Evaluation of masticatory performance and patient satisfaction for conventional and 3D-printed implant overdentures: a randomized crossover study.

BACKGROUND: This crossover clinical study aimed to evaluate and compare masticatory performance and patient satisfaction for patients rehabilitated with conventional heat-cured acrylic resin and 3D-printed mandibular implant overdentures retained with bar attachment. MATERIALS AND METHODS: Sixteen completely edentulous healthy participants received new conventional dentures. In the mandible, four interforaminal implants were inserted. Following the stage of osseointegration, the bar was constructed in a trapezoidal configuration. Each patient randomly received the following overdentures using a crossover design: (1) conventional heat-cured acrylic resin overdenture and (2) 3D-printed overdenture (developed by scanning of mandibular conventional overdenture). The masticatory performance was assessed by conducting a two-colour mixing ability test at 5, 10, 20, 30, and 50 masticatory cycles. Moreover, the McGill Denture Satisfaction Questionnaire (MDSQ) was employed to assess patient satisfaction. Evaluation was performed after 3 months of using each overdenture. Paired sample t tests were used to compare the masticatory performance and MDSQ scores of patients for both prostheses. RESULTS: No significant difference in masticatory performance was reported between the two types of overdentures. Regarding patient satisfaction, only the esthetic aspect was significantly better for conventionally processed overdentures than for printed overdentures. Insignificant differences were observed regarding other MDSQ items between the two overdentures. CONCLUSION: Within this clinical study, 3D-printed implant overdentures showed promising results in terms of chewing efficiency and patient satisfaction compared to conventionally fabricated implant overdentures. TRIAL REGISTRATION: Retrospectively registered at www. CLINICALTRIALS: gov : NCT06148727.(28/11/2023).

Mesenteric vein thrombosis: A case report.

INTRODUCTION: The most frequent location of thrombosis development in acute mesenteric venous thrombosis is the superior mesenteric vein. It is an uncommon but potentially fatal condition. Patients with underlying medical conditions that interfere with the Virchow Triad hypercoagulability, stasis, and endothelial injury are more likely to experience it. PRESENTATION: A 37-year-old female reported to our emergency department with a 5-day history of severe abdominal discomfort, vomiting, and constipation, as well as two episodes of bleeding per rectum. The patient had a clean medical history, no HTN, no diabetes, no chronic medication, no history of contraceptive pill use or non-steroid anti-inflammatory drug use, no history of chronic disease or operation. Patient was directly transferred to the intensive care unit for additional evaluation and preoperative stabilization. DISCUSSION: A patient with acute mesenteric venous thrombosis and possible intestinal damage is the case we've presented. Upon presentation patient was unstable, we assessed her condition and transferred to the intensive care unit for stabilization and pre-operative preparation. She didn't respond to conservative management and we had to operate, we highly emphasize how crucial it is for early intervention in these type of conditions. Acute mesenteric venous thrombosis is a complicated case due to its nonspecific symptoms, it requires a multidisciplinary team approach between internal medicine and surgical team to plan for the most appropriate treatment strategy suitable for each patient as all options are associated with significant risks. Multiple options are available for the management of mesenteric venous thrombosis. In patients with peritoneal signs to suggestive bowel infarction or perforation or those who failed to progress with conservative management, operative intervention may be necessary. Other options include anticoagulation therapy, local or systemic thrombolysis, interventional or surgical thrombectomy. CONCLUSION: Acute mesenteric venous thrombosis is a complex situation that calls for a multidisciplinary team approach between the surgical and internal medicine departments to determine the best course of action for each patient, as there are major risks involved with each alternative. If peritonism is present, it is preferable to assess and resuscitate as soon as possible and to proceed with surgery.

Accuracy of Modern and Traditional Intraocular Lens Power Calculation Formulas in Pediatric Cataract Surgery.

Purpose: To compare the accuracy of modern intraocular lens (IOL) power calculation formulas with that of older formulas, such as SRK/T and Hoffer Q, in pediatric cataract surgery. Methods: This retrospective study included 100 eyes of 100 children who underwent routine cataract surgery with primary IOL implantation in a bag. This study used four IOLMaster 700 integrated formulas: SRK/T, Hoffer Q, Haigis, and Barrett Universal II (BUII). In addition, the following formulas were used: EVO 2.0, Hill RBF 3.0, Hoffer QST, Kane, and PEARL DGS, which are available online. Results: There was a statistically significant difference between SRK/T and most other formulas, except for Hoffer Q, Hoffer QST, and BUII (p < 0.05). SRK/T yielded the lowest median absolute error (MedAE) of 0.63 D. This was followed by the BUII (0.66 D), Hoffer Q, and Hoffer QST (0.68 D). SRK/T also yielded the highest percentage of cases within ± 0.50 D (43% of the cases). For patients aged 2 to 5 years, SRK/T formula yielded statistically significantly better results than all other included formulas (p < 0.05) with MedAE = 0.44 D, 58.33% and 87.50% of the cases were within ± 0.50 D and ± 1.0 D of intended refraction, respectively. Conclusion: The SRK/T formula showed the best IOL power calculation results in pediatric cataract surgery, followed by BUII, Hoffer Q, and Hoffer QST. In children aged 2-5 years, the SRK/T formula outperformed all other formulas, followed by the BUII and Hoffer QST formulas. In children older than 5 years, there was no statistically significant difference between the different formulas (p > 0.05); Hoffer Q and SRK/T showed slightly better MedAE in this age group (5-10 years).

Empowerment and social inclusion through Para sports: a qualitative study on women with physical impairments in Saudi Arabia.

Background: Participation in sports represents a potent means of empowerment and social inclusion. Nevertheless, women with physical impairments encounter specific challenges in accessing Para sports. The main aim of this study is to present the experiential participation and achievements in sports of women with physical impairments in Saudi Arabia. Methods: Twenty women athletes with physical impairments who engaged in competitive Para sports in Saudi Arabia were interviewed. Interpretive phenomenological analysis was employed to extract themes elucidating the experiences of women athletes with physical impairments in Para sports. Results: Four dimensions were identified: (i) Exploring participation in sports; (ii) The positive impact of participation in sports; (iii) obstacles in participation in sport; and (iv) hopes and aspirations to improve participation in Para sports. Conclusion: In Saudi Arabia, participation in Para sports functions as a powerful tool for empowering and socially integrating women with physical impairments. However, these women encounter challenges in accessing sports. Achieving empowerment in Para sports necessitates the establishment of an inclusive ecosystem that celebrates diversity and equality. Collaborative efforts from governments, sports organizations, communities, and individuals are indispensable in creating an environment where women with impairments can flourish in sports.

Appraising the Physical Activity Levels of Saudis with Physical Disabilities: Effects of Disability Type, Mobility Assistive Devices, and Demographic Factors.

Physical activity (PA) has numerous health benefits for individuals with physical disabilities (IWPD). However, it is common for activity levels to fall below the suggested limits. This study aimed to evaluate the prevalence, pattern, and levels of PA among IWPD in Saudi Arabia. It also investigated the effects of individuals' type of disability, mobility assistive devices, and demographic features on PA levels. Data were collected from 238 participants, mostly male (62.2%), aged 39.76 ± 12.19 years. Among them, 19.3% had spinal conditions, 14.7% had progressive muscular dystrophy, 15.1% had multiple sclerosis, 17.6% had cerebral palsy, 16.4% had poliomyelitis, and 16.8% had limb or foot amputations. The participants were assessed using the Arabic version of the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD-AR). The results showed that 62.6% (64.9% of males and 58.9% of females) met the minimum PA guidelines specified by the WHO. The average PASIPD-AR score was 10.33 ± 10.67 MET-hours/day, indicating lower PA levels, and 8.4% of individuals did not participate in any form of PA. Significant discrepancies were detected in disability type and mobility assistive device use after age adjustment. Marital status, education, and occupation greatly affected PA components. Greater attention should be paid to promoting an active lifestyle among IWPD in Saudi Arabia.

Influence of stocking density on the growth, immune and physiological responses, and cultivation environment of white-leg shrimp (Litopenaeus vannamei) in biofloc systems.

Biofloc (BF) stands out as a promising system for sustainable shrimp farming. Optimizing various culture conditions, such as stocking density, carbohydrate source, and feeding management, is crucial for the widespread adoption of the BF system. This study compares the growth performance of white-leg shrimp (Litopenaeus vannamei) in culture ponds at low density (LD) with 50 organisms/m2 and high density (HD) with 200 organisms/m2. Post-larvae of white-leg shrimp were stocked for 16 weeks in both LD and HD groups. The LD group exhibited a superior survival rate, growth rate, and feed consumption compared to the HD group. The BF from the LD system recorded a significantly higher protein content (16.63 ± 0.21%) than the HD group (15.21 ± 0.34%). Heterotrophic bacterial counts in water did not significantly differ with stocking density. However, Vibrio count in water samples was higher in the HD group (3.59 ± 0.35 log CFU/mL) compared to the LD group (2.45 ± 0.43 log CFU/mL). The whole shrimp body analysis revealed significantly higher protein and lipid content in the LD group. In contrast, the total aerobic bacterial count in shrimp from the HD group was high, with the identification of Salmonella enterica ssp. arizonae. Additionally, Vibrio counts in shrimp samples were significantly higher in the HD group (4.63 ± 0.32 log CFU/g) compared to the LD group (3.57 ± 0.22 log CFU/g). The expression levels of immune-associated genes, including prophenoloxidase, transglutaminase, penaiedin 3, superoxide dismutase, lysozyme, serine proteinase, and the growth-related gene ras-related protein (rap-2a), were significantly enhanced in the LD group. Conversely, stress-related gene expression increased significantly in the HD group. Hepatopancreases amylase, lipase, and protease were higher in the LD group, while trypsin activity did not differ significantly. Antioxidant enzyme activity (catalase, glutathione, glutathione peroxidase, and superoxide dismutase) significantly increased in the LD group. The histological structure of hepatopancreas, musculature, and female gonads remained similar in both densities. However, negative effects were observed in the gills' histology of the HD group. These results suggest that increasing stocking density is associated with significantly negative biological, microbial, and physiological effects on white-leg shrimp under the BF system.

Knowledge and awareness of stroke in rural and urban communities.

INTRODUCTION: The average stroke morbidity rate, especially in rural communities, is higher when compared to the national average. OBJECTIVE: Identify the profile of knowledge and awareness of stroke in rural and urban communities and analyze the differences between the two. METHOD: Respondents who met the requirements answered a questionnaire containing a total of 41 items regarding knowledge and awareness of stroke. Characteristic data obtained includes age, gender, education, occupation, and ethnicity. Differences in characteristics were analyzed using Mann-Whitney, and the profiles of knowledge and awareness of stroke in rural and urban groups were analyzed using independent t tests to see differences between the two. RESULT: Differences in the characteristics of rural and urban groups were only in education (p = 0.036) and occupation (p = 0.021). The mean score of the knowledge domain for the rural group was 72.53 (SD = 11.04), for the urban group it was 81.06 (SD = 11.12). The mean score awareness of stroke domain in the rural group was 72.18 (SD = 11.01), the urban group was 85.51 (SD = 11.67). The profile of knowledge and awareness of stroke in rural communities was significantly lower than in urban communities. The significance value was (p = 0.004) for knowledge and (p = 0.002) for awareness of stroke. CONCLUSION: Based on the findings, it is reasonable to suspect that educational and occupational factors contribute to differences in the profile of knowledge and awareness of stroke in the two groups. Therefore, the stroke awareness campaign strategy for rural communities needs to be specifically designed by emphasizing/considering educational and occupational factors.

Zirconium-based hydrophobic-MOFs as innovative electrode modifiers for flibanserin determination: Exploring the electrooxidation mechanism using a comprehensive spectroelectrochemical study.

Three different types of Zr-based MOFs derived from benzene dicarboxylic acid (BDC) and naphthalene dicarboxylic acid as organic linkers (ZrBDC, 2,6-ZrNDC, and 1,4-ZrNDC) were synthesized. They were characterized using X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), Fourier-transform IR spectroscopy (FT-IR), and Transmission electron microscopy (TEM). Their hydrophilic/hydrophobic nature was investigated via contact angle measurements; ZrBDC MOF was hydrophilic and the other two (ZrNDC) MOFs were hydrophobic. The three MOFs were combined with MWCNTs as electrode modifiers for the determination of a hydrophobic analyte, flibanserin (FLB), as a proof-of-concept analyte. Under the optimized experimental conditions, a significant enhancement in the oxidation peak current of FLB was observed when utilizing 2,6-ZrNDC and 1,4-ZrNDC, being the highest when using 1,4-ZrNDC. Furthermore, a thorough investigation of the complex oxidation pathway of FLB was performed by carrying out simultaneous spectroelectrochemical measurements. Based on the obtained results, it was verified that the piperazine moiety of FLB is the primary site for electrochemical oxidation. The fabricated sensor based on 1,4-ZrNDC/MW/CPE showed an oxidation peak of FLB at 0.8 V vs Ag/AgCl. Moreover, it showed excellent linearity for the determination of FLB in the range 0.05 to 0.80 µmol L-1 with a correlation coefficient (r) = 0.9973 and limit of detection of 3.0 nmol L-1. The applicability of the developed approach was demonstrated by determination of FLB in pharmaceutical tablets and human urine samples with acceptable repeatability (% RSD values were below 1.9% and 2.1%, respectively) and reasonable recovery values (ranged between 97 and 103% for pharmaceutical tablets and between 96 and 102% for human urine samples). The outcomes of the suggested methodology can be utilized for the determination of other hydrophobic compounds of pharmaceutical or biological interest with the aim of achieving low detection limits of these compounds in various matrices.

Exploring the anti-osteoporosis potential of Petroselinum crispum (Mill.) Fuss extract employing experimentally ovariectomized rat model and network pharmacology approach.

One of the most prevalent secondary osteoporosis is ovariectomy-induced osteoporosis. Parsley (Petroselinum crispum) has potent estrogenic and antioxidant properties and was used traditionally in the treatment of amenorrhea and dysmenorrhea. The present study aimed to characterize parsley leaf extract (PLE) employing RP-HPLC-MS-MS/MS-based method and possible protective effect in ovariectomized (OVX)-induced osteoporosis in rats was assessed. Rats were randomly assigned into SHAM group, OVX group, PLE + OVX group (150 mg/kg/day, p.o), and estradiol benzoate (E2) + OVX group (30 µg/kg/day, s.c). After eight weeks following ovariectomy, biomarkers of bone strength, bone resorption, oxidative stress and histopathology were carried out. A network pharmacology approach investigated the key targets and potential mechanisms by of PLE metabolites against osteoporosis using databases: PubChem, BindingDB server, DisGeNET, ShinyGO, and KEGG Pathway. Moreover, FunRich 3.1.3, Cytoscape 3.10.0, and MOE 2019.0102 softwares were used for network pharmacology analysis and molecular docking studies. Flavones and hydroxycinnamic acid derivatives were predominant among 38 metabolites in PLE. It significantly restored bone strength and bone resorption biomarkers, osteocalcin (OST), oxidative stress biomarkers and histopathological alterations. The employed network pharmacology approach revealed that 14 primary target genes were associated with decreasing the severity of osteoporosis. Molecular docking revealed that cGMP-PKG signaling pathway has the highest fold enrichment and its downstream PDE5A. Luteolin, diosmetin, and isorhamnetin derivatives affected mostly osteoporosis targets. PLE exhibited protective action against ovariectomy-induced osteoporosis in rats and may be a promising therapy for premenopausal bone loss. cGMP-PKG signaling pathway could be a promising target for PLE in treating osteoporosis.

Sub-100 nm carriers by template polymerization for drug delivery applications.

Size-controlled drug delivery systems (DDSs) have gained significant attention in the field of pharmaceutical sciences due to their potential to enhance drug efficacy, minimize side effects, and improve patient compliance. This review provides a concise overview of the preparation method, advancements, and applications of size-controlled drug delivery systems focusing on the sub-100 nm size DDSs. The importance of tailoring the size for achieving therapeutic goals is briefly mentioned. We highlight the concept of "template polymerization", a well-established method in covalent polymerization that offers precise control over molecular weight. We demonstrate the utility of this approach in crafting a monolayer of a polymer around biomolecule templates such as DNA, RNA, and protein, achieving the generation of DDSs with sizes ranging from several tens of nanometers. A few representative examples of small-size DDSs that share a conceptual similarity to "template polymerization" are also discussed. This review concludes by briefly discussing the drug release behaviors and the future prospects of "template polymerization" for the development of innovative size-controlled drug delivery systems, which promise to optimize drug delivery precision, efficacy, and safety.

Geochemistry of Liquid Hydrocarbons and Natural Gases Combined with 1D Basin Modeling of the Oligocene Shale Source Rock System in the Offshore Nile Delta, Egypt.

The current study aims to integrate the geochemical characteristics of the Oligocene shale source rock system, oil, condensate, and natural gas samples in the Oligocene sandstone reservoirs from three exploration wells located in the offshore Nile Delta, East Mediterranean Sea, using organic geochemistry and a 1D basin modeling scheme. The Tineh shales exhibit total organic carbon values ranging between 0.90 and 1.89 wt %, along with hydrogen index values in the range of 54-240 mg hydrocarbon/g rock. The geochemical characterization suggests that the shale intervals of the Oligocene Tineh Formation contain type II-III and type III kerogens and, thereby, could be regarded as promising oil- and gas-prone source rocks with high contributions of gas generation potential. The study also reconstructs the 1D thermal and burial history models, showing that the Oligocene Tineh source rock system is in the main oil and wet gas generation phases from the late Miocene to the present time. The simulated basin models reveal the transformation (TR) of 10-50% kerogen to oil during the late Miocene-early Pliocene period and that the Oligocene Tineh source rock system has larger oil generation and expulsion competency, with a TR value of up to 65% during the early Pliocene-Pleistocene time period. The thermogenic gas was also formed during this time and continued to the present day. This study also investigated the presence of oil and condensate in the Oligocene sandstone reservoir samples and revealed that they were generated from mature source rock, ranging from moderately to highly mature stages. This source rock unit was deposited in fluvial to fluvial-deltaic environments under oxic mixed organic conditions and accumulated during the Tertiary time, as evidenced by the presence of the oleanane biomarker dating indicator. The molecular and isotope compositions of natural gases revealed that most of the natural gases in the Oligocene sandstone reservoir are mainly thermogenic methane gases that were generated from mainly mixed organic matter. The thermogenic methane gases were formed mainly from secondary cracking of oil and gas, with small contributions of primary kerogen cracking. The properties of natural gases together with oil and condensate in the Oligocene reservoir rocks suggest that most of the thermogenic methane gases and associated liquid hydrocarbons are derived primarily from the Oligocene shale source rock system and formed by primary kerogen cracking and secondary oil and oil/gas cracking in different thermal maturity stages. Therefore, the Oligocene Tineh Formation can be regarded as self-source generation and self-reservoir rock; hence, an intensive oil exploration and production program can be recommended whenever the Tineh source rock system is is well developed and deeply buried.

Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa.

Background: An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. Methods: Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. Results: The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four bla OXA-48 isolates were susceptible to carbapenems. Bla NDM-1 (n = 13) and bla OXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. Conclusions: The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.

Synthesis, antimicrobial, and in silico studies of c5'-O-substituted cytidine derivatives: cinnamoylation leads to improvement of antimicrobial activity.

Nucleoside derivatives are important therapeutic drugs that have drawn significant attention recently. In this study, cytidine (1) was first exposed to react with cinnamoyl chloride in N,N-dimethylformamide, and trimethylamine to obtain 5'-O-(cinnamoyl)cytidine, which was further treated with several acylating agents to obtain a series of 2',3'-di-O-acyl derivatives. The chemical structures of the synthesized compounds were established through spectral, analytical, and physicochemical techniques. In vitro antimicrobial efficacy was evaluated, and the antimicrobial effect was greater than that of the precursor compound; in particular, compound 3 exhibited the most promising activity. Cytotoxicity measurements revealed that the compounds demonstrated a decreased degree of toxicity. A structure-activity relationship (SAR) study showed that the ribose moiety combined with the acyl chains (C-12/C13) and (C6H5CH = CHCO) had enhanced effects on bacteria and fungi. Molecular docking was applied for the potential inhibitors (3, 4, and 6) to predict their mode of action and confirm their efficacy against isozymes, tubulin-like protein TubZ, Bacillus cereus [PDB: 4ei9], and dihydrofolate reductase of Aspergillus flavus [PDB: 6dtc]. A molecular dynamics simulation study was performed to evaluate the deformability, flexibility, and stiffness of the target enzyme residues. Density functional theory (DFT) indicates the high polarizability and chemical reactivity of the synthesized compounds. The ADMET (absorption, distribution, mechanism, excretion, and toxicity) study suggested that all the designed molecules have moderate human intestinal absorption and good distribution values in addition to the absence of CNS side effects and structural toxicity. Above all else, these cytidine derivatives possess potential antimicrobial behavior, thereby rendering them suitable drug candidate(s) for additional exploration.

A series of cinnamoyl cytidine derivatives were designed and synthesized. The chemical structures of these newly acylated derivatives were confirmed by state-of-the-art spectroscopic techniques.The antimicrobial activity of the synthesized cytidine derivatives was greatly enhanced by the addition of several aliphatic and aromatic acyl groups to the cytidine structure.The cytotoxicity assessment indicated that the compounds exhibited less toxicity.In a molecular docking investigation of the Bacillus cereus tubulin-like protein TubZ and Aspergillus flavus dihydrofolate reductase inhibitors, the catalytic active site revealed promising binding and interaction scores.A molecular dynamics simulation study was performed to evaluate the deformability, flexibility, and stiffness of the target enzyme residues toward the bacterio-fungal dual active inhibitor 4.In silico ADMET studies showed that all the provided compounds had moderate human intestine absorption, good distribution, no CNS side effects, and structural toxicity toward PAINS.

Engineered Microenvironmental Cues from Fiber-Reinforced Hydrogel Composites Drive Tenogenesis and Aligned Collagen Deposition.

Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber-reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber-reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor ß3 drives a cell fate switch toward pro-regenerative or pro-fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber-reinforced hydrogels critically mediates the alignment of de novo collagen fibrils, reflecting native tendon architecture. These findings inform the design of cell-free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load-bearing connective tissues.

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies.

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection's spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds' physical and chemical features, including molecular dynamic (MD) simulations, protein-ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

The ethnopharmacological study of plant drugs used traditionally in Djibouti for malaria treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Djibouti was a country where malaria has been endemic for centuries. The local population use the plants as repellents or first aid for uncomplicated malaria. AIM OF THE STUDY: The aim was, for the first time, to collect and identify plants used by the local population to treat malaria and select the most interesting plants (those that are more commontly used, more available, and have fewer studies). These plants were evaluated for their antiplasmodial activity as well as their cytotoxicity on human cell lines for the most active ones. MATERIALS AND METHODS: A semi-structured questionnaire was developed for this study to collect information about the use and identity of botanical drugs used to treat malaria. The use-reports (percentage) of each plant were recorded to determine their use importance. Also, the availability status of the plants was assessed; and those in critical condition were discarded excluded from further study. Fifteen plants, out of the 41 listed, were extracted with hydro alcohol, ethyl acetate, and dichloromethane for biological testing. Chloroquine-resistant strain FcB-1 of P. falciparum and a human diploid embryonic lung cell line were used for the antiplasmodial test, and to assess the cytotoxicity for human cells respectively. Preliminary analysis of extract constituents was carried out using thin layer chromatography (TLC). RESULTS: This study identifies 41 plant taxa belonging to 32 families and records their use against malaria. Balanites rodunfolia, belonging to the Zygophyllaceae family, was the most commonly used plant, representing 44 % of use-reports. It was followed by Cadaba rodunfolia (15 %) from the Capparaceae family, and then the three species of Aloe: Aloe djiboutiensis (8.2 %), Aloe ericahenriettae (3.4 %), and Aloe rigens (3.4 %) from the Asphodelaceae family. The leaves are the most commonly used part of the plants to treat malaria, accounting for 76 % of usage. The preparation methods were decoction (52 %), maceration (29 %), and boiling (19 %). The administration routes were by oral (80 %), inhalation 19 %), and bathing (1 %). The best antiplasmodial activities were observed in the dichloromethane extracts of Cymbopogon commutatus and the ethyl acetate extracts of Aloe rigens and Terminalia brownii, with IC50 values of 9.8, 5, and 7.5 µg/mL, respectively. Their toxicity/activity levels were very favorable with selectivity indices of 5.6, 8.1, and 11.8 for C. commutatus, A. rigens, and T. Brownii, respectively. CONCLUSION: Forty-one species of botanical drugs were listed as being used to treat malaria in Djibouti. All fifteen selected species showed antiplasmodial activity (IC50 < 50 µg/mL). This work will help guide the valorization of botanical drugs used to treat malaria in Djibouti.

Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. PATIENTS AND METHODS: Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. RESULTS: Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. CONCLUSIONS: Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.

Cross-Cultural Adaptation and Validation of the Arabic Version of the Physical Activity Scale for Individuals with Physical Disabilities in Saudi Arabia (PASIPD-AR).

This study aimed to cross-culturally adapt and validate the Arabic version of the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) with Saudi Arabian participants. The study encompassed four distinct stages: (i) translation and subsequent back-translation; (ii) a preliminary assessment aimed at evaluating the quality of the translated scale; (iii) an assessment of the reliability of the measures employed; and (iv) a comprehensive examination of the validity of the measures. A sample of Saudi Arabian participants with physical disabilities (N = 206) took part, ranging in age from 18 to 70 years old, with an average age of 39.56 years and a standard deviation of 12.16. The findings obtained from the reliability tests indicated a notable level of internal consistency and stability. Experts and confirmatory factor analysis were employed to establish the face, content, and construct validity. The findings of the assessment of the Arabic version of PASIPD demonstrated a satisfactory degree of reliability and validity, rendering it suitable for implementation within the Saudi Arabian setting.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.