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Understanding the genetic causes of diseases that affect pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy, and diabetes syndrome (MEDS) is a congenital disorder with two known etiological genes, IER3IP1 and YIPF5. Both genes encode proteins involved in endoplasmic reticulum (ER) to Golgi trafficking. We used genome sequencing to identify 6 individuals with MEDS caused by biallelic variants in the potentially novel disease gene TMEM167A. All had neonatal diabetes (diagnosed at <6 months) and severe microcephaly, and 5 also had epilepsy. TMEM167A is highly expressed in developing and adult human pancreas and brain. To gain insights into the mechanisms leading to diabetes, we silenced TMEM167A in EndoC-βH1 cells and knocked-in one patient's variant, p.Val59Glu, in induced pluripotent stem cells (iPSCs). Both TMEM167A depletion in EndoC-βH1 cells and the p.Val59Glu variant in iPSC-derived β cells sensitized β cells to ER stress. The p.Val59Glu variant impaired proinsulin trafficking to the Golgi and induced iPSC-β cell dysfunction. The discovery of TMEM167A variants as a genetic cause of MEDS highlights a critical role of TMEM167A in the ER to Golgi pathway in β cells and neurons.

Fibromyalgia (FM) is a common rheumatic illness distinguished by chronic pain, fatigue, cognitive problems, and functional disability. However, the differences between men and women have not yet been comprehensively studied, especially after the development of the last 2016 American College of Rheumatology (ACR) criteria. The aim of this study was to evaluate the gender differences in symptom characteristics, cognitive dysfunction, and disease severity in Egyptian FM patients considering both the ACR 1990, 2011, and the last 2016 ACR diagnostic criteria. This is a prospective cross-sectional study that was carried out on 352 patients with FM in the Rheumatology Department, Al-Azhar University Hospital in Egypt, in the period between January 1, 2020, and June 1, 2021. In addition to the number of tender points (TPC), data was collected on age, gender, body mass index (BMI), marital status, disease onset, duration, and diagnostic delay. The widespread pain index (WPI), the symptom severity scale (SSS), fatigue, cognitive dysfunction, sleep disturbance, awakening unrefreshed, headache, abdominal pain, and depression were evaluated and scored according to 2010 and 2016 ACR criteria. A visual analog scale (VAS) for pain, fatigue, stiffness, anxiety, and depression is included in the questionnaire. The total score ranges were produced using total score ranges ranging from 0 to 80 (excluding job items), with higher scores indicating a stronger negative effect and/or intensity of symptoms. The polysymptomatic distress scale (PDS) has been calculated by the summation of the SSS with the WPI. The Revised FM impact questionnaire (FIQR) has also been evaluated. The study shows that females have a significantly higher prevalence of fatigue, cognitive dysfunction, sleep disturbance, headache, and abdominal pain (p < 0.05). Also, females showed significantly higher scores than males regarding WPI, SSS, and mean TPC (p = 0.004, 0.027, and 0.001, respectively). While there was no difference regarding the FIQR (p=0.93), PDS was significantly higher in women (p= 0.001). Female patients with FM had greater disease severity scores, symptomatology, and number of tender points. Whatever the criteria applied, the prevalence and intensity of the disease features are higher in females, which may underestimate the disease in male patients.

Background Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans . New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). Objectives This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. Methods The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. Results Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. Conclusion The current findings highlight FA’s potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Diabetic foot ulcers are recognized to be a severe complication of diabetes, increasing the risk of amputation and death. The bacterial infection of Diabetic foot ulcers with virulent and resistant bacteria as Proteus mirabilis greatly worsens the wound and may not be treated with conventional therapeutics. Developing new approaches to target bacterial virulence can be helpful to conquer such infections. In the current work, we evaluated the anti-virulence activities of the widely used antibacterial metronidazole. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MEBC) were determined for selected antibiotics which P. mirabilis was resistant to them in the presence and absence of metronidazole in sub-MIC. The effect of metronidazole in sub-MIC on P. mirabilis virulence factors as production of exoenzymes, motilities, adhesion and biofilm formation, were evaluated. Furthermore, molecular docking of metronidazole into P. mirabilis adhesion and essential quorum sensing (QS) proteins, was performed. The results revealed a significant ability of metronidazole to in-vitro inhibit P. mirabilis virulence factors and antagonize its essential proteins. Moreover, metronidazole markedly decreased the MICs and MBECs of tested antibiotics. Conclusively, metronidazole in sub-MIC is a plausible anti-virulence and anti-QS agent that can be combined to other antibiotics as anti-virulence adjuvant to defeat aggressive infections.

The development of resistance to carbapenems in Klebsiella pneumoniae due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing K. pneumoniae . Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant K. pneumoniae isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes bla NDM and bla VIM . A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing K. pneumoniae .

Familial dyslipidemia (FD), particularly familial hypercholesterolemia (FH), is a major contributor to premature cardiovascular disease (CVD), especially in regions with high consanguinity and underutilized genetic screening, such as Egypt. This study aimed to assess clinical, biochemical, and genetic factors that differentiate FD patients with and without CVD, and to develop a composite risk score for individualized stratification. A cross-sectional study was conducted on 60 Egyptian patients aged 15–25 years with genetically confirmed FD, equally divided based on CVD status. All participants underwent detailed clinical assessment, lipid profiling, and targeted next-generation sequencing of LDLR, APOB, and PCSK9 genes. Missense variants were evaluated using SIFT, PolyPhen-2, CADD, and ΔΔG stability scores, and classified according to ACMG criteria. Compared to non-CVD patients, those with CVD had significantly higher triglyceride levels (median: 356.5 vs. 236.5 mg/dL; p < 0.001) and a higher frequency of heterozygous pathogenic LDLR variants (30.0% vs. 3.3%; p = 0.006), while homozygous variants were more common in non-CVD patients (26.7% vs. 0%; p = 0.002). Deleterious missense variants were notably more frequent in the CVD group (56.7% vs. 10.0%; p < 0.001). A 10-variable composite risk score integrating clinical, lipid, and bioinformatic predictors effectively distinguished high- and moderate-risk cases (AUC = 0.742; p = 0.022), with 89.5% sensitivity and 81.8% negative predictive value. The study highlights the importance of combining clinical and genomic data for early risk stratification and introduces a pragmatic tool for identifying high-risk youth in resource-limited, consanguineous populations.

The agricultural domain in developing countries is mostly dictated by archaic rules based on traditions and inherited practices. With the evolution of digitalization and technology, it seems essential to apply new technologies to the agricultural field. Among the technologies to be exploited in agriculture, we mention sensors, IoT, WSN, cloud, blockchain, etc. We talk about smart agriculture in this case. In this paper, we propose a platform secured by blockchain for monitoring and securing production. This platform uses IoT connected sensors to track and save data. Our system is used to monitor the production process of olive trees. The goal is to track everything that enters and leaves our olive tree production from fertilizers, insecticides, and fortifiers to olives, trimming etc. The blockchain via its decentralized system allow a secure, irreversible, and clear monitoring. A dashboard allow us to highlight the changes while facilitating the work of farmers. Our prototype will be embedded via a Raspberry Pi 4 platform.

The present study analyses plant diversity and evaluates the relationship between edaphic variables and the distribution and grouping of plant species in the Aswan Reservoir area, South Egypt. The dominant families were Fabaceae, Poaceae, and Asteraceae, forming 38.82% of the total flora recorded. The main bulk of the flora recorded (50.59%) belonged to the cosmopolitan, neotropical, pantropical, and palaeotropical chorotypes. A TWINSPAN analysis produced 10 vegetation clusters. Inundation levels showed a high correlation with species richness. The seasonally inundated area in Bute El-Hasaya and Maezana Belal (cluster V) had the highest species richness (36.50), while the lowest species richness (4.50) was in the shoreline of Philae, Awad, and Heisa islands (cluster IX). The DCA ordination depicted the environmental gradient expressed by the cluster analysis, and the resulting vegetation groups represented a distinct microhabitat. The CCA ordination indicates that the separation of vegetation group (A) along the axis was affected by the concentration of K, Mg, and CO3, and the vegetation group (B) was significantly associated with the total dissolved salts and the concentration of Cl. Moreover, the vegetation group (C) correlated significantly with pH, electrical conductivity, organic matter content, and SO3, HCO3, PO4, Na, and Ca concentrations.

Background. Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection, platelet-rich plasma (PRP) injection, and extracorporeal shock wave therapy (ESWT) as different modalities to alleviate pain and enhance function in patients with pes anserine bursitis (PAB). Methods. A prospective, randomized, comparative study was conducted on 180 patients diagnosed with chronic PAB. They were equally divided into three groups as follows: Group I received a local corticosteroid injection of 40 mg of methylprednisolone acetate/1 ml; Group II received a PRP injection; and in Group III, ESWT was used. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) pain score, WOMAC physical function score, and Ritchie articular index (RAI) for tenderness, which were recorded at the baseline, after 1 week, and after 8 weeks. Results. Before the application of procedures, there was a statistically significant increase in the WOMAC pain score in the local corticosteroid group compared to the PRP group and the ESWT group (P<0.001). After the application of procedures, there was a statistically significant improvement in the 1-week and 8-week WOMAC pain score, WOMAC physical function score, and VAS in the local corticosteroid group in comparison to the PRP group and the ESWT group. (P<0.001). Moreover, RAI for tenderness shows statistically significant improvement at 8 weeks in the local corticosteroid groups compared to the PRP groups (P<0.001) and ESWT groups (P<0.001). Similarly, a statistically significant difference was found between the PRP and ESWT groups (P=0.023). Conclusion. Our data suggest that in patients with PAB, local corticosteroid injection is more efficient than PRP injection and ESWT for reducing pain and enhancing function.

Bacteria communicate with each other using quorum sensing (QS) which works in an inducer/receptor manner. QS plays the main role in orchestrating diverse bacterial virulence factors. Pseudomonas aeruginosa is one of the most clinically important bacterial pathogens that can cause infection in almost all body tissues. Besides its efficient capability to develop resistance to different antibiotics, P. aeruginosa acquires a huge arsenal of virulence factors that are controlled mainly by QS. Challenging QS with FDA-approved drugs and natural products was proposed as a promising approach to mitigate bacterial virulence enabling the host immunity to complete the eradication of bacterial infection. The present study aims to evaluate the dipeptidase inhibitor-4 inhibitor hypoglycemic linagliptin anti-QS and anti-virulence activities against P. aeruginosa in vitro, in vivo, and in silico. The current results revealed the significant ability to diminish the production of protease and pyocyanin, motility, and biofilm formation in P. aeruginosa. Furthermore, the histopathological examination of liver and kidney tissues of mice injected with linagliptin-treated bacteria showed an obvious reduction of pathogenesis. Linagliptin downregulation to QS-encoding genes, besides the virtual ability to interact with QS receptors, indicates its anti-QS activities. In conclusion, linagliptin is a promising anti-virulence and anti-QS candidate that can be used solely or in combination with traditional antimicrobial agents in the treatment of P. aeruginosa aggressive infections.