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Background: Chromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty., Results: We identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene., Conclusion: This report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies., (© 2024. The Author(s).)

Chitosan (CS) is a biopolymer that offers a wide range in biomedical applications due to its biocompatibility, biodegradability, low toxicity and antimicrobial activity. Syringaldehyde (1) is a naturally occurring organic compound characterized by its use in multiple fields such as pharmaceuticals, food, cosmetics, textiles and biological applications. Herein, development of chitosan derivative with physicochemical and anticancer properties via Schiff base formation from the reaction of chitosan with sustainable eco-friendly syringaldehyde yielded the (CS-1) derivative. Moreover, in the presence of polyethylene glycol diglycidyl ether (PEGDGE) or sodium tripolyphosphate (TPP) as crosslinkers gave chitosan derivatives (CS-2) and (CS-3NPs) respectively. The chemical structures of the new chitosan derivatives were confirmed using different tools. (CS-3NPs) nanoparticle showed improvement in crystallinity, and (CS-2) derivative revealed the highest thermal stability compared to virgin chitosan. The cytotoxicity activity of chitosan and its derivatives were evaluated against HeLa (human cervical carcinoma) and HEp-2 (Human Larynx carcinoma) cell lines. The highest cytotoxicity activity was exhibited by (CS-3NPs) compared to virgin chitosan against HeLa cell growth inhibition and apoptosis of 90.38 ± 1.46% and 30.3% respectively and IC 50 of 108.01 ± 3.94 µg/ml. From the above results, it can be concluded that chitosan nanoparticle (CS-3NPs) has good therapeutic value as a potential antitumor agent against the HeLa cancer cell line., (© 2024. The Author(s).)

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4 H -chromene-3-carboxylates 7a - g , 8 , and 11a - e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, h CAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.

Background: Fungi are a readily available source of naturally generated colored compounds. These compounds might be used as radiosensitizers for treating cancer cells., Methods: Aspergillus nidulans was examined for its color-producing ability in Potato dextrose agar (PDA) broth medium. The pigment was characterized by Ultraviolet (UV) spectrophotometer and Gas Chromatography Mass Spectrometry (GC/MS). Pigment extracts from A. nidulans were studied for their cytotoxic effects on the growth of human larynx carcinoma cell line (HEp-2) with or without exposure to γ-radiation at three different doses (5, 10, and 15 Gy). A. nidulans pigment cytotoxic activity was tested against normal Vero cells. Cell apoptosis was studied using flow cytometry. Gene expression of P53, Caspase 3 and Bcl-2 were quantified., Results: Ultraviolet spectrum and GC/MS revealed the ability of Aspergillus nidulans to produce Rhodopin pigment. HEp-2 cells treated with A. nidulans pigment only give IC 50 about 208 µg/ml. In contrast, when treated with the pigment +10 Gy γ-radiation, it give about 115 µg/ml. However, for normal cells, lower cytotoxic activity was detected. Treatment with pigment (208 g/mL) caused about 50% ± 1.0 total apoptosis level and gene expression of P53: 2.3 fold and Caspase 3: 1.84 fold in respect to untreated HEp-2), while Bcl-2 was decreased (Bcl-2: 0.63 fold in respect to untreated HEp-2). Furthermore, treated with pigment (115 µg/mL) + 10Gy caused about 47.41% ± 1.7 total apoptosis level and P53: 2.53 fold and Caspase 3: 2.0 fold in respect to untreated HEp-2, while Bcl-2 was downregulated (Bcl-2: 0.61 fold in respect to untreated HEp-2)., Conclusion: This study concluded that the anti-cancer activity of Aspergillus nidulans pigment was enhanced by ionizing radiation at 10 Gy, as well as its low cytotoxic activity against normal Vero cells., (© 2023. BioMed Central Ltd., part of Springer Nature.)

COVID-19, the novel coronavirus, has posed a major threat to low- and middle-income countries (LMICs) due to inadequate health infrastructure and human resources. Ethiopia, a low-income country with the second largest population in Africa, has coordinated a strategic response, leveraging existing infrastructure and health systems and mobilizing public health professionals and specialist expert physicians for a multifaceted, unified government approach and adaptive response. Resource limitations, particularly in critical care, have still posed challenges, but the public health and clinical interventions thus far have prevented the catastrophic toll that many predicted. As the pandemic continues, Ethiopia expects to use a triple care model integrated at all levels, consisting of COVID-19 care, isolation care for suspected cases, and essential health services, and urges intensified non-pharmaceutical interventions alongside equitable global vaccine distribution as the ultimate answers to pandemic control. This paper draws on existing data, national planning and guidelines, and expertise from health leadership to describe this response in hopes of providing an example of how future large-scale health challenges might be faced in LMICs, using Ethiopia's successes and challenges in facing the pandemic., Competing Interests: Conflicts of interest: none declared., (© 2022 The Union.)

Introduction: Evidence on the interplay between HIV and COVID-19 is not entirely consistent., Methods: A retrospective cohort study was conducted on the medical records of patients who had a positive RT-PCR for COVID-19 and were admitted to Eka Kotebe General Hospital between March 2020 and October 2021., Results: A total of 427 patients, including 108 people living with HIV/AIDS (PLWH) and 319 people without HIV/AIDS, were included in the study. The median age of PLWH and people without HIV was 49.5 years (interquartile range 40-59 years) and 48 years (interquartile range 32-65 years), respectively. Of these patients, 258 (60.4%) were male and 169 (39.6%) were female. There were significant differences between PLWH and people without HIV in terms of age, tuberculosis, pregnancy, chronic liver disease, complications, shock, white blood cell count, and end outcome (alive or dead). There was no association between HIV status and the need for oxygen, intensive care unit admission, or disease severity. After adjusting for other variables, mortality was significantly higher among PLWH (adjusted odds ratio 2.25, 95% confidence interval 1.11-5.56; P  = 0.023)., Conclusions: PLWH with COVID-19 had a higher rate of in-hospital mortality than people without HIV, although no association was found between HIV status and the requirement for intensive care unit admission, mechanical ventilation, oxygen support, or the severity of the disease at the time of admission., (© 2022 The Authors.)

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils' anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC 50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 μg/mL, respectively. In contrast, at 20 MPa, the IC 50 values were about 2.33, 6.59, and 19.0 μg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 μg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC 50 14.4 μg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.

Acetaminophen, also known as N-acetyl-para-aminophenol (NAPAP), is a traditional antipyretic and analgesic that is used extensively around the world to treat colds and fevers. However, a NAPAP excess causes rapid, severe liver and kidney damage. The goal of the study was to examine the protective effects and determine the mechanisms of action of MPHE, hesperidin, and quercetin in NAPAP-induced hepatorenal damage in Wistar rats. Male Wistar rats received a 0.5 g/kg oral supplement of NAPAP every other day for a period of four weeks. During the same period of NAPAP supplementation, MPHE (50 mg/kg), quercetin (20 mg/kg), and hesperidin (20 mg/kg) were administered to rats receiving NAPAP. MPHE, quercetin, and hesperidin treatments significantly improved liver function in NAPAP-supplemented rats. The high serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, and γ -glutamyl transferase as well as total bilirubin were significantly reduced, while the levels of suppressed serum albumin were significantly increased, demonstrating this improvement. Treatments utilizing these natural substances significantly enhanced kidney function as seen by a considerable decline in the increased blood levels of urea, uric acid, and creatinine. Additionally, the injection of MPHE, hesperidin, and quercetin resulted in a decrease in the quantity of lipid peroxides while increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase in the liver and kidneys. The treatments markedly abated the NAPAP-induced liver and kidney histological perturbations and reduced the NAPAP-induced serum tumor necrosis factor- α level and liver and kidney proapoptotic protein 53 and caspase 3 expressions. Otherwise, serum interleukin-4 level significantly increased by treatments. The MPHE, hesperidin, and quercetin treatments resulted in marked decrease in liver and kidney histopathological scores including inflammation, necrosis, apoptosis, and congestion. In conclusion, the MPHE, quercetin, and hesperidin may induce hepatonephropreventive impacts in NAPAP-supplemented rats via enhancing the antioxidant defense system, anti-inflammatory activity, and antiapoptotic action., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Doaa Nor Eldin et al.)

Data from much of Africa are still scarce on the clinical characteristics, outcomes of treatment, and factors associated with disease severity and mortality of COVID-19. A cross-sectional study was conducted at Eka Kotebe General Hospital, Ethiopia's first COVID-19 treatment center. All consecutive symptomatic SARS CoV-2 RT-PCR positive individuals, aged 18 and older, admitted to the hospital between March 13 and September 16, 2020, were included. Of the total 463 cases, 319 (68.9%) were male. The median age was 45 years (interquartile range 32-62). The most common three symptoms were cough (69%), shortness of breath (SOB; 44%), and fatigue (37%). Hypertension was the most prevalent comorbidity, followed by diabetes mellitus. The age groups 40 to 59 and ≥ 60 were more likely to have severe disease compared with those < 40 years of age (adjusted odds ratio [aOR] = 3.45, 95% confidence interval [CI]: 1.88-6.31 and aOR = 3.46, 95% CI: 1.91-6.90, respectively). Other factors associated with disease severity included the presence of any malignancy (aOR = 4.64, 95% CI: 1.32-16.33) and SOB (aOR = 3.83, 95% CI: 2.35-6.25). The age group ≥ 60 was significantly associated with greater in-hospital mortality compared with those < 40 years. In addition, the presence of any malignancy, SOB, and vomiting were associated with higher odds of mortality. In Ethiopia, most COVID-19 patients were male and presented with cough, SOB, and fatigue. Older age, any malignancy, and SOB were associated with disease severity; these factors, in addition to vomiting, also predicted mortality.

Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH) worldwide, but the prevalence and risk factors for schistosomiasis-associated PAH (SchPAH) development are not well understood. Schistosomiasis-associated hepatosplenic disease (SchHSD) is thought to be a major risk factor for PAH development. Herein, we describe our plans for prospectively screening SchHSD subjects for clinical evidence of PAH at two major academic medical centers and national referral hospitals in Addis Ababa, Ethiopia and Lusaka, Zambia. The screening study will primarily be conducted by echocardiography, in addition to clinical assessments. Plasma samples will be drawn and banked for subsequent analysis based on preclinical animal model rationale. If successful, this study will demonstrate feasibility of conducting prospective cohort studies of SchPAH screening in schistosomiasis-endemic regions of Africa, and provide initial data on clinic-based disease prevalence and potential mechanistic biomarkers underlying disease pathogenesis., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Hydroxyapatite nanoparticles (HAn) have been produced as biomaterial from biowaste, especially snail shells ( Atactodea glabrata) . It is critical to recycle the waste product in a biomedical application to overcome antibiotic resistance as well as biocompatibility with normal tissues. Moreover, EDX, TEM, and FT-IR analyses have been used to characterize snail shells and HAn. The particle size of HAn is about 15.22 nm. Furthermore, higher inhibitory activity was observed from HAn than the reference compounds against all tested organisms. The synthesized HAn has shown the lowest MIC values of about 7.8, 0.97, 3.9, 0.97, and 25 µg/mL for S. aureus , B. subtilis , K. pneumonia , C. albicans , and E. coli , respectively. In addition, the HAn displayed potent antibiofilm against S. aureus and B. subtilis . According to the MTT, snail shell and HAn had a minor influence on the viability of HFS-4 cells. Consequently, it could be concluded that some components of waste, such as snail shells, have economic value and can be recycled as a source of CaO to produce HAn, which is a promising candidate material for biomedical applications.

Aim: This study aims to prepare a nanocomposite (HPMC/5-FL@GO) from hydroxypropyl methylcellulose (HPMC) and graphene oxide (GO) as biocompatible materials. The nanocomposite enhances the drug activity of immobilized 5-fluorouracil (5-FU), decreasing the side effect of long-run treatment protocols with highly efficient drug-drug activity., Method and Results: Different samples were characterized by ATR-FTIR spectroscopy, X-ray diffraction, scanning electron microscopy coupled with energy dispersive X-ray analysis, transmission electron microscopy, thermogravimetric analysis, and dynamic light scattering along with cytotoxicity and anticancer study. A homogenous and compatible nanocomposite structure with a homogenous drug distribution was confirmed. Furthermore, the prepared nanocomposite has a low cytotoxicity effect against normal Vero cell lines compared with 5-FU. The antitumor activities of the same nanocomposite (20.4 and 74.3 μg mL -1 on A549 and HepG-2) were lower than that of 5-FU (54.1 and 103 μg mL -1 on A549 and HepG-2)., Conclusion and Implications: According to the attained results, the HPMC/5-FL@GO can apply in a biomedical application such as cancer therapy with the unique biocompatible to human cells., (© 2021 Wiley-VCH GmbH.)

The advent of the Internet of Things (IoT) has enabled millions of potential new uses for consumers and businesses. However, with these new uses emerge some of the more pronounced risks in the connected object domain. Finite fields play a crucial role in many public-key cryptographic algorithms (PKCs), which are used extensively for the security and privacy of IoT devices, consumer electronic equipment, and software systems. Given that inversion is the most sensitive and costly finite field arithmetic operation in PKCs, this paper proposes a new, fast, constant-time inverter over prime fields Fp based on the traditional Binary Extended Euclidean (BEE) algorithm. A modified BEE algorithm (MBEEA) resistant to simple power analysis attacks (SPA) is presented, and the design performance area-delay over Fp is explored. Furthermore, the BEE algorithm, modular addition, and subtraction are revisited to optimize and balance the MBEEA signal flow and resource utilization efficiency. The proposed MBEEA architecture was implemented and tested on Xilinx FPGA Virtex #5, #6, and #7 devices. Our implementation over Fp (length of p = 256 bits) with 2035 slices achieved one modular inversion in only 1.12 μs on Virtex-7. Finally, we conducted a thorough comparison and performance analysis to demonstrate that the proposed design outperforms the competing designs, i.e., has a lower area-delay product (ADP) than the reported inverters.

Background: Capparis spinosa grows in Asian and Mediterranean desert areas. Different parts of Capparis spinosa, including flowers, have been used in various folk medicine applications., Objective: This study aims to evaluate the anti-arthritic potential of ethanolic extract of Egyptian Capparis spinosa flowers in a rat model of rheumatoid arthritis. Moreover, analysis of Capparis spinosa extract was performed using LC-qTOF-MS/MS., Methods: Animals were split into six groups: negative control group, induced arthritic animals, arthritic rats receiving 7, 14 and 28 mg/kg of Capparis spinosa extract, respectively, in three groups to detect the optimum dose, and the induced group receiving a standard drug. The arthritic score was checked daily for 15 days after induction. After animals were sacrificed, their joints and muscles were subjected to microscopic and ultra-structure examinations. Ex vivo culturing of osteoclasts was performed. Cytokine levels were measured in all examined groups., Results: The results revealed 7 mg/kg of Capparis spinosa extract as the optimal dose, which decreased inflammation signs through controlling chondrocytes, osteoclasts, and levels of inflammatory mediators., Conclusion: LC-Mass analysis revealed Capparis spinosa extract to contain a mixture of flavonol glycosides, flavan-3-ols and hydroxycinnamic acid derivatives, which may provide beneficial multifunction in regulating arthritic symptoms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Selenium is a fundamental trace element of the living system. Microorganisms play a crucial role in the selenium cycle, both in the environment and in life. Biogenic selenium nanoparticles have shown promising prospects for use in medicine as an antioxidant and anticancer agent. In this study, SeNPs were biosynthesized by Penicillium citrinum . The spore suspension which was previously prepared was exposed to different doses of gamma radiation (10, 20, 30, 50, and 60 Gy). SeNPs were then produced by an irradiated P citrinum . UV spectroscopy, transmission electron microscopy, X-ray diffraction, and GSH content were assayed to evaluate the probability of P citrinum synthesizing SeNPs. In conclusion, irradiation of P citrinum by gamma ray enhances the mycosynthesis of SeNPs., Competing Interests: Declaration of Conflicting 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) 2021.)

Chronic diseases and viral infections have threatened human life over the ages and constitute the main reason for increasing death globally. The rising burden of these diseases extends to negatively affecting the economy and trading globally, as well as daily life, which requires inexpensive, novel, and safe therapeutics. Therefore, scientists have paid close attention to probiotics as safe remedies to combat these morbidities owing to their health benefits and biotherapeutic effects. Probiotics have been broadly adopted as functional foods, nutraceuticals, and food supplements to improve human health and prevent some morbidity. Intriguingly, recent research indicates that probiotics are a promising solution for treating and prophylactic against certain dangerous diseases. Probiotics could also be associated with their essential role in animating the immune system to fight COVID-19 infection. This comprehensive review concentrates on the newest literature on probiotics and their metabolism in treating life-threatening diseases, including immune disorders, pathogens, inflammatory and allergic diseases, cancer, cardiovascular disease, gastrointestinal dysfunctions, and COVID-19 infection. The recent information in this report will particularly furnish a platform for emerging novel probiotics-based therapeutics as cheap and safe, encouraging researchers and stakeholders to develop innovative treatments based on probiotics to prevent and treat chronic and viral diseases.

Materials and Methods: In this retrospective cross-sectional single center study, records of patients with esophageal strictures presented to the pediatric department, Salmaniya Medical Complex, Bahrain, in the period between 1995 and 2019 were reviewed. Demographic data, indications of endoscopic dilatations, the procedure success rate, and possible complications were assessed., Results: Forty-six children were found to have esophageal strictures. Twenty-five (54.3%) patients were males. Most patients presented during infancy (86.5%, 32/37 patients). Twenty-six (56.5%) patients required 88 dilatation sessions, while the remaining 20 (43.5%) patients did not require dilatations. The median number of dilatation sessions per patient was three (interquartile range = 2-5). Savary-Gilliard bougienages were the main dilators used (80.8%, 21/26 patients). Anastomotic stricture (post esophageal atresia/tracheoesophageal fistula repair) was the main cause of esophageal strictures and was found in 35 (76.1%) patients. Patients with nonanastomotic strictures had more frequent dilatations compared to those with anastomotic strictures ( P = 0.007). The procedure success rate was 98.8%. Yet, it was operator dependent ( P = 0.047). Complete response to dilatation was found in 18 (69.2%) patients, satisfactory in seven (26.9%), and an inadequate response in one (3.9%). Those with satisfactory responses still require ongoing dilatations based on their symptoms and radiological and endoscopic findings. No perforation or mortality was reported. Patients with dilatations had more recurrent hospitalization ( P < 0.0001), more dysphagia ( P = 0.001), but shorter hospital stay ( P = 0.046) compared to those without dilatations. Surgical intervention was required in one patient with caustic strictures. The median follow-up period was six years (interquartile range = 2.25-9.0)., Conclusions: Endoscopic esophageal dilatation in children with esophageal strictures is effective and safe. Yet, it was operator dependent. Nonanastomotic strictures require more dilatations compared to anastomotic strictures. Findings of this study are comparable to those reported worldwide., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Hasan M. A. Isa et al.)

In this study, Egyptian beebread (EBB) was investigated for its nutritive value, chemical composition, antioxidant properties, antimicrobial and antitumor activities. Results indicated that EBB was a good source of protein (23.58 ± 0.183 g/100 g BB), total free sugar (20.266 ± 0.930) and potassium (290.202 ± 2.645 mg/100 g). Additionally, 14 fatty acids were identified in EBB, wherein polyunsaturated and monounsaturated fatty acids represented 51.06% ± 0.09% and 9.86% ± 0.01%, respectively. The EBB extract exhibited almost 400% better antiradical activity than BHT, with IC 50 of EBB extract being 10.7 µg/mL compared to 39.5 µg/mL for BHT. EBB exhibited higher inhibitory activity than the reference compound against Staphylococcus aureus and Escherichia coli , followed by Bacillus subtilis. No inhibitory activity was observed against Aspergillus Niger . Additionally, the highest inhibitory activity was recorded against Caco-2 cells, followed by PC3 and HepG-2 cancer cell lines with IC 50 values 262, 314 and 386 μg/mL, respectively. These findings establish the potential of EBB as an antioxidant, antimicrobial and antitumor agent, with possible applications as natural food supplements and natural preservatives.

New studies of COVID-19 are constantly updating best practices in clinical care. However, research mainly originates in resource-rich settings in high-income countries. Often, it is impractical to apply recommendations based on these investigations to resource-constrained settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for tracheostomy, discharge, and rehabilitation measures in hospitalized patients recovering from severe COVID-19 in LMICs. We recommend that tracheostomy be performed in a negative pressure room or negative pressure operating room, if possible, and otherwise in a single room with a closed door. We recommend using the technique that is most familiar to the institution and that can be conducted most safely. We recommend using fit-tested enhanced personal protection equipment, with the fewest people required, and incorporating strategies to minimize aerosolization of the virus. For recovering patients, we suggest following local, regional, or national hospital discharge guidelines. If these are lacking, we suggest deisolation and hospital discharge using symptom-based criteria, rather than with testing. We likewise suggest taking into consideration the capability of primary caregivers to provide the necessary care to meet the psychological, physical, and neurocognitive needs of the patient.

New studies of COVID-19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non-COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of "enhanced" or "intermediate" prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D-dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D-dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

Pulmonary arterial hypertension (PAH) is a disease of the lung blood vessels that results in right heart failure. PAH is thought to occur in about 5% to 10% of patients with hepatosplenic schistosomiasis, particularly due to S. mansoni . The lung blood vessel injury may result from a combination of embolization of eggs through portocaval shunts into the lungs causing localized Type 2 inflammatory response and vessel remodeling, triggering of autonomous pathology that becomes independent of the antigen, and high cardiac output as seen in portopulmonary hypertension. The condition is likely underdiagnosed as there is little systematic screening, and risk factors for developing PAH are not known. Screening is done by echocardiography, and formal diagnosis requires invasive right heart catheterization. Patients with Schistosoma -associated PAH show reduced functional capacity and can be treated with pulmonary vasodilators, which improves symptoms and may improve survival. There are animal models of this disease that might help in understanding disease pathogenesis and identify novel targets to screen and treatment. Pathogenic mechanisms include Type 2 immunity and activation and signaling in the TGF-β pathway. There are still major uncertainties regarding Schistosoma -associated PAH development, course and treatment., 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 © 2020 Sibomana, Campeche, Carvalho-Filho, Correa, Duani, Pacheco Guimaraes, Hilton, Kassa, Kumar, Lee, Loureiro, Mazimba, Mickael, Oliveira, Ota-Arakaki, Rezende, Silva, Sinkala, Ahmed and Graham.)

As a continuation for our previous work, a novel set of N -alkylindole-isatin conjugates ( 7 , 8a-c , 9 and 10a-e ) is here designed and synthesised with the prime aim to develop more efficient isatin-based antitumor candidates. Utilising the SAR outputs from the previous study, our design here is based on appending four alkyl groups with different length (ethyl and n-propyl), bulkiness (iso-propyl) and unsaturation (allyl) on N -1 of indole motif, with subsequent conjugation with different N -unsubstituted isatin moieties to furnish the target conjugates. As planned, the adopted strategy achieved a substantial improvement in the growth inhibitory profile for the target conjugates in comparison to the reported lead VI . The best results were obtained with N -propylindole -5-methylisatin hybrid 8a which displayed broad spectrum anti-proliferative action with efficient sub-panel GI 50 (MG-MID) range from 1.33 to 4.23 µM, and promising full-panel GI 50 (MG-MID) equals 3.10 µM, at the NCI five-dose assay. Also, hybrid 8a was able to provoke cell cycle disturbance and apoptosis in breast T-47D cells as evidenced by the DNA flow cytometry and Annexin V-FITC/PI assays. Furthermore, hybrid 8a exhibited good inhibitory action against cell cycle regulator CDK2 protein kinase and the anti-apoptotic Bcl-2 protein (IC 50 = 0.85 ± 0.03 and 0.46 ± 0.02 µM, respectively). Interestingly, molecular docking for hybrid 8a in CDK2 and Bcl-2 active sites unveiled that N -propyl group is involved in significant hydrophobic interactions. Taken together, the results suggested conjugate 8a as a promising lead for further development and optimisation as an efficient antitumor drug.

Peste des petits ruminants (PPR) is endemic to Sudan. It is considered as a priority disease in the list of transboundary animal diseases (TADs). The aim of this study was to assess the reliability of the detection of PPR antibodies by a competitive enzyme-linked immunosorbent assay (cELISA) in naturally infected or vaccinated sheep. Sera were collected from 3,186 sheep from flocks located in six states of Sudan and additionally 100 sheep were vaccinated with a PPR homologous vaccine (produced locally) in a quarantine station. The percentages of PPR antibody-positive sera from the field varied between 72% and 100%, according to state. All sheep vaccinated in the quarantine station were PPR-seropositive. This study shows, first, that the percentages of PPR-seropositive animals were all very high, whether naturally infected or vaccinated. It also shows the reliability of the cELISA test used in this study.

Despite the advantages of bacterial cellulose (BC) over traditional cellulose, its low yield and little bioactivity makes a limitation to be used in an industrial scale. This paper was mainly dual aimed to increase the BC yield using a nanobioactive glass (NBG), and in situ synthesize BC/NBG bioactive nanocomposites by a novel and simple green method. Accordingly, the composites were prepared via in situ fermentation approach by incorporation of NBG particles into BC producing culture medium. The effect of NBG addition on the production process of cellulose, biocompatibility, bioactivity and antimicrobial activity were investigated. The results showed that NBG was enhanced and increased the BC yield and this has been achieved by maintaining these NBG on the pH value of the culture medium during the fermentation period. Moreover, it was effectively improved biocompatibility and antimicrobial properties of BC. This study evidenced that BC/NBG composite can be expected to be widely applied in biomedical industries such as bone regeneration and wound healing with the unique of being not harmful to humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

N-Acetyl-p-aminophenol (APAP) or acetaminophen is the most common drug ingredient worldwide. It is found in more than 600 different over-the-counter and prescription medicines. Its long-term and overdose use is highly toxic and may result in liver injury. Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of the navel orange peel hydroethanolic extract, naringin, and naringenin in APAP-induced hepatotoxicity in male Wistar rats. APAP was administered to male Wistar rats at a dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with the navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.), and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with the peel extract, naringin, and naringenin produced a significant decrease in the elevated serum AST, ALT, ALP, LDH, and GGT activities as well as total bilirubin and TNF- α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver lipid peroxidation and enhanced the liver GSH content and SOD, GST, and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the liver LPO, GSH content, and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic proapoptotic mediators p53, Bax, and caspase-3 and significantly upregulated the suppressed antiapoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver histopathological deteriorations that include hepatocyte steatosis, cytoplasmic vacuolization, hydropic degeneration, and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells' infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin, and naringenin may exert their hepatopreventive effects in APAP-administered rats via enhancement of the antioxidant defense system and suppression of inflammation and apoptosis.

Herein we present the design, synthesis, and biological evaluation of three different series of novel sulfonamides (3a-f, 6a-f and 9a-f) incorporating substituted indolin-2-one moieties (as tails) linked to benzenesulfonamide (as zinc anchoring moieties) through aminoethyl or (4-oxothiazolidin-2-ylidene)aminoethyl linkers. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IV and VII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with K I s in the range of 42-8550.9 nM, hCA II in the range of 5.9-761 nM; hCA IV in the range of 4.0-2069.5 nM, whereas hCA VII in the range of 13.2-694 nM. Molecular docking studies were carried out for some of the tested compounds within the hCA II active site, allowed us to rationalize the obtained inhibition results., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The present study aims to assess the toxic effect of latex and ethanolic leaf extract of Calotropis procera ( C. procera ), in comparison to abamectin, on serum biomarkers of function and histological integrity of heart and testis in male albino rats. To achieve this aim, the albino rats were separately administered 1/20 and 1/10 of LD 50 of C. procera latex, ethanolic C. procera leaf extract and abamectin respectively by oral gavage for 4 and 8 weeks. C. procera latex and leaf extract as well as abamectin markedly elevated the activities of serum CK-MB, AST and LDH at the two tested periods in a dose dependent manner. Lipid peroxidation was significantly increased while GSH level and GPx, GST and SOD activities were significantly depleted in heart and testis of all treated rats. All treatments also induced a marked increase in serum TNF-α and decrease in serum IL-4, testosterone, FSH and LH levels in a dose dependent manner. The latex seemed to be more effective in deteriorating the testicular function and sex hormones' levels while the ethanolic leaf extract produced more deleterious effects on oxidative stress and antioxidant defense system in both heart and testis. The normal histological architecture and integrity of the heart and testis were perturbed after treatments and the severity of lesions, which include odema, inflammatory cell infiltration, necrosis and degeneration, is dose and time dependent. In conclusion, the findings of this study indicated that C. procera latex and ethanolic extract of leaves could induce marked toxicity in heart and testis and these toxic effects may be more or less similar to those of abamectin. The cardiotoxicity and testicular toxicity may be mediated via stimulation of inflammation, increased oxidative stress and suppression of antioxidant defense system.