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Naeem Mubarak,1 Sarwat Ali Raja,1 Asma Sarwar Khan,1,2 Sabba Kanwal,1 Nasira Saif-ur-Rehman,1 Muhammad Majid Aziz,1 Irshad Hussain,3 Ernieda Hatah,4 Che Suraya Zin5 1Department of Pharmacy Practice, Lahore Medical & Dental College, University of Health Sciences, Lahore, Punjab, Pakistan; 2Department of Pharmacy Practice, University of Health Sciences, Lahore, Punjab, Pakistan; 3Department of Pharmacy, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Sindh, Pakistan; 4Department of Pharmacy, The National University of Malaysia, Bangi, Malaysia; 5Kulliyyah of Pharmacy, International Islamic University, Kuantan, MalaysiaCorrespondence: Naeem MubarakLahore Medical & Dental College, University of Health Sciences, Tulspura, North Canal Bank, Lahore, 53400, PakistanTel +92 42-37392208Email naeem.mubarak@lmdc.edu.pkChe Suraya ZinUniversiti Islam Antarabangsa, Malaysia Kampus Kuantan, Pahang Darul Makmur, Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, Kuantan, Pahang, 25200, MalaysiaTel +60 11-14881605Email chesuraya@iium.edu.myBackground: There is a growing global interest in formulating such policies and strategic plans that help devise collaborative working models for community pharmacists (CPs) and general practitioners (GPs) in primary care settings.Objective: To conceptualize a stakeholder-driven framework to improve collaboration between CPs and GPs in Malaysian primary care to effectively manage medicines in chronic diseases.Design and Setting: A qualitative study that involved individual semi-structured interviews of the leadership of various associations, guilds, and societies representing CPs, GPs, and Nurses in Malaysia.Methods: This study collected and reported data in accordance with the guidelines of the Consolidated Criteria for Reporting of Qualitative Studies. Key informants were recruited based on purposive (expert) sampling. Interviews were transcribed verbatim and data were coded based on the principles of thematic analysis in NVivo.Results: A total of 12 interviews (5 CPs, 5 GPs, and 2 nurses) were conducted. Five themes emerged: Theme 1 highlighted a comparison of community pharmacy practice in Malaysia and developed countries; Theme 2 involved current practices in Malaysian primary care; Theme 3 encompassed the advantages of CP–GP collaboration in chronic diseases; Theme 4 highlighted the barriers which impede collaboration in Malaysian primary care; and Theme 5 delineated the way forward for CP–GP collaboration in Malaysia.Conclusion: The actionable insights obtained from the Malaysian stakeholders offered an outline of a framework to enhance collaboration between CPs and GPs in primary care. Generally, stakeholders were interested in CP–GP collaboration in primary care and identified many positive roles performed by CPs, including prescription review, adherence support, and patient education. The framework of the way forward includes: separation of CP and GP roles through a holistic revision of relevant legislation to grant an active role to CPs in chronic care; definition of protocols for collaborative practices; incentivization of both stakeholders (CPs and GPs); and design and implementation of an effective regulatory mechanism whereby the Malaysian Ministry of Health may take a leading role.Keywords: community pharmacist, general practitioner, chronic disease, collaborative care, Malaysia, qualitative research medicine management

The mechanical properties of γ-irradiated ethylene propylene diene monomer (EPDM)/high styrene-butadiene rubber (HSBR) blends were investigated with special reference to the effects of blend ratio. Among the blends, the one with 80/20 EPDM/HSBR has been found to exhibit the highest tensile, hardness, thermal, and abrasion properties. The effect of γ-irradiation dose on the mechanical properties namely tensile strength and elongation at break was investigated. The effect of silane coupling agent on the mentioned properties of the EPDM/HSBR blend was studied. The results showed that the mechanical and the thermal properties of the γ-irradiated EPDM/HSBR blend improved with the addition of the silane coupling agent due to the increase in the cross-linking density. The inclusion of both the 30 phr fumed silica and N, N - m -phenylenedimaleimide coagent in the 80/20 EPDM/HSBR nanocomposite irradiated to 150 kGy leads to a synergistic effect. Thermogravimetric analysis was carried out to analyze the thermal stability of the nanocomposites. The mechanical properties have been interpreted in terms of the morphology of the blends as attested by scanning electron microscope. [ABSTRACT FROM AUTHOR]

Objective. CD5+ B cells comprise a unique subset of B cells that modulates innate as well as autoimmune systems. The aim of this study was to investigate alterations of the circulating CD5+ B-cell subset in patients with inflammatory bowel disease (IBD) by evaluating various clinical parameters, including therapeutic regimens. Material and methods. Thirty-four patients with ulcerative colitis (UC), 19 patients with Crohn's disease (CD), and 46 healthy control subjects were enrolled in this study. CD5+ B cells in peripheral blood collected from each subject were analyzed by flow cytometry. Multiple regression analysis was carried out to evaluate the factors related to the circulating CD5+ B-cell subset in the IBD patients. In an in vitro examination, dexamethasone-induced apoptosis in peripheral blood B cells was examined by detecting cell surface binding of the annexin-V antibody. Results. Age and gender in the control subjects did not influence the circulating CD5+ B-cell subset. Multiple regression analysis showed that the presence of UC, corticosteroid therapy, and number of white blood cells in peripheral blood each had a significant influence in decreasing the number of circulating CD5+ B cells in the IBD patients. Furthermore, in vitro results showed that dexamethasone treatment significantly induced apoptosis in CD5+ B cells, though apoptosis was similarly observed in CD5- B cells. Conclusions. CD5+ B cells may be involved in the pathogenesis of UC, and modulation of this subset by corticosteroid therapy may play a role in the treatment of IBD patients. [ABSTRACT FROM AUTHOR]

Background : Due to technological advancements, the demand for easily accessible and convenient healthcare services is rising globally. Thus, telehealth is gaining momentum that was previously unheard of. The Kingdom of Saudi Arabia (KSA) actively embraces digital innovation in the healthcare industry through its ambitious Vision 2030 initiative. This study aimed to assess the perceived usability of telehealth for personalized healthcare among the KSA adult population in the post-COVID-19 era. Methods : This cross-sectional study used a convenience sample of 975 adults from the general population in KSA. A digital survey was used for data collection through Survey Monkey software. It contained two sections: personal and health data and the Telehealth Usability Questionnaire (TUQ). The data was collected over three months (July-September 2024) and investigated using the multinomial logistic regression analysis. Results : This study showed that 59.8% of the participants have initiated telehealth service use before the COVID-19 pandemic, and the most frequently used services are the issuance of sick leave (30.6%), tele-prescription (29.0%), virtual consultation (20.0%), tele-mental health services (19.4%), telemonitoring (18.6), and tele-referral (18.2%). A high total telehealth usability score was observed among 60.4% of the participants: 72.7% perceive telehealth as highly useful, 76.4% perceive it as easy to use, 60.1% have high satisfaction and intention for future use, 57.4% perceive high interface quality, and 51.8% perceive a high interaction quality. Conversely, 45.8% perceive low reliability of the telehealth system. Multinomial logistic regression showed that low education (AOR = 2.04; 95% CI = 1.16-4.85) and using virtual consultation (AOR = 0.98; 95% CI = 0.38-0.99) were predictors of low telehealth usability. However, being female (AOR = 1.67; 95% CI = 1.27-2.55), being in higher education (AOR = 1.47; 95% CI = 1.02-2.34), and living in the central KSA region (AOR = 1.37; 95% CI = 1.10-2.23) were predictors of high telehealth usability. Working status, income, and presence of chronic disease were not statistically significant predictors. Conclusions : Telehealth services have been highly usable in KSA even before the COVID-19 pandemic, with commonly used asynchronous services. Many social, technological, and system-related factors could affect the user experience and system reliability. Hence, telehealth developments are recommended to overcome such barriers, with future initiatives focusing on the flexibility and convenience of telehealth systems.

Purpose: Pediatric hydrocephalus imposes a significant clinical and financial burden in developing countries. Traditional treatment by ventricular shunting in this setting suffers a high rate of shunt infection and malfunction. This study aims at assessing the efficacy and safety of endoscopic third ventriculostomy (ETV), either alone or combined with choroid plexus cauterization (CPC), for preventing shunt dependence in pediatric hydrocephalus within a healthcare setting of a tertiary hospital in Egypt., Methods: A prospective clinical case series included patients aged 16 years or younger with clinical manifestations of hydrocephalus requiring CSF diversion. Cases with active infection or brain imaging showing prohibitive anatomical distortion or multiloculated hydrocephalus were excluded. Failed ETV + / - CPC cases were categorized into early (< 3 months) and late (> 3 months) failure groups, each with specific management strategies., Results: A total of 40 patients were admitted to Ain Shams University Hospital between March 2022 and August 2023 and underwent ETV/CPC (n = 32) for those younger than 2 years and ETV alone (n = 8) for patients > 2 years old, using a flexible neuroendoscope. Aqueductal stenosis was the most common etiology, observed in 13 patients (32.5%), followed by Chiari type 2 in 11 patients (27.5%), and post-infectious causes in 6 patients (15%). The median age of the patients was 5.05 months (mean 22 months; range 0.23-169.27 months). The median preoperative ETV success score (ETVSS) was 50. Overall, 25 patients (62.5%) achieved successful outcomes following either ETV alone or ETV/CPC procedures, with no procedure-related morbidity or mortality. Fifteen patients (37.5%) experienced ETV failure, of whom 6 underwent ETV redo procedures. Across the entire cohort, 28 patients (70%) remained shunt-free, with a mean follow-up of 12 months., Conclusion: The addition of CPC to ETV (for patients < 2 years) using the flexible scope demonstrates effectiveness in decreasing the necessity for shunt placement in younger patients with a likelihood of ETV failure. Moreover, being a safe procedure, it supports a sustainable and cost-effective approach to hydrocephalus treatment., Competing Interests: Declarations. Ethical approval: This study was approved by the Research Ethics Committee (REC) at the Faculty of Medicine, Ain Shams University, under the number code FWA 000017585, FAMSU M D 43/2021. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Improving death certification of Under 5 Mortality (U5M) is an important pre-requisite for improving child health. This study aimed to obtain a clear and comprehensive understanding of the process of death registration of U5M and address the challenges of accurate certification faced by physicians at hospitals and health offices., Methods: A qualitative descriptive study was performed by conducting 10 Focus Group Discussions (FGDs) with physicians who are actively involved in the certification of U5M. Physicians were invited to participate from primary health care units, health offices, district and general hospitals in Cairo, Giza and Assiut Governorates. Field visits of health offices were performed to observe the procedure of death registration, visualize a sample of the hospitals' Death Notification Forms (DNFs) and death certificates of U5M, and explore the used electronic system of death registration. Data analysis was performed using inductive thematic analysis., Results: The study clarified the procedure of death certification of U5M, starting from hospitals and ending at health offices. It was evident that there is a considerable deficiency in the system of registration and coding causes of death. Physicians of hospitals had a negative attitude regarding death registration. They were found to have deficient knowledge about standards of death certification. They had difficulty defining and reporting the chain of events leading to death. Poor diagnostic facilities hindered physicians from accurately reporting COD. Fear of legal accountability was a cause of avoiding detailed COD. For physicians in the health offices, other challenges were mentioned such as assigning junior physicians to manage the task of writing DNFs, poor quality of hospital reports and the unrealistic ICD-10 codes., Conclusion: Improving the accuracy of writing DNFs in hospitals is essential for providing reliable U5M statistics. Practical training of physicians, especially the junior ones, on ICD-10 classification and on identification and writing direct and indirect COD in the allocated lines in the death certificates is a priority. Establishing an audit system to assess the quality of the process of certification and updating the software of the electronic system for data entry would have a great impact., Competing Interests: Declarations. Ethics approval and consent to participate: Administrative approval was obtained from the MOHP PHC, Preventive and Curative sectors and ethical approval was obtained from the Research ethics committee of Assiut University and the IRB of MOHP. Participants were explained the objectives of the study, how confidentiality is protected; through replacement of names by letters in the transcripts and keeping the digital recordings only with the researchers. No bystanders from the MOHP administrative level were allowed to attend the meetings. All participants were assured that their participation in the study is completely voluntary. Written informed consent was obtained from all participants of the study. No data allowing the identification of the study participants was presented in the data analysis. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This prospective study aimed to compare ultra-high molecular weight polyethylene (UHMWPE) with polyetheretherketone (PEEK) in computer-designed patient-specific implants (PSIs) for cranial defect reconstruction, in terms of complications and aesthetic outcomes. Primary or secondary cranioplasty-eligible patients were included, while patients with active infection or hydrocephalus, or unfit for general anesthesia, were excluded from the study. All the implants were designed and fabricated by the same maxillofacial surgeon using CAD/CAM technology. UHMWPE PSIs were used in group 1 and PEEK PSIs in group 2. Technically, UHMWPE could be milled to a thinner margin thickness than PEEK, which resulted in better handling properties and a smoother end finish. All patients were evaluated over a period of 6 months in terms of overall complications or implant failure as the primary outcome, according to Clavien-Dindo (CVD) grading, and cosmetic satisfaction with the aesthetic results, using a Likert scale, as the secondary outcome. In total, 22 cranioplasty patients were included, with a mean age of 30.8 years (SD = 16.3). Across both groups, 17 patients (77.3%) did not develop postoperative complications. These occurred in three patients in group 1 (CVD grade I, II, and IIIb) (27.3%) and in two patients in group 2 (CVD grade II, IIIa, and IIIb) (18.2%), with no statistical difference (p = 0.6). None of the cases in both groups developed any clinical or radiographic signs of infection, or suffered implant failure. The mean satisfaction score was 4.8 in group 1 and 4.5 in group 2 (SD = 0.6). The difference in satisfaction scores between the two was not statistically significant (p = 0.23). Although UHMWPEE was comparable to PEEK in terms of overall complication rates and cosmesis after craniectomy, UHMWPEE as a material exhibited greater resiliency in technically challenging cases with large, complex/midline-crossing designs, previously fitted meshes, or single-stage resection-reconstruction, allowing better marginal adaptation., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl 3 ) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl 3 /D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl 3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl 3 /D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management., 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 © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

This study aims to evaluate the effect and underlying mechanism of ferulic acid (FA) in alleviating the acute liver injury by ionizing radiation (IR) in vivo. Rats were divided into 4groups (Groups: control, 6Gy irradiated (IRR), FA (50 mg/kg) and FA + IRR). The results showed that FA can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, FA prevented IR-induced liver fibrosis and blocked the JAK/STAT signaling pathway to effectively inhibit the hepatic inflammatory response; and inhibited IR-induced oxidative stress (OS) by upregulating the Nrf2 signaling pathway and promoting the synthesis of several antioxidants. Moreover, FA inhibited ferroptosis in the liver by stimulating the expression of GPX4 and SLC7A11. FA reduced lipid peroxidation by downregulation of the reactive oxygen species (ROS) production and iron aggregation, thus inhibiting ferroptosis and alleviating IR-induced liver injury. In conclusion, the current study suggests the potential complex mechanisms underlying the mitigating impact of FA in IR-induced ferroptotic liver damage., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In an effort to support the global fight against tuberculosis (TB), which is widely recognized as the most lethal infectious disease worldwide, we present the design and synthesis of new benzo[b]thiophene-based hybrids as promising candidates for the management of multidrug-resistant (MDR)/extensively drug-resistant (XDR) Mycobacterium tuberculosis. The isatin motif was incorporated into the target hybrids as it represents a privileged scaffold in antitubercular drug discovery. Since lipophilicity plays a pivotal role in the anti-TB agents' activity, the lipophilicity of the target hybrids was manipulated via the development of two series of N-1 methyl and N-1 benzyl substituted isatins (6a-h and 9a-h, respectively). Screening of the target hybrids was first performed against drug-sensitive M. tuberculosis (ATCC 25177). The structure-activity relationship outputs highlighted that incorporation of 3-unsubstituted benzo[b]thiophene and 5-methoxy isatin moieties was favorable for the antimycobacterial activity. Thereafter, the most potent molecules (6b-h, 9c-e, and 9h) were evaluated against the resistant strains MDR-TB (ATCC 35822) as well as against XDR-TB (RCMB 2674) where they displayed promising activity. To evaluate the safety of the target hybrids, an sulforhodamine B assay was conducted to determine their possible cytotoxic effects on VERO cells., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177. Potent compounds 6b, 6d, 6f, 6h, 7a, 7b, 7d, 7f, 7h and 7i were furtherly assessed versus resistant MDR-TB and XDR-TB. Structure activity relationship investigation of the synthesized compounds was illustrated, accordingly. Superlative potency was unveiled for compound 6h (MIC = 0.48, 1.95 and 7.81 µg/mL for ATCC 25177 sensitive TB strain, resistant MDR-TB and XDR-TB, respectively). Moreover, validated in vivo pharmacokinetic study was performed for the most potent derivative 6h revealing superior pharmacokinetic profile over the reference drug. For further exploration of the anti-tubercular mechanism of action, molecular docking was carried out for the former compound in DprE1 active site as one of the important biological targets of TB. The binding mode and the docking score uncovered exceptional binding when compared to the co-crystallized ligand suggesting that it maybe the underlying target for its outstanding anti-tubercular potency., 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 © 2023 Elsevier Inc. All rights reserved.)

Introduction: Citrus sinensis L. is a candidate plant with promising antimicrobial potential. In the current study, the phytochemical investigation of C. sinensis leaf extract led to the isolation of three coumarins, namely bergapten, xanthotoxin, and citropten., Methods: The chemical structures of the isolated coumarins were elucidated using NMR and ESI-MS techniques. The total aqueous ethanol leaf extract and the isolated coumarins were evaluated for their antimicrobial effects against Helicobacter pylori using the MTT-micro-well dilution method and its anti-biofilm activity using MBEC assay, as compared to clarithromycin., Results: The results showed that citropten scored the lowest MIC value at 3.9 μg/mL and completely inhibited the planktonic growth of H. pylori . In addition, it completely suppressed H. pylori biofilm at 31.25 μg/mL. These findings have been supported by molecular docking studies on the active sites of the H. pylori inosine 5'-monophosphate dehydrogenase ( Hp IMPDH) model and the urease enzyme, showing a strong binding affinity of citropten to Hp IMPDH with seven hydrogen bonds and a binding energy of -6.9 kcal/mol. Xanthotoxin and bergapten showed good docking scores, both at -6.5 kcal/mol for Hp IMPDH, with each having four hydrogen bondings. Furthermore, xanthotoxin showed many hydrophobic interactions, while bergapten formed one Pi-anion interaction. Concerning docking in the urease enzyme, the compounds showed mild to moderate binding affinities as compared to the ligand. Thus, based on docking results and good binding scores observed with the Hp IMPDH active site, an in-vitro Hp IMPDH inhibition assay was done for the compounds. Citropten showed the most promising inhibitory activity with an IC 50 value of 2.4 μM. Conclusion : The present study demonstrates that C. sinensis L. leaves are a good source for supplying coumarins that can act as naturally effective anti- H. pylori agents., 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction  Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures. Objective  In this randomized study, we evaluated the use of throat packs soaked with K-Y jelly for POST outcomes in patients submitted to nasal surgery. Methods  The present double-blinded, randomized, controlled study included 140 ASA I-II patients undergoing nasal surgery under general anesthesia. Patients received either or K-Y jelly or water-soaked X-ray detectable throat packs fully inserted into the mouth to occlude the oropharynx. Results  Comparison between the studied groups regarding the severity of POST assessed by visual analog scale revealed significantly lower POST levels in the K-Y jelly group on recovery from anesthesia, and at 2, 4, and 6 hours postoperatively. Conclusions  The use of K-Y jelly-soaked throat packs was associated with less severe POST after nasal surgery., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Objectives: Exposure of spleen tissues to ionizing radiation during radiotherapy can induce cellular stress and immune-dysfunction leading to cellular senescence., Introduction: The process of a cancerous development is facilitated by the accumulation of senescent cells. This justifies the incorporation of anti-senescent medications during splenic irradiation (SI)., Methods: In this study senescence was induced in the spleen of male albino rats by radiation exposure (5Gy-single whole body gamma-irradiation) then after 2 weeks, oral astaxanthin regimen was started once daily in a dose of 25 mg/kg for 7 consecutive days. Concurrent control groups were carried out., Results: the present data reflected that irradiation provoked an increase in the oxidative stress biomarkers (nitric oxide, lipid peroxidation and total reactive oxygen species levels)and the inflammatory biomarkers (Myeloperoxidase and interleukin-6). In addition irradiation led to the over expression of stimulator of interferon genes (cGAS-STING), mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) along with the lactate dehydrogenase (LDH), cyclin-dependent kinase inhibitor 1 (p21) cyclin-dependent kinase inhibitor 2A (p16) increment with elevation of tumor suppressor protein (p53) level. However, reduced glutathione contents and catalase activity were reduced post irradiation in spleen tissues, all these changes reflecting induction of cellular senescence. Astaxanthin treatment showed an improvement in the antioxidant/oxidative stress balance, inflammatory biomarkers, histopathological examination and immunohistochemical expressions of the tested proteins in the irradiated rats., Conclusion: the current findings offer a new insight into the senomorphic effect of astaxanthin following radiation-induced spleen senescence via STING, mTOR, and TLR4 signalling pathways., 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.

Objectives: Transcerebellar diameter (TCD) has been utilized prenatally as a tool to estimate gestational age (GA) when fetal growth aberrations are suspected. Traditionally, first trimester ultrasound (1TUS) has been the gold standard of dating a pregnancy in spontaneous pregnancies. We sought to determine if neonatal TCD measurement was as accurate as 1TUS in the estimation of postconceptual gestational age (PCGA)., Methods: A retrospective cohort from a registry of high-quality transmastoid views of consecutive patients from July 2019 to November 2020, delivered from 24 to 34 weeks GA, and with a 1TUS were included. The reference PCGA was the sum of the GA at delivery by 1TUS and day of life. The PCGA by TCD was calculated from Chang et al for GA by TCD. Reference and experimental values were compared by correlation, agreement within 7 days, and Bland-Altman analysis., Results: Of the 154 individual patients in the registry of high-quality transmastoid views during the study period, 62 met inclusion and exclusion criteria. PCGA by 1TUS and TCD were highly correlated (r = 0.86, P < .001; κ = 47% agreement within 7 days of PCGA). The bias of PCGA by TCD was 4.6 days earlier than the PCGA by 1TUS (95% confidence interval of agreement: -29.2, 20)., Conclusions: PCGA estimation by neonatal transmastoid TCD was highly correlated with that of 1TUS. It generally underestimates GA by 4.6 days. This relationship warrants further investigation to determine if this method of estimating PCGA in undated gestations is generalizable., (© 2023 American Institute of Ultrasound in Medicine.)

For chemical modification, p-aminobenzoic acid was incorporated into chitosan Schiff base (ACsSB) and chitosan (ACs). Two ACs-based CuO nanoparticles composites; ACs/CuONPs-1 % and ACs/CuONPs-5 %, were also synthesized. Their structures were emphasized utilizing several analytical techniques; elemental analysis, FTIR, 1 H NMR, XRD, SEM, EDX and TEM. Compared with standard cyclooxygenase (COX) inhibitor, Celecoxib, the prepared biomaterials showed in vitro selective inhibitory effectiveness against COX-2 enzyme that could be sorted, according to their MIC values that produce 50 % inhibition of COX-2 enzyme activity, as follows: Celecoxib (0.28 μg/mL) > ACs/CuONPs-5 % (4.1 μg/mL) > ACs/CuONPs-1 % (14.8 μg/mL) > ACs (38.5 μg/mL) > ACsSB (58.9 μg/mL) > chitosan (>125 μg/mL). Further, ACs/CuONPs-5 % has more in vitro inhibition efficiency towards Helicobacter pylori (H. pylori) than the other prepared biomaterials. Interestingly, the MIC value of 100 % growth inhibition of H. pylori for ACs/CuONP-5 % is equal to that of drug Clarithromycin (1.95 μg/mL). Thus, ACs/CuONPs-5 % has a promising potential as anti-H. pylori and selective anti-inflammatory agent. ACs/CuONPs-5 % is safe on the human gastric normal cells (GES-1). Therefore, amalgamation of both p-aminobenzoic acid and CuONPs into chitosan extremely promoted its anti-inflammatory and anti-H. pylori activity. This is a promising approach to achieve methods successful to compete the conventional antibiotics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cancer is a leading cause of death globally and has been associated with Mycobacterium tuberculosis (Mtb). The angiogenesis-related VEGFR-2 is a common target between cancer and Mtb. Here, we aimed to synthesize and validate potent dual human VEGFR-2 inhibitors as anticancer and anti-mycobacterial agents. Two series of 1,2,4-triazole-based compounds (6a-l and 11a-e) were designed and synthesized through a molecular hybridization approach. Activities of all synthesized compounds were evaluated against human VEGFR-2 in addition to drug-sensitive, multidrug-resistant and extensive-drug resistant Mtb. Compounds 6a, 6c, 6e, 6f, 6h, 6l, 11a, 11d and 11e showed promising inhibitory effect on VEGFR-2 (IC 50  = 0.15 - 0.39 µM), anti-proliferative activities against cancerous cells and low cytotoxicity against normal cells. The most potent compounds (6e and 11a) increased apoptosis percentage. Additionally, compounds 6h, 6i, 6l and 11c showed the highest activities against all Mtb strains, and thus were evaluated against enoyl-acyl carrier protein reductase (InhA) which is essential for Mtb cell wall synthesis. Interestingly, the compounds showed excellent InhA inhibition activities with IC 50 range of 1.3 - 4.7 µM. Docking study revealed high binding affinities toward targeted enzymes; human VEGFR-2 and Mtb InhA. In conclusion, 1,2,4-triazole analogues are suggested as potent anticancer and antimycobacterial agents via inhibition of human VEGFR-2 and Mtb InhA., 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 © 2023 Elsevier Inc. All rights reserved.)

Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been informed to be beneficial in the treatment of stress-related oxidative impairment. In the present study, we examined the protective role of crocin against testicular damage induced by radiation (acute and fractionated) and the alteration of the AKT/FOXO signaling pathway. Male Wister albino rats were exposed to acute dose of 6 Gy and a fractionated dose of gamma radiation (2 Gy every 2 days up to 6 Gy total doses). Rats were pretreated intraperitoneally with crocin in a dose of 50 mg/kg for seven consecutive days prior to exposure to irradiation at a level of 6 Gy and during the fractionated irradiation of rats. Control groups were run concurrently. Ionizing radiation caused changes in the level of oxidative stress biomarkers manifested as elevation of thiobarbituric acid reactive substance, total nitrate/nitrite and reactive oxygen species (ROS) associated with a decrease in catalase as well as in the level of inflammatory parameters (decrease in expression of Nrf2 which was related to a significant increase in expression of NF-κB p65). Irradiation produced cellular damage characterized by an increase in serum lactate dehydrogenase. These findings were aligned with increased expression of the forkhead box O-1 (FOXO-1) and activation of protein kinase B (AKT) pathway. Irradiation of rats led to reduction in serum testosterone level and testicular weights. Pretreatment with the indicated dose of crocin shielded against the changes in all the evaluated parameters. Administration of crocin can be introduced as a novel preclinical approach for regulation of testicular damage induced by radiation; via controlling the ongoing oxidative stress and inflammatory reaction as well as activation FOXO/AKT signaling pathway., (© 2023 Wiley Periodicals LLC.)

Context: Date palm waste is an agricultural waste that accumulates in massive amounts causing serious pollution and environmental problems., Objectives: Date palm trees, Phoenix dactylifera Linn CV 'Zaghloul' (Arecaceae) grown in Egypt, leave behind waste products that were investigated to produce compounds with anti- Helicobacter pylori and anti-inflammatory activities., Materials and Methods: Chromatographic workup of P. dactylifera aqueous methanol extract derived from fibrous mesh and fruit bunch (without fruit) afforded a new sesquiterpene lactone derivative, phodactolide A ( 1 ), along with ten known compounds ( 2-11 ), primarily identified as polyphenols. Chemical structures were unambiguously elucidated based on mass and 1D/2D NMR spectroscopy. All isolated compounds were assessed for their activities against H. pylori using broth micro-well dilution method and clarithromycin as a positive control. The anti-inflammatory response of isolated compounds was evaluated by inhibiting cyclooxygenase-2 enzyme using TMPD Assay followed by an in silico study to validate their mechanism of action using celecoxib as a standard drug., Results: Compounds 4 , 6 and 8-10 exhibited potent anti- H. pylori activity with MIC values ranging from 0.48 to 1.95 µg/mL that were comparable to or more potent than clarithromycin. For COX-2 inhibitory assay, 4 , 7 and 8 revealed promising activities with IC 50 values of 1.04, 0.65 and 0.45 μg/mL, respectively. These results were verified by molecular docking studies, where 4 , 7 and 8 showed the best interactions with key amino acid residues of COX-2 active site., Conclusion: The present study characterizes a new sesquiterpene lactone and recommends 4 and 8 for future in vivo studies as plausible anti-ulcer remedies.

In this study, new benzothiazole-pyrimidine hybrids ( 5a - c , 6 , 7a - f , and 8 - 15 ) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound 4 were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains. The results indicated that compounds 5c , 5b , 12 , and 15 (MIC = 0.24-0.98 µg/mL) are highly active against the first-line drug-sensitive strain of Mycobacterium tuberculosis (ATCC 25177). Thereafter, the anti-tubercular activity was evaluated against the two drug-resistant TB strains; ATCC 35822 and RCMB 2674, where, many compounds exhibited good activity with MIC = 0.98-62.5 3 µg/mL and 3.9-62.5 µg/mL, respectively. Compounds 5c and 15 having the highest anti-tubercular efficiency towards sensitive strain, displayed the best activity for the resistant strains by showing the MIC = 0.98 and 1.95 µg/mL for MDR TB, and showing the MIC = 3.9 and 7.81 µg/mL for XDR TB, consecutively. Finally, molecular docking studies were performed for the two most active compounds 5c and 15 to explore their enzymatic inhibitory activities.

Objectives: This study aimed to assess compliance with legal requirements, safe medication storage and staffing standards in community pharmacies in Punjab, Pakistan., Method: We conducted a three-step cross-sectional study using observations, questionnaires and face-to-face interviews in 544 systematically-selected community pharmacies. We used descriptive statistic and one-way ANOVA to assess the data., Results: Only 23 (4.2 %) pharmacies had accurate area and only 3.9 % had appropriate walls. In total, 23.3 % had glass-fronted shelves and 38.2 % had a glass door. More than half (53.8 %) had separate narcotics shelves and 43.0 % a separate shelf of expired medicines. Less than half (47.5 %) of the pharmacies were able to maintain hygiene. About 36.2 % of the pharmacies segregated different types of product. Drugs were protected from direct sunlight in most (61.3 %) pharmacies, but the refrigerator was working properly in less than half (43.4 %) and only a very small number (2.4 %) had an alternative power supply for the refrigerator. Only 37 (6.8 %) were able to maintain an appropriate room temperature. The vast majority (93.0 %) displayed a valid drug sale license, but a qualified person/pharmacist was only present in 4.8 %. The average number of employees was 4.2, and more than 71.0 % of staff had 10-12 years of formal education. Only 0.2 % of employees could explain term "PRN", although 57.3 % explained "IV" correctly. About 22.8 % replied correctly about the room temperature but the vast majority (97.6 %) did not know about cold chain temperature. The location of the pharmacy ( p -value = 0.045) affected its performance., Conclusions: Noncompliance with legal requirements, unsafe drug storage and limited human resources reflect the poor enforcement of drug laws in Pakistan. The findings suggest that there is a need to strengthen inspection and management of community pharmacies., 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 The Authors.)

Holoptelea integrifolia , also known as the Indian Elm Tree, has been used in Ayurvedic medicine for its medicinal properties. In this study, two biologically active metabolites, 5(6) dihydrostigmast 22en 3- O -β-glucoside (DHS) and 1- O -eicosanoyl glycerol-2'- O -β-galactouronic (EGG), were isolated for the first time from the n -butanol fraction of H. integrifolia using a chromatographic technique and identified by NMR, and HRESI-MS. The antiviral and multidrug-resistant activities of these metabolites were evaluated as well as the n -butanol fraction. The n -butanol fraction of H. integrifolia exhibited weak antiviral effects, but DHS and EGG demonstrated significant antiviral activity against herpes simplex type-1 (HSV-1) and Coxsackie (CoxB4) viruses. Both metabolites showed lower IC 50 values than the standard antiviral drug acyclovir, indicating their potency in inhibiting viral replication. EGG showed potent antiviral activity with minimal cytotoxicity at the highest concentration tested, presenting a selectivity index (SI) of 18.18 and 15.58 against HSV-1 and CoxB4 viruses, respectively. A preliminary assessment of the antibacterial activity of the n -butanol fraction and metabolites revealed that DHS had the highest inhibitory potency against drug-resistant strains, including MRSA and Carbapenem-resistant Klebsiella pneumonia . It also exhibited significant inhibitions against Fluconazole-resistant Candida albicans and ESBL - Escherichia coli . DHS displayed the lowest minimum inhibitory concentration (MIC) values, indicating its superiority as an antibacterial agent compared to EGG and the n -butanol fraction. Molecular docking analysis confirmed the antiviral and antibacterial actions of DHS and EGG by demonstrating their strong binding., Competing Interests: The authors certify that this publication does not include any conflicts of 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., (This journal is © The Royal Society of Chemistry.)

Objective: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats., Materials and Methods:   A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract).  Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract., Results: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity., Conclusions: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.

Gouty arthritis is one of the most common metabolic disorders affecting people. Plant based drugs can lower the risk of this health disorder. The anti-gouty potential of Eucalyptus torquata flowers methanol extract (ETME) was evaluated in vitro via measuring the inhibitory effects of five pro-inflammatory enzymes; xanthine oxidase (XO), hyaluronidase, lipoxygenase (5-LOX), cyclooxygenases COX-1, and COX-2, in addition to evaluating the inhibition of histamine release, albumin denaturation, membrane stabilization, tyrosinase, and protease inhibitory activities. Also, its antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays and ferric reducing power assay (FRAP). HPLC-PDA-MS/MS was used to identify the metabolites in the tested extract. The latter exhibited substantial anti-arthritic properties in all assays with comparable potential to the corresponding reference drugs. HPLC-MS/MS analysis of this bioactive extract tentatively annotated 46 metabolites including phloroglucinols, gallic and ellagic acids derivatives, terpenes, flavonoids, fatty acids, and miscellaneous metabolites. Our study highlights the medicinal importance of E. torquata as an anti-gouty candidate and opens new avenues of gouty management., (© 2023. The Author(s).)

Background: Provider bias is a main barrier that extensively violates the right of free family planning method choice. Egypt is one of the countries that shows skewness in its method mix. Provider bias and insufficiency of alternative methods are identified as potential factors underlying this phenomenon which contributes to high unmet needs and discontinuation rates. Provider bias may be influenced by cultural beliefs and societal trends and is usually overlooked as a possible cause of this skewed method mix. This study aims to explore the presence of provider bias in rural Upper Egypt and its potential causes, a community with conservative cultural beliefs and least contraceptive prevalence rates., Methods: This is a qualitative study using the "simulated client's approach." The study was conducted in 16 villages in Assiut and Sohag governorates in Egypt. The simulated clients visited 30 clinics, 15 in each governorate, including primary healthcare units and private clinics. Three scenarios were used to explore the physicians-imposed restrictions for contraceptive use with different clients' eligibility criteria. Data was analyzed using the grounded theory methodology., Results: Recommending a contraceptive method for the mystery clients was not based on informed choice. Most providers had method or client bias. Copper IUD was the most favorable contraceptive method recommended by providers, with negative attitude towards using hormonal contraception. Nulliparous and young clients were discouraged to use contraception before proving fertility or offered temporary methods as emergency contraception or condoms. Providers have shown misconceptions related to infertility-associated complications of contraceptive use, especially for the young and nulliparous women., Conclusion: In this study, providers had a clear bias towards recommending IUD rather than all other contraceptive methods, which was hindered in some cases by the lack of insertion skills. Interventions to reduce provider bias should go beyond technical training. Moreover, training on reproductive rights should be a main component of routine training. Providers should regularly receive research results and be oriented toward recent medical eligibility criteria of contraceptive methods use. Moreover, the sociocultural beliefs of providers that may affect their practice should be explored and addressed., (© 2023. Egyptian Public Health Association.)

The research's goal is to create the surfaces of titanium dioxide nanoparticles (TiO 2 NPs) in a layer of folic acid (FA) that can effectively target human bladder cancer cells (T24). An efficient method for creating FA-coated TiO 2 NPs was used, and many tools have been used to analyze its physicochemical properties. The cytotoxic effects of FA-coated NPs on T24 cells and the mechanisms of apoptosis generation were examined employing a variety of methodologies. The prepared FA-coated TiO 2 NPs suspensions with a hydrodynamic diameter around 37 nm and a negative surface charge of -30 mV reduced T24 cell proliferation with stronger IC 50 value (21.8 ± 1.9 μg/ml) than TiO 2 NPs (47.8 ± 2.5 μg/ml). This toxicity resulted in apoptosis induction (16.63%) that was caused through enhanced reactive oxygen species formation and stopping the cell cycle over G2/M phase. Moreover, FA-TiO 2 NPs raised the expression levels of P53, P21, BCL2L4, and cleaved Caspase-3, while decreasing Bcl-2, Cyclin B, and CDK1 in treated cells. Overall, these findings revealed efficient targeting of the FA-TiO 2 NPs resulted in increasing cellular internalization caused increased apoptosis in T24 cells. As a result, FA-TiO 2 NPs might be a viable treatment for human bladder cancer., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

Medical video watermarking is one of the beneficial and efficient tools to prohibit important patients' data from illicit enrollment and redistribution. In this paper, a new blind watermarking scheme has been proposed to improve the confidentiality, integrity, authenticity, and perceptual quality of a medical video with minimum distortion. The proposed scheme is based on 2D-DWT and dual Hessenberg-QR decomposition, where the input medical video is initially processed into frames. Then, the processed frames are transformed into sub-bands using 2D-DWT, followed by applying Hessenberg-QR decomposition on the selected wavelet HL2 sub-band. The watermark is scrambled via Arnold cat map to raise confidentiality and then concealed in the modified selected features. The watermark is extracted in a fully blind mode without referencing the original video, which reduces the extraction time. The proposed scheme maintained a fundamental tradeoff between robustness and visual imperceptibility compared to existing methods against many commonly encountered attacks. The visual imperceptibility has been evaluated using well-known metrics PSNR, SSIM, Q-index, and histogram analysis. The proposed scheme achieves a high PSNR value of (70.6899 dB) with minimal distortion and a high robustness level with an average NC value of (0.9998) and BER value of (0.0023) while conserving a large payload capacity. The obtained results show superior performance over similar video watermarking methods. The limitation of this scheme is the elapsed time during the embedding process since we utilized dual Hessenberg-QR decomposition. One possible solution to reduce time consumption is simple decompositions like bound-constrained SVM or similar decompositions., 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 The Authors.)

Objectives: Few studies examined the analgesic effects of dexamethasone in lumbar paravertebral block, specifically the transincisional approach. This study aimed to compare dexamethasone with bupivacaine versus bupivacaine alone for bilateral transincisional paravertebral block (TiPVB) for postoperative analgesia in lumbar spine surgeries., Materials and Methods: Fifty patients who were aged 20 to 60 years and had American Society of Anesthesiologists Physical Status (ASA-PS) I or II of either sex were randomly allocated into 2 equal groups. Both groups received combined general anesthesia and bilateral lumbar TiPVB. However, in group 1 (dexamethasone group) (n=25), patients received 14 mL of bupivacaine 0.20% plus 1 mL containing 4 mg of dexamethasone on each side, while, in group 2 (control group) (n=25), patients received 14 mL of bupivacaine 0.20% plus 1 mL of saline on each side. Time to first analgesic need was the primary outcome, while total opioid consumption during the first 24 hours after surgery, the Visual Analog Scale for pain perception (0-10), and the incidence of side effects were secondary outcomes., Results: The mean time to the first analgesic requirement was significantly prolonged among patients in the dexamethasone group than the control group (mean±SD: 18.4±0.8 vs. 8.7±1.2 h, respectively) ( P <0.001). Patients in the dexamethasone group had lower total opiates consumption than the control) P <0.001). Although nonsignificant, the incidence of postoperative nausea and vomiting was more frequent among the control group ( P =0.145)., Discussion: Adding dexamethasone to bupivacaine in TiPVB resulted in a prolonged analgesia-free period and lower opioid consumption in lumbar spine surgeries with comparable incidence of adverse events., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC 50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and 3.9 µg/mL, respectively). Molecular docking studies suggest that this compound binds through the use of relatively unexplored hydrophobic pocket in the active site. Molecular dynamics was used to investigate and support the stability of 4l complex with the target enzyme. This study paves the way for the design and synthesis of novel antitubercular drugs., 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 © 2023 Elsevier Inc. All rights reserved.)

Two novel chemically cross-linked chitosan hydrogels were successfully prepared via insertion of oxalyl dihydrazide moieties between chitosan Schiff's base chains (OCsSB) and between chitosan chains (OCs). For more modification, two different concentrations of ZnO nanoparticles (ZnONPs) were loaded into OCs to obtain OCs/ZnONPs-1 % and OCs/ZnONPs-3 % composites. The prepared samples were recognized using elemental analyses, FTIR, XRD, SEM, EDS and TEM. Their inhibitory action against microbes and biofilms were classified as: OCs/ZnONPs-3 % > OCs/ZnONPs-1 % > OCs > OCsSB > chitosan. OCs has inhibition activity similar to Vancomycin of minimum inhibitory concentration (MIC) value of 3.9 μg/mL against P. aeruginosa. OCs exhibited minimum biofilm inhibitory concentration (MBIC) values (from 31.25 to 62.5 μg/mL) less than that of OCsSB (from 62.5 to 250 μg/mL) which lower than that of chitosan (from 500 to 1000 μg/mL) against S. epidermidis, P. aeruginosa and C. albicans. OCs/ZnNPs-3 % showed MIC value (that caused 100 % inhibition of Clostridioides difficile, C. difficile) of 0.48 μg/mL much lower than Vancomycin (1.95 μg/mL). Both OCs and OCs/ZnONPs-3 % composite were safe on normal human cells. Thus, inclusion of oxalyl dihydrazide and ZnONPs into chitosan greatly reinforced its antimicrobial activity. This is a good strategy to accomplish adequate systems for competing traditional antibiotics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The development of novel antimycobacterial agents is an urgent challenge to eradicate the increasing emergence and rapid spread of multidrug-resistant strains. Filamentous temperature-sensitive protein Z (FtsZ) is a crucial cell division protein. Alteration of FtsZ assembly leads to cell division inhibition and cell death. To find novel antimycobacterial agents, a series of N 1 -(benzo[d]oxazol-2-yl)-N 4 -arylidine compounds 5a-o were synthesized. The activity of the compounds was evaluated against drug-sensitive, multidrug-resistant, and extensive-drug-resistant Mycobacterium tuberculosis. Compounds 5b, 5c, 5l, 5m, and 5o showed promising antimycobacterial activity with minimum inhibitory concentrations (MIC) in the range of 0.48-1.85 µg/mL and with low cytotoxicity against human nontumorigenic lung fibroblast WI-38 cells. The activity of the compounds 5b, 5c, 5l, 5m, and 5o was evaluated against bronchitis causing-bacteria. They exhibited good activity against Streptococcus pneumoniae, Klebsiella pneumoniae, Mycoplasma pneumonia, and Bordetella pertussis. Molecular dynamics simulations of Mtb FtsZ protein-ligand complexes identified the interdomain site as the binding site and key interactions. ADME prediction indicated that the synthesized compounds have drug-likeness. The density function theory studies of 5c, 5l, and 5n were performed to investigate E/Z isomerization. Compounds 5c and 5l are present as E-isomers and 5n as an E/Z mixture. Our experimental outcomes provide an auspicious lead for the design of more selective and potent antimycobacterial drugs., (© 2023 Deutsche Pharmazeutische Gesellschaft.)