative CNVs are less common in SRNS than in other monogenic kidney diseases, such as congenital anomalies of the kidneys and urinary tract, where the detection rate was 5.3%. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Organ transplantation is inherently dependent on the availability of organ donors. There is a noticeable paucity of literature addressing the rates of organ donation registration and the awareness of Islamic regulations (Fatwa) regarding organ donation within Saudi Arabia. Our study aimed to evaluate the level of organ donation registration, awareness of Islamic regulations, and knowledge of the Saudi Center for Organ Transplantation (SCOT) within the Saudi society., Methods: We conducted a cross-sectional survey from 30 March to 9 April 2023. This survey aimed to assess the awareness of Islamic (Fatwa) guidance on organ donation, the role of SCOT, and the rate of organ donation registration facilitated through the Tawakkalna app, the official health passport application in Saudi Arabia., Results: Out of 2329 respondents, 21% had registered as potential deceased organ donors, despite 87% acknowledging the importance of organ donation. Awareness of the Islamic Fatwa regarding organ donation was reported by 54.7% of respondents, and 37% recognized the Fatwa's acceptance of brain death criteria. The likelihood of registration as organ donors was higher among Saudi citizens under 45 years of age, females, healthcare workers (HCWs), individuals with higher education, relatives of patients awaiting organ donations, those informed about the Islamic Fatwas, and those willing to donate organs to friends. Conversely, being over the age of 25, Saudi nationality, employment as an HCW, awareness of SCOT, and prior organ donation registration were predictive of a heightened awareness of Islamic Fatwas. However, perceiving the importance of organ donation correlated with a lower awareness of the Fatwas. Significant positive correlations were found between awareness of SCOT, awareness of Fatwas, and registration for organ donation., Conclusions: While the Saudi population exhibits a high regard for the importance of organ donation, this recognition is not adequately translated into registration rates. The discrepancy may be attributable to limited awareness of SCOT and the relevant Islamic Fatwas. It is imperative to initiate organ donation awareness campaigns that focus on religious authorization to boost organ donation rates and rectify prevalent misconceptions.

Disruption of GABAergic signaling could exaggerate the inflammatory reaction associated with Toxoplasma gondii infection, as well as produce neurophysiological consequences including seizures that occur within the brain tissues. The current study aimed to evaluate the efficacy of ivermectin (IVM) in treating latent cerebral toxoplasmosis and define its role in the neuromodulation of cerebral tissue GABA expression, conducted in an immunocompromised dexamethasone-treated mouse model infected with the ME49 Toxoplasma strain. The control (non-infected non-treated) group showed a mean of 22.1 ± 0.71 for local expression of GABA. Significantly lower expression (3.78 ± 1.38) was recorded in the infected non-treated group ( p  ≤ 0.05). On the contrary, a significantly higher expression was reported in the group infected and treated with IVM than in the infected non-treated group (19.8 ± 0.8). While the infected spiramycin (SP)-treated group reported a significantly lower level than the control. Non-infected groups that received only IVM or SP recorded 22.3 ± 0.45 and 22 ± 0.89 respectively with no significant difference. IVM is shown in this work, not only to reduce the size and the number of Toxoplasma cystic lesions within the brain significantly with a reduction rate of 68.85% but to also increase the level of GABA local expression significantly in addition to improving cerebral histopathology. Thus, IVM by its ability to modulate GABA expression may improve such clinical situations, if used as a treatment either exclusively or in combination with other medications., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society for Parasitology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT. CHRM5 codes for a seven transmembrane-spanning G-protein-coupled muscarinic acetylcholine receptor. CHRM5 is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in Chrm5 knockout mice. We investigated CHRM5 as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with CHRM5 variants could help to further assess the genes' candidate status., (© 2023 Wiley Periodicals LLC.)

Chalcones are a group of naturally occurring compounds that have biological effects that include anti-inflammatory, anti-cancer, and antibacterial properties. Current chalcone research, including their synthesis, structure-activity relationships, and biological activities, is summarized herein. Along with their toxicity and safety profiles, the prospective usage of chalcones in medicinal research and development is discussed. This review emphasizes the need for additional research in order to fully examine the therapeutic potential of chalcones as therapeutic agents for the treatment of a variety of disorders.

Background: Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure., Methods: A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Saudi Arabia. Detailed clinical molecular diagnosis was performed for 25 affected individuals. Whole exome sequencing (WES)-based molecular diagnosis was performed for all affected individuals., Results: The male:female ratio was 52% male (n = 13) and 48% female (n = 12), and consanguinity was present in 88%. Nephrolithiasis and/or nephrocalcinosis were present in all patients. Kidney stones were present in 72%, nephrocalcinosis in 60%, hematuria in 32%, proteinuria in 16%, abdominal pain in 36%, developmental delay in 8%, and chronic kidney disease stage 5 (CKD stage 5) was observed in 28% of the patients. The most common PH disorder was type I caused by variants in the AGXT gene, accounting for 56%. The GRHPR gene variants were identified in 4 patients, 16% of the total cases. Seven patients did not reveal any associated variants. Missense variants were the most commonly observed variants (48%), followed by frame-shift duplication variants (28%)., Conclusions: Characterization of the genetic and clinical aspects of PH in this unique population provides direction for improved patient management and further research. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s).)

Cerebral toxoplasmosis is an opportunistic infection, occurring mostly in immunosuppressed patients due to the reactivation of latent Toxoplasma cysts. The cerebral comorbidity in diabetic patients tends to intensify the burden of pathogenic infection within the brain. The aim of this work was to study the effect of cerebral toxoplasmosis in experimentally infected hyperglycemic mice, on histopathology and glial fibrillary acidic protein (GFAP) expression, compared to normoglycemic mice at different time intervals. Vasculopathy was exclusively observed in diabetic groups, with features of increased severity during Toxoplasma infection. Gliosis was observed in diabetic groups, while hyperactive astroglial activity was detected in normoglycemic groups, especially at 6 weeks of infection. GFAP expression showed significant up-regulation in normoglycemic mice at 6 weeks of infection (40.03 ± 1.41) afterwards, it decreased to 22.22 ± 3.14 at 12 weeks which was statistically insignificant to the normal level, possibly indicating the successful Toxoplasma stage transformation (to bradyzoite), thereby limiting the infection within the brain. In hyperglycemic infected groups, GFAP was significantly down-regulated, in both acute and chronic phases of infection, most likely indicating failure of stage transformation and infection limitation. This may expose those vulnerable groups to the risk of dissemination, resulting in life-threatening diffuse encephalitis . The current study emphasized the importance of rapid diagnosis of Toxoplasma infection in diabetic subjects, and highlighted the value of using GFAP as a neurological indicator of disease progression in those comorbid cases., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society for Parasitology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The wide spread of nanotechnology applications currently carries with it the possibility of polluting the environment with the residues of these nanomaterials, especially those in the metallic form. Therefore, it is necessary to study the possibility of treating and removing various nanoscale metal pollutants in environmentally friendly ways. The present study focused on the isolation of multi-metal tolerant fungi to be applied in the bioremoval of Zn, Fe, Se, and Ag nanoparticles as potential nanoscale metal pollutants. Aspergillus sp. has been isolated as multi-metal tolerant fingus and investigated in the bioremoval of targeted nanometals from their aquoues solutions. The effect of biomass age, pH, and contact time was studied to determine the optimal biosorption conditions for fungal pellets towards metal NPs. The results showed a high percentage of fungal biosorption on the of two-day-old cells, which amounted to 39.3, 52.2, 91.7, and 76.8% of zinc, iron, selenium, and silver, respectively. The pH 7 was recorded the highest percentage of NPs removal for the four studied metals i.e. 38.8, 68.1, 80.4, and 82.0% of Zn-, Fe-, Se- and Ag-NPs, respectively. The contact time required between Aspergillus sp. and the metal nanoparticles to obtain the best adsorption was only 10 min in the case of Zn and Ag, but it was 40 min for both Fe and Se NPs. The efficiency of living fungal pellets in removing the four metallic NPs exceeded that of dead biomass by 1.8, 5.7, 2.5, and 2.5 folds for Zn, Fe, Se and Ag, respectively. However, utilization of dead fungal biomass for metallic NPs removal could be considered more applicable to the actual environmental applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Heterocyclic scaffolds are frequently employed in drug development to treat a variety of conditions, including cancers. These substances have the ability to engage covalently or non-covalently with particular residues in the target proteins, inhibiting them. In this study, the formation of N-, S-, and O-containing heterocycles by the interaction of chalcone with nitrogen-containing nucleophiles such as hydrazine, hydroxyl amine, guanidine, urea, and aminothiourea was explored. FT-IR, UV-visible, NMR, and mass spectrometric studies were used to confirm the heterocyclic compounds that were produced. These substances were tested for their antioxidant activity by their capacity to scavenge the artificial radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH). The strongest antioxidant activity was demonstrated by compound 3 (IC 50 = 93.4 μM), whereas compound 8 (IC 50 = 448.70 μM) had the lowest activity when compared to vitamin C (IC 50 141.9 μM). Also, the experimental findings and the docking estimation of these heterocyclic compounds with PDBID:3RP8 were in agreement. Additionally, the compounds' global reactivity characteristics, such as HOMO-LUMO gaps, electronic hardness, chemical potential, electrophilicity index, and Mulliken charges, were identified using DFT/B3LYP/6-31G(d,p) basis sets. The two chemicals that displayed the best antioxidant activity also had their molecular electrostatic potential (MEP) ascertained using DFT simulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: COVID-19 is a respiratory disease that eventually became a pandemic, with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently been reported to help in early prediction and managing severe cases, which might improve outcomes. Our study aimed to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in COVID-19 patients and its effect on the outcome. Methods: We have collected retrospective data on socio-demographics, medical history, biomarkers, and disease outcomes from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID-19 in our cohort. The presence of abnormal inflammatory biomarkers (D-dimer, CRP, troponin, LDH, ferritin, and t white blood cells) was significantly associated with unstable COVID-19 disease. In addition, patients with evidence of severe respiratory disease, particularly those who required mechanical ventilation, had higher biomarkers when compared to those with stable respiratory conditions ( p < 0.001). Conclusion: Identifying biomarkers predicts outcomes for COVID-19 patients and may significantly help in their management.

In this investigation, pressure microwave irradiation was used to clarify the activity of 1-(2-hydroxyphenyl)-3-(4-methylphenyl)prop-2-en-1-one (3) towards several active methylene derivatives utilized the pressurized microwave irradiation as green energy resource . Chalcone 3 was allowed to react with ethyl cyanoacetate, acetylacetone, and thioglycolic acid; respectively, at 70 °C with pressure under microwave reaction condition to afford the corresponding 2-hydroxyphenylcyanopyridone, 2-hydroxyphenyl acetylcyclohexanone, and thieno[2,3-c]chromen-4-one derivatives respectively. Moreover, the reaction of chalcone 3 with hydrogen peroxide with stirring affords the corresponding chromen-4-one derivative. All the synthesized compounds were confirmed through spectral tools such as FT-IR, 1 HNMR, 13 CNMR, and mass spectrum. Furthermore, the synthesized heterocycles were exhibited excellent antioxidant activity and comparable with vitamin C, where the presence of the OH group increases the scavenger radical inhibition. Furthermore, the biological activity of compound 12 was demonstrated through molecular docking stimulation using two proteins, PDBID: 1DH2 and PDBID: 3RP8, which showed that compound 12 possesses greater binding energy and a shorter bond length comparable with ascorbic acid. Also, the compounds were optimized through DFT/B3LYP/6-31G (d,p) basis set and identification of their physical descriptors, whereas the compound 12 was confirmed through X-Ray single structure with Hirsh field analysis of the compound to know the hydrogen electrostatic bond interaction, and correlated with the optimized structure by comparing their bond length, bond angle, FT-IR, and NMR, which gave excellent correlation., (© 2023. The Author(s).)

Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 - 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

Alzheimer's disease (AD) is one of the neurodegenerative illnesses that impair individual life & increase the demand for caregivers with no available curative medication right now. Therefore, there is a growing concern about employing herbal medicine to limit AD progression & improve patients' life quality, thus potentiating its add-on therapy. In addition, herbs are cost-effective & accessible with nearly no side effects. In the same vein, our study aimed to investigate the potency of Echinacea purpurea (EP) flower extracts to ameliorate the neurodegenerative effect of Aluminum chloride (AlCl3) in a rat model. Moreover, mechanistic studies, including impact on the cholinesterase activity, redox status, inflammatory mediators, behavior performance, glucose level & histopathology, were carried on. Our results showed that 250 mg/kg of Aqueous (AQ) & Alcoholic (AL) extracts of EP inhibited cholinesterase, restored oxidative balance, down-regulated IL-6 & TNF-α cytokines & improved behavior performance in vivo that was reflected in the brain picture by decreasing neuronal degeneration & amyloid plaques in cerebral cortex & hippocampus. The potency of both extracts was compared to reference drugs & AlCl3 positive control group. The AQ extract showed greater potency against COX-1, COX-2 & α-amylase in vitro, while the AL extract was more potent against cholinesterase in vitro, inflammatory cytokines, behavior & pathological improvement in vivo. Conclusively EP overcame AlCl3-induced neurobehavioral toxicity in the rat model via different pathways, which support its regular administration to postpone progressive neural damage in AD patients., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Equid alphaherpesvirus 1 (EHV-1) is an important virus causing pathological disorders in horses. This highly contagious pathogen causes persistent outbreaks of upper respiratory tract infection, ocular affections, abortion, and neurological disorders with high mortality in Arabian horses in Egypt. The quick and accurate diagnosis is important to broaden our understanding about EHV-1 in the field, and to implicate stronger preventive, and control measures. Sixty-six Arabian horses from Cairo and Giza governorates were sampled from respiratory, abortigenic and neurological outbreaks over a period of 4 years. EHV-1 was diagnosed in these cases by immunohistochemistry using monoclonal antibody against EHV-1 glycoprotein B and molecular detection using gB, ORF33 specific real-time PCR. EHV-1 was detected in 25 cases, mostly from abortigenic outbreaks (14 abortions, 3 stillbirths, and two early neonatal deaths), in addition to 5 respiratory affections and single EHV-1 myeloencephalopathy. Molecular characterization revealed that the ORF33 sequences from this study were almost identical and closely related to the European EHV-1 strains. Furthermore, no difference in the amino acid sequences compared to previously published EHV-1 sequences from Egypt. The data in this study provides some insights about the prevalance of EHV-1 infection in Arabian horses, discusses EHV-1 diagnostic approaches, highlights the importance of accurate diagnosis and the importance of pregnant mare vaccination, and adds to the previous knowledge about EHV-1 in Egypt which may help in better controlling EHV-1 infections in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Cryptosporidium is a widely distributed food and water-borne enteric protozoan that affects a wide range of vertebrates, resulting in life-threatening consequences, particularly in immunocompromised hosts. The lack of effective anti-cryptosporidial drugs may be related to the parasite's unique intestinal location, plus the lack of studies on the process by which the protozoan is able to impair intestinal cellular function. The present work aimed to assess the effect of clofazimine (CFZ), an FDA-approved drug for the treatment of leprosy, as an anti-cryptosporidial drug, using transmission electron microscopy (TEM) and an immunocompromised mouse model. The affected intestinal mucosa with parasitic stages in the infected non-treated group showed signs of severe cellular degeneration, including the loss of tight junctions, deformed and damaged microvilli and irregularly distributed nuclei with a severely vacuolated cytoplasm. Comparatively, nitazoxanide (NTZ) monotherapy showed the lowest efficacy as the drug was associated with the lowest rate of oocyst shedding. In addition, NTZ treatment failed to achieve the return of complete cellular function; abnormalities were evident in the microvilli, cytoplasmic organelles and nuclear features. Clofazimine demonstrated an improvement of the mucosal cellular components, including mitochondria and significantly reduced oocyst shedding. Combined treatment with low-dose CFZ and half-dose NTZ resulted in a significant improvement in the enterocyte cellular structures with an absence of intracellular parasitic stages. These results indicate that CFZ, a safe and readily prescribed drug, effectively reduces cryptosporidiosis when used in combination with only half the dose of NTZ. Used in combination, these drugs were shown to be efficient in regaining intestinal cellular activity following Cryptosporidium- induced functional damage in an immunocompromised mouse model., Competing Interests: The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2022 The Authors.)

Nile Tilapia fish scale collagen has high biodegradability, excellent biocompatibility, and low antigenicity. We assessed both the encapsulation efficiency of theophylline into Nile Tilapia fish scale-based collagen nanoparticles and their stability as a pulmonary drug delivery system in male Sprague-Dawley rats. The present study has demonstrated the successful encapsulation of theophylline into the synthesised nanoparticles as shown by spectrophotometric analysis, light microscope, scanning electron microscope, transmission electron microscope, and dynamic light scattering. The antibacterial activity of the nanoparticles improves with increasing their concentrations. Intratracheal treatment of rats using theophylline-encapsulated nanoparticles reduced the levels of creatinine, alanine transaminase, and aspartate transaminase, compared to the control group. Nevertheless, nanoparticles combined with theophylline exhibited no effects on cholesterol and triglycerides levels. Histopathological examination revealed typical uniform and diffuse thickening of the alveolar walls with capillary oedema in treated rats. We concluded that the synthesised collagen nanoparticles appropriately target the lungs of male Sprague-Dawley rats when delivered via a nebuliser, showing good tolerability to lung cells. However, dose ratio of collagen nanoparticles to theophylline needs further evaluation. The nanoprecipitation method may be optimised to involve poorly water-soluble inhaled drugs, and avoid the drawbacks of traditional drug delivery., (© 2022. The Author(s).)

Background: Objective to assess the value of preoperative tranexamic acid (TXA) in reduction of intraoperative and postoperative blood loss in high-risk cesarean delivery (CD)., Methods: A double blind randomized controlled trial included 160 high risk women who underwent elective lower segment CD. They were equally randomized to receive either 1 g of TXA or placebo 15 min before surgery. The primary outcome was Intraoperative blood loss., Results: The estimated blood loss was significantly higher in the placebo group when compared to TXA group (896.81 ± 519.6 vs. 583.23 ± 379.62 ml, P < 0.001). Both postoperative hemoglobin and hematocrit were lower (9.2 ± 1.6 and 27.4 ± 4.1 vs. 10.1 ± 1.2 and 30.1 ± 3.4, P values < 0.001and 0.012 respectively) and their change percentages (15.41 vs. 7.11%, P < 0.001) were higher in the placebo group when compared to TXA one. The need for further ecbolics was higher in placebo group when compared to TXA group (46.25 vs. 13.75%, P < 0.001)., Conclusion: Preoperative TXA is safe and effective in reducing blood loss during and after high-risk CD., Trial Registration: ClincalTrial.gov ID: NCT03820206 ., (© 2022. The Author(s).)

Background: Renal stones (nephrolithiasis and urolithiasis) and nephrocalcinosis are uncommon in children; however, their incidences in pediatric populations have been increasing. Patients and Methods: This multicenter retrospective study compared the clinical presentation, etiology, and outcomes of childhood nephrolithiasis or urolithiasis with those of nephrocalcinosis. Results: The study included 144 children: 93 with renal stones and 51 with nephrocalcinosis. The mean age at presentation was 72 months and 54 months for children with renal stones and nephrocalcinosis, respectively. A history of consanguinity was found in 65% and 76% of the cases of renal stones and nephrocalcinosis, respectively. Congenital anomalies of the kidneys and urinary tract (CAKUT) were present in 28 and 9.8% of the patients with renal stones and nephrocalcinosis, respectively. The most common symptoms of renal stones were flank pain (29%), hematuria (15%), and dysuria (11%). Urinary tract infection was the primary presentation in the nephrocalcinosis group (18%), followed by failure to thrive (16%), polyuria (12%), and dehydration (12%). The majority of renal stone cases were caused by metabolic disorders, including hyperoxaluria (18%), cystinuria (18%), hypercalciuria (12%), and hyperuricosuria (2%). In contrast, the most common underlying disorders in cases of nephrocalcinosis were familial hypomagnesemia, hypercalciuria, nephrocalcinosis (35%), distal renal tubular acidosis (23%), and Bartter syndrome (6%). Clinical outcomes were significantly better in children with nephrolithiasis/urolithiasis than in those with nephrocalcinosis, who showed radiological evidence of worsening/persistent calcinosis and progressed more frequently to chronic kidney disease (stage II-IV) and end-stage kidney disease. Conclusion: The average age at presentation for children with renal stones was greater than that for those presenting with nephrocalcinosis. More than 25% of the children with renal stones were found to have CAKUT. Nephrocalcinosis was associated with worse clinical outcomes related to kidney function and disease resolution than nephrolithiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alhasan, Shalaby, Albanna, Temsah, Alhayek, Abdalla, Alotaibi, Kalakattawi, Zaher and Kari.)

Objectives: To study childhood nephrolithiasis and nephrocalcinosis caused by metabolic disorders, distal renal tubular acidosis (dRTA), and familial hypomagnesemia, hypercalciuria, and nephrocalcinosis (FHHNC)., Methods: We retrospectively evaluated 86 children presented over 10 years (2011-2021), with nephrolithiasis (89%) and nephrocalcinosis (11%) caused by metabolic disorders (62%), FHHNC (21%), and dRTA (17%)., Results: The mean age at discovery was 72.7 months. The underlying metabolic etiologies included hyperoxaluria (38%), cystinuria (32%), hypercalciuria (24%), and hyperuricosuria (6%). Genetic testing was carried out for 23 patients. Hyperoxaluria was typically treated medically (75%). However, the majority progressed to end-stage kidney disease (ESKD). Most children with cystinuria, hypercalciuria, and hyperuricosuria required medical and surgical intervention. Patients with FHHNC typically presented with nephrocalcinosis. Genetic testing revealed Claudin-16 mutations in 7 children. Patients often progressed to stage II-IV chronic kidney disease (61%) and ESKD (6%). Patients with dRTA typically presented with nephrocalcinosis (80%), as well as poor weight gain and failure to thrive (86%), and medical treatment included sodium bicarbonate and potassium replacement. Despite nephrocalcinosis progression, most patients had normal renal function (53%), although the remaining 47% progressed to chronic kidney disease (none reached ESKD)., Conclusion: Childhood nephrolithiasis is mainly related to metabolic disorders and is associated with poor renal outcomes. Nephrocalcinosis and nephrolithiasis have poor outcomes when associated with FHHNC, while nephrocalcinosis associated with dRTA has relatively good renal outcomes., (Copyright: © Saudi Medical Journal.)

The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Background: SARS-CoV-2 infection has a high mortality rate and continues to be a global threat, which warrants the identification of all mortality risk factors in critically ill patients., Methods: This is a retrospective multicenter cohort study conducted in five hospitals in the Kingdom of Saudi Arabia (KSA). We enrolled patients with confirmed SARS-COV-2 infection admitted to any of the intensive care units from the five hospitals between March 2020 and July 2020, corresponding to the peak of recorded COVID-19 cases in the KSA., Results: In total, 229 critically ill patients with confirmed SARS-CoV-2 infection were included in the study. The presenting symptoms and signs of patients who died during hospitalization were not significantly different from those observed among patients who survived. The baseline comorbidities that were significantly associated with in-hospital mortality were diabetes (62% vs. 48% among patients who died and survived ( p = 0.046)), underlying cardiac disease (38% vs. 19% ( p = 0.001)), and underlying kidney disease (32% vs. 12% ( p < 0.001))., Conclusion: In our cohort, the baseline comorbidities that were significantly associated with in-hospital mortality were diabetes, underlying cardiac disease, and underlying kidney disease. Additionally, the factors that independently influenced mortality among critically ill COVID-19 patients were high Activated Partial Thromboplastin Time (aPTT )and international normalization ratio (INR), acidosis, and high ferritin.

Advanced chronic kidney disease with mineral and bone disorder have a significant obstacles to control serum bone profile [serum intact parathyroid hormone (iPTH), calcium and phosphorus] which subsequently have major effect on optimal bone strength, final adult height, and cardiovascular health. A retrospective, observational study, including a total of 36 children with end-stage kidney disease (ESKD). Fourteen children who were prescribed cinacalcet had been compared with the remaining 22 children who were managed with standard care. We report the efficacy and safety of cinacalcet for treatment of refractory secondary hyperparathyroidism (SHPT) in children with ESKD. After 6 months of cinacalcet treatment, the mean level of iPTH serum level decreased by 56% from 202 pmol/L [95% confidence interval (CI): 150-253] to 88 pmol/L (95% CI: 41-136), compared to the change observed in the control group (P <0.001). None of our patients reported serious adverse effects or developed hypocalcemia. Cinacalcet could be an effective and safe alternative to treat severe SHPT in children with ESKD. Further long-term and large-scale studies are necessary to confirm its safety and efficacy., Competing Interests: None

Trichinellosis is a zoonosis results from eating raw or semi-cooked meat of infected animals. Medicinal plants have been used lately as alternatives and/or combined therapies to resolve some drawbacks of the current regimens. This work analyzed the effect of albendazole monotherapy on Trichinella spiralis experimental infection (group A), in comparison to P. granatum and amygdalin extracts +cobalamin (group B), plus its combination with albendazole (group C). The study revealed that the extracts alone or combined with albendazole had an inferior effect to albendazole monotherapy regarding number of adult worms (40.83 ±3.82, 18.67 ±1.86 and 16.83 ±2.32, respectively). However, their effect was more obvious in muscle phase combined with albendazole, achieving the lower number of larvae/mL tissue homogenate (22.33 ±3.27 in comparison to 39.67 ±2.58 achieved by albendazole monotherapy). The extracts exerted a significant immunomodulatory effect by reducing the local CD4+ expression in the intestine as well as in muscle phase (1.15 ±0.25 and 3.80 ±0.65 in comparison to 4.97 ±0.37 and 12.20 ±0.87 with albendazole monotherapy, respectively). So, these extracts improved the therapeutic efficacy of albendazole, specifically in muscle phase and counteracted the inflammatory reaction caused by albendazole monotherapy, thus extensively alleviating the resulting myositis.

Background: Dopamine D 2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D 2 agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D 2 receptor agonists in rats with alloxan-induced diabetes., Methods: Both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size., Results: Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method., Conclusions: The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues., (© 2021. The Author(s).)

The design of covalently linked [60]fullerene dimers has gained increased attention, as the linked electron donors or acceptors are in close proximity to the surface of the C 60 , providing a valuable approach to novel molecular electronic devices. Herein, new compounds involving C 60 dumbbells covalently connected by the π-conjugated system from azobenzene and diaryl ether linkers were synthesized following the bifunctional cycloaddition reactions to C 60 using microwave radiation. The structural identity of the fullerene dimers has been determined using spectroscopic techniques including Fourier transform infrared (FT-IR), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF), and NMR spectroscopy, and the photophysical and the electrochemical properties for the new dumbbells have been examined using UV-vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and square wave voltammetry. Both new dimers show electronic interaction with the fullerene cage and higher electron affinity than the pristine C 60 ., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Acute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19). The reported incidence of AKI, however, varies among studies. We aimed to evaluate the incidence of AKI and its association with mortality and morbidity in children infected with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission., Methods: This was a multicenter retrospective cohort study from three tertiary centers, which included children with confirmed COVID-19. All children were evaluated for AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging., Results: Of 89 children included, 19 (21 %) developed AKI (52.6 % stage I). A high renal angina index score was correlated with severity of AKI. Also, multisystem inflammatory syndrome in children (MIS-C) was increased in children with AKI compared to those with normal kidney function (15 % vs. 1.5 %). Patients with AKI had significantly more pediatric intensive care admissions (PICU) (32 % vs. 2.8 %, p < 0.001) and mortality (42 % vs. 0 %, p < 0.001). However, AKI was not associated with prolonged hospitalization (58 % vs. 40 %, p = 0.163) or development of MIS-C (10.5 % vs. 1.4 %, p = 0.051). No patient in the AKI group required renal replacement therapy. Residual renal impairment at discharge occurred in 9 % of patients. This was significantly influenced by the presence of comorbidities, hypotension, hypoxia, heart failure, acute respiratory distress, hypernatremia, abnormal liver profile, high C-reactive protein, and positive blood culture., Conclusions: AKI occurred in one-fifth of children with SARS-CoV-2 infection requiring hospital admission, with one-third of those requiring PICU. AKI was associated with increased morbidity and mortality, and residual renal impairment at time of discharge.

The genus capripoxvirus (CaPV), family Poxviridae , includes three virus species: goatpox virus (GPV), sheeppox virus (SPV) and lumpy skin disease virus (LSDV). CaPV causes disease outbreaks with consequent economic losses in Africa and the Middle East. LSDV has recently spread to Southeast Europe. As CaPVs share 96-97% genetic similarity along the length of the entire genome and are difficult to distinguish using serological assays, simple, reliable and fast methods for diagnosis and species differentiation are crucial in cases of disease outbreak. The present study aimed to develop a field-applicable CaPV differentiation method. Nanopore technology was used for whole genome sequencing. A local database of complete CaPV genomes and partial sequences of three genes (RPO30, P32 and GPCR) was established for offline Basic Local Alignment Search Tool (BLAST). Specificities of 98.04% in whole genome and 97.86% in RPO30 gene runs were obtained among the three virus species, while other databases were less specific. The total run time was shortened to approximately 2 h. Functionality of the developed procedure was proved by samples with high host background sequences. Reliable differentiation options for the quality and capacity of hardware, and sample quality of suspected cases, were derived from these findings. The whole workflow can be performed rapidly with a mobile suitcase laboratory and mini-computer, allowing application at the point-of-need with limited resource settings.

Background: The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus 2 infection, warranted attention for whether it has unique manifestations in children. Children tend to develop less severe disease with a small percentage present with clinical manifestations of paediatric multisystem inflammatory syndrome and have poor prognosis. We studied the characteristics of COVID-19 in children requiring hospitalisation in the Kingdom of Saudi Arabia and assessed the clinical presentation and the risk factors for mortality, morbidity, and paediatric intensive care (PICU) admission., Methods: We conducted a retrospective analysis of COVID-19 patients under 15 years hospitalised at three tertiary academic hospitals between 1 March and 30 June 2020., Results: Eighty-eight children were enrolled (>20% were infants). Seven (8%) were in critical condition and required PICU admission, and 4 (4.5%) died of which 3 met the full diagnostic criteria of multi-system inflammatory syndrome and had a high Paediatric Risk of Mortality (PRISM) score at the time of admission. The initial polymerase chain reaction (PCR) test result was positive for COVID-19 in most patients (97.7%), and the remaining two patients had positive result in the repeated confirmatory test. In a subset of patients (20 subjects), repeated PCR testing was performed until conversion to negative result, and the average duration for conversion was 8 (95% CI: 5.2-10.5) days Children requiring PICU admission presented with signs of respiratory distress, dehydration, and heart failure. Most had fever (71.4%) and tonsillitis; 61.4% were discharged within 7 days of hospitalisation. Risk factors for mortality included skin rash, hypotension, hypoxia, signs of heart failure, chest radiograph suggestive of acute respiratory distress syndrome, anaemia, leucocytosis, hypernatraemia, abnormal liver enzymes, and high troponin I, and risk factors for prolonged hospitalisation (>7 days) included the presence of comorbidities, leucopaenia, hyponatraemia, and elevated C-reactive protein., Conclusions: The majority of hospitalised children had a brief febrile illness and made a full recovery, but a minority had severe disease., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In March 2020, the SARS-CoV-2 virus outbreak was declared as a world pandemic by the World Health Organization (WHO). The only measures for controlling the outbreak are testing and isolation of infected cases. Molecular real-time polymerase chain reaction (PCR) assays are very sensitive but require highly equipped laboratories and well-trained personnel. In this study, a rapid point-of-need detection method was developed to detect the RNA-dependent RNA polymerase (RdRP), envelope protein (E), and nucleocapsid protein (N) genes of SARS-CoV-2 based on the reverse transcription recombinase polymerase amplification (RT-RPA) assay. RdRP, E, and N RT-RPA assays required approximately 15 min to amplify 2, 15, and 15 RNA molecules of molecular standard/reaction, respectively. RdRP and E RT-RPA assays detected SARS-CoV-1 and 2 genomic RNA, whereas the N RT-RPA assay identified only SARS-CoV-2 RNA. All established assays did not cross-react with nucleic acids of other respiratory pathogens. The RT-RPA assay's clinical sensitivity and specificity in comparison to real-time RT-PCR ( n = 36) were 94 and 100% for RdRP; 65 and 77% for E; and 83 and 94% for the N RT-RPA assay. The assays were deployed to the field, where the RdRP RT-RPA assays confirmed to produce the most accurate results in three different laboratories in Africa ( n = 89). The RPA assays were run in a mobile suitcase laboratory to facilitate the deployment at point of need. The assays can contribute to speed up the control measures as well as assist in the detection of COVID-19 cases in low-resource settings.

Introduction: There are scarce data comparing different mechanical valves in the aortic position. The objective of this study was to compare the early hemodynamic changes after aortic valve replacement between ATS, Bicarbon, and On-X mechanical valves., Methods: We included 99 patients who underwent aortic valve replacement with mechanical valves between 2017 and 2019. Three types of mechanical valves were used, On-X valve (n=45), ATS AP360 (n=32), and Bicarbon (n=22). The mean prosthetic valve gradient was measured postoperatively and after six months., Results: Preoperative data were comparable between groups, and there were no differences in preoperative echocardiographic data. Pre-discharge echocardiography showed no difference between groups in the ejection fraction (P=0.748), end-systolic (P=0.764) and end-diastolic (P=0.723) diameters, left ventricular mass index (P=0.348), aortic prosthetic mean pressure gradient (P=0.454), and indexed aortic prosthetic orifice area (P=0.576). There was no difference in the postoperative aortic prosthetic mean pressure gradient between groups when stratified by valve size. The changes in the aortic prosthetic mean pressure gradient of the intraoperative period, at pre-discharge, and at six months were comparable between the three prostheses (P=0.08). Multivariable regression analysis revealed that female gender (beta coefficient -0.242, P=0.027), body surface area (beta coefficient 0.334, P<0.001), and aortic prosthetic size (beta coefficient -0.547, P<0.001), but not the prosthesis type, were independent predictors of postoperative aortic prosthetic mean pressure gradient., Conclusion: The three bileaflet mechanical aortic prostheses (On-X, Bicarbon, and ATS) provide satisfactory early hemodynamics, which are comparable between the three valve types and among different valve sizes.