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Coronavirus disease-19 emerged in December 2019. Healthcare workers were exposed to this highly infectious virus during the pandemic and suffered several social and psychological consequences, such as anxiety, psychological distress, and burnout. To assess the psychological distress, anxiety, depression, coping strategies, risk perception, and attitude toward interprofessional teamwork among Egyptian healthcare workers during the COVID-19 pandemic. We conducted a cross-sectional online survey which consisted of five sections. The primary outcomes were anxiety (GAD-7), depression (PHQ-9), risk perception towards COVID-19, interprofessional teamwork attitude, and coping strategies during the Coronavirus disease-19 pandemic. The web-based questionnaire was distributed to Egyptian healthcare workers from the 20th of April 2020 to the 20th of May 2020. A snowball sampling method was used. Regression analysis was conducted to test the relationship between the socioeconomic characteristics and the previously mentioned outcomes. A total of 403 participants responded to the online questionnaire. The majority were females (70.5%) and within the age group of 26-40 years (77.7%), with 2-5 years of work experience (43.2%). Most participants were pharmacists (33%) and physicians (22.1%). Eighty-two participants (21%) reported moderate to severe anxiety, and 79 participants reported (19.4%) moderate to severe depressive symptoms. In the univariate model, the marital status was associated with depression (OR 0.47, 95% CI 0.28-0.78), anxiety (OR 0.52, 95% CI 0.32-0.85), and an attitude toward interprofessional teamwork (β = -1.96 95% CI -2.72 to -1.2). Providing direct care to the patients was associated with lower anxiety symptoms (AOR 0.256, 95% CI 0.094-0.697). More severe anxiety and depressive symptoms were associated with difficulties in everyday life and the professional work environment (AOR 4.246 and 3.3, P = 0.003 and 0.01, respectively). Availability of mental health facilities at the workplace was associated with a lower risk perception towards COVID-19 (β = -0.79, 95% CI -1.24 to -0.34) and a more positive attitude towards teamwork (β = 2.77 95% CI 1.38-4.15). According to our results, the COVID-19 pandemic was associated with mild anxiety and depression among healthcare workers in Egypt, especially pharmacists and physicians. We recommend more research targeting the mental health of healthcare workers in Egypt. If proven cost-effective and needed, wide-scale mental health screening and public health campaigns can facilitate effective prevention and treatment strategies. In addition, the availability of mental health facilities at the workplace could alleviate some of the risk perception associated with health emergencies and improve interprofessional teamwork.

Freshwater shortages in the Middle East and North Africa's region (MENA) cause serious issues, while climate change causes even more issues. The current study examines how climate change may impact future irrigation requirements in Egypt's Upper Region using the medium greenhouse emission RCP 4.5 and high emission RCP 8.5 scenarios. Based on the Intergovernmental Panel on Climate Change (IPCC) and the Fifth Assessment Report, the climatic projections for RCPs 4.5 and 8.5 for the years 2023–2080 and 2081–2100 were used to determine the patterns of temperature and rainfall in the upper Egypt territory. The CROPWAT model was employed to estimate reference evapotranspiration (ET o ) and net irrigation water requirement (NIWR) for the upper Egypt territory key crops sugar cane, potatoes, berseem clover (alfalfa), dry bean, wheat, cotton, maize, and tomato based on the predicted meteorological conditions. Five different scenarios for the key crops' future irrigation needs were calculated. The results reveal that under RCP 4.5 greenhouse emission for the periods 2023–2080 and 2081–2100, respectively, the overall NIWR for all examined crops increases by 5.1 and 5.9% in comparison to the current (2022) total NIWR for all crops. The total NIWR for all crops analyzed increases by 7.7 and 9.7% under the RCP 8.5 greenhouse emission scenario for the periods 2023–2080 and 2081–2100, respectively, in contrast to the current total NIWR for all crops. It is important to consider changes in water resource management in the MENA region, such as applying modern irrigation systems, using crop pattern rotation strategies with minimal water demands, and changing crop calendars or the times and locations of cropping activities.

Background: Global population aging poses challenges for healthcare. Digital health technologies may benefit older adults through enhanced access, monitoring, and self-care. This systematic review evaluates the intersection of digital health interventions and healthy aging, focusing on adoption, efficacy, and user experience. Methods: PubMed, Embase, and Cochrane Library were systematically searched for studies on digital health technologies for adults aged 50+ years. Randomized controlled trials, observational studies, surveys, and qualitative studies were included. Outcomes were adoption rates, efficacy, and qualitative feedback. Study quality was assessed using standardized tools. Results: 15 studies were included. Adoption increased during COVID-19, but divisions persist. Barriers like technology challenges and distrust require addressing. Web-based programs and telerehabilitation demonstrated benefits for behaviors and balance. Users had positive attitudes but emphasized patient-centric, ethical design. Most efficacy data were preliminary; more rigorous trials are needed. Discussion: Digital health interventions show promise for supporting healthy aging, but thoughtful implementation strategies tailored to user needs and capacities are essential to realizing benefits equitably. More efficacy research and studies on real-world integration and ethics are warranted. Conclusions: Digital health has significant potential for promoting healthy aging through enhanced access, monitoring, and self-care. However, evidence-based, patient-centered solutions are imperative to maximize adoption, efficacy, and positive user experience for diverse older adult populations.

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the surface of G5 molecules via two different enzyme-sensitive linkages, L3 or L4, to achieve controllable drug release inside hepatic cancer cells. We previously reported on P1 and P2 particles that resulted from the combination of NAcGal-targeting with L3- or L4-DOX linkages, respectively, and showed controllable DOX release and toxicity towards hepatic cancer cells comparable to free DOX. In this study, we demonstrate that while the intratumoral delivery of free DOX (1 mg/kg) into HCC-bearing nod scid gamma (NSG) mice achieves a 2.5-fold inhibition of tumor growth compared to the saline group over 30 days, P1 and P2 particles delivered at the same DOX dosage achieve a 5.1- and 4.4-fold inhibition, respectively. Incubation of the particles with human induced pluripotent stem cell derived cardiomyocytes (hiPSC CMs) showed no effect on monolayer viability, apoptosis induction, or CM electrophysiology, contrary to the effect of free DOX. Moreover, magnetic resonance imaging revealed that P1- and P2-treated mice maintained cardiac function after intraperitoneal administration of DOX at 1 mg/kg for 21 days, unlike the free DOX group at an equivalent dosage, confirming that P1/P2 can avoid DOX-induced cardiotoxicity. Taken together, these results highlight the ability of P1/P2 particles to improve the therapeutic index of DOX and offer a replacement therapy for clinical HCC treatment.

In all organs, control of blood flow is important but might be particularly critical for testicular functions. This is because of the very low oxygen concentration and high metabolic rate of the seminiferous tubules, the physiological temperature of the testis, and its location outside the abdominal cavity. Many factors affect the characteristics of TBF in farm and companion animals, such as environment (thermal and seasonal effects) and physiological (species, breeds, age, body weight, and sexual maturity). Thermal environment stress has detrimental effects on spermatogenesis and consequently has more serious impacts on both human and animal fertility. Numerous studies have been performed to assess TBF in different animal species including bulls, rams, bucks, alpacas, stallions, and dogs with varied results. Hence, assessment of TBF by Doppler ultrasonography is of great importance to estimate the effect of high environment temperature on testicular functions. Also, differences observed in the TBF may result from different technical aspects such as the identification of the segment of the testicular artery to be examined. In the current review, we focused on the imperative roles of TBF in various animal species. Besides, we discussed in detail various factors that could affect TBF. These factors can significantly modify the TBF and thus should be considered when establishing reference values in farm animals for better clinical diagnosis. The information provided in this review is valuable for researchers and veterinarians to help them a better understanding of testicular hemodynamics for the proper evaluation of breeding soundness examination in males.

Pseudomonas aeruginosa ( P. aeruginosa ) is an opportunistic bacterium that is widely distributed in aquatic environments and causes major economic losses in fish and public health hazards.This study aimed to identify the occurrence of P. aeruginosa in samples collected from fish and fish handlers, and to investigate the antimicrobial susceptibility, virulence determinants, and biofilm genes of P. aeruginosa isolates. A total of 276 samples were cross-sectionally collected from Nile tilapia (53), Golden grey mullet (52), Mediterranean horse mackerel (50), Striped red mullet (71), and fish handlers (50) at five different retail fish markets in Damietta Governorate, Egypt. Pseudomonas species (spp.) were biochemically identified in 57.9% of the total examined samples. Peudomonas aeruginosa were the most prevalent species isolated from the fish and human samples via PCR technique. Peudomonas aeruginosa isolates exhibited full resistance (100%) to tobramycin (TOB), gentamicin (CN), and colistin (CL), with a high level of susceptibility (88.5%) to imipenem (IPM) using the disk diffusion method. Most P. aeruginosa isolates (84.6%) exhibited drug resistance, with 61.5% were multidrug resistance (MDR) and 23.1% were extensive drug resistance (XDR). Most isolates had at least four virulence-associated genes ( las B, tox A, exo U, and opr L) and three biofilm genes ( psI A, peI A, and las R) by using uniplex PCR. The las I, and rhl R Quorum Sensing (QS) genes were identified in 84.6% and 61.5% in the examined P. aeruginosa isolates, respectively. The highest mortality rate in Nile tilapia experimentally infected with P. aeruginosa isolate encoding most of virulent genes. Multivariate analyses revealed high heterogeneity among the examined isolates. This study revealed the emergence of virulent and drug resistant P. aeruginosa isolates in fish, poses high risks to consumers and food. Thus, strict hygienic measures should be considered when catching, handling, and storing fish, in addition to the routine application of antimicrobial susceptibility testing.

In this article, a novel type of equation, namely the Φ-Hilfer fractional-order integro-differential delay system (Φ-HFOIDDS), is proposed. Here, we study the existence and Hyers–Ulam–Mittag–Leffler (H-U-M-L) stability of the aforementioned equation which are obtained by using the multivariate Mittag–Leffler function, Banach contraction principle, and Picard operator method as well as generalized Gronwall inequality. Finally, we conclude this paper by constructing a suitable example to illustrate the applicability of the principal outcomes.

The rate of microbial resistance has continued to rise significantly as the availability of new antibiotics has declined. A new series of pyridine and thienopyridine derivatives were designed, synthesized and tested as antimicrobial agents. The reaction of 4-bromo acetophenone and vetraldehyde (3,4-dimethoxy benzaldehyde) in ethanol and sodium hydroxide solution afforded the corresponding chalcone which was used as a suitable precursor to prepare a new series of pyridine derivatives. The treatment of the latter chalcone with 2-cyanothioacetamide afforded the corresponding pyridinethione which was used as a precursor to synthesize the targeted thienopyridine derivatives in good to excellent yield by the reaction with 2-chloro- N -arylacetamide derivatives, α-haloketones, methyl iodide or chloroacetonitrile in one or two steps. The structure of the synthesized compounds was confirmed chemically by their preparations with other pathways and their spectral data. The newly synthesized pyridine and thienopyridine derivatives exhibited good to strong antimicrobial activity against microbial strains E. coli , B. mycoides and C. albicans . With maximal antimicrobial activity against B. mycoides (33 mm) and C. albicans (29 mm), respectively, compounds 12a and 15 demonstrated the highest inhibition zone. Compound 12a prevented the growth of E. coli , at MIC level of 0.0195 mg/mL, and B. mycoides and C. albicans at MIC level below than 0.0048 mg/mL, respectively. Additionally, compound 15 prevented the visible growth of E. coli , B. mycoides , and C. albicans at MIC values of >0.0048, 0.0098, and 0.039 mg/mL, respectively. The relation between the chemical structure of the synthesized pyridine and thienopyridine compounds and their antimicrobial properties was discussed in the SAR study.

Toxicity from the external presence or internal production of compounds can reduce the growth and viability of microbial cell factories and compromise productivity. Aromatic compounds are generally toxic for microorganisms, which makes their production in microbial hosts challenging. Here we use adaptive laboratory evolution to generate Saccharomyces cerevisiae mutants tolerant to two aromatic acids, coumaric acid and ferulic acid. The evolution experiments were performed at low pH (3.5) to reproduce conditions typical of industrial processes. Mutant strains tolerant to levels of aromatic acids near the solubility limit were then analyzed by whole genome sequencing, which revealed prevalent point mutations in a transcriptional activator (Aro80) that is responsible for regulating the use of aromatic amino acids as the nitrogen source. Among the genes regulated by Aro80, ESBP6 was found to be responsible for increasing tolerance to aromatic acids by exporting them out of the cell. Further examination of the native function of Esbp6 revealed that this transporter can excrete fusel acids (byproducts of aromatic amino acid catabolism) and this role is shared with at least one additional transporter native to S. cerevisiae (Pdr12). Besides conferring tolerance to aromatic acids, ESBP6 overexpression was also shown to significantly improve the secretion in coumaric acid production strains. Overall, we showed that regulating the activity of transporters is a major mechanism to improve tolerance to aromatic acids. These findings can be used to modulate the intracellular concentration of aromatic compounds to optimize the excretion of such products while keeping precursor molecules inside the cell.

Purpose Oral delivery of therapeutic peptides has been challenging due to multiple physiological factors and physicochemical properties of peptides. We report a systematic approach to identify formulation compositions combining a permeation enhancer and a peptidase inhibitor that minimize proteolytic degradation and increase absorption of a peptide across the small intestine. Methods An acylated glucagon-like peptide-1/glucagon co-agonist peptide (4.5 kDa) was selected as a model peptide. Proteolytic stability of the peptide was investigated in rat and pig SIF. Effective PEs and multiple component formulations were identified in rats. Relative bioavailability of the peptide was determined in minipigs via intraduodenal administration (ID) of enteric capsules. Results The peptide degraded rapidly in the rat and pig SIF. Citric acid, SBTI, and SBTCI inhibited the enzymatic degradation. The peptide self-associated into trimers in solution, however, addition of PEs monomerized the peptide. C10 was the most effective PE among tested PEs (DPC, LC, rhamnolipid, C12-maltosides, and SNAC) to improve intestinal absorption of the peptide in the rat IJ-closed loop model. A combination of C10 and SBTI or SBTCI increased the peptide exposure 5–tenfold compared to the exposure with the PE alone in the rat IJ-cannulated model, and achieved 1.06 ± 0.76% bioavailability in minipigs relative to subcutaneous via ID administration using enteric capsules. Conclusion We identified SBTI and C10 as an effective peptidase inhibitor and PE for intestinal absorption of the peptide. The combination of SBTI and C10 addressed the peptide physiochemical properties and provides a formulation strategy to achieve intestinal delivery of this peptide.