Dual Drug-Loaded Coaxial Nanofiber Dressings for the Treatment of Diabetic Foot Ulcer.

Introduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization. Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds. Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups. Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.

Trimethoprim-sulfamethoxazole versus levofloxacin for the treatment of Stenotrophomonas maltophilia infections: A multicenter cohort study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged as a potential option for treating these infections. This study aimed to evaluate the clinical outcomes in patients who received TMP-SMX versus levofloxacin for treating S. maltophilia infections. METHOD: A retrospective, cohort study was conducted in 4 tertiary centers and included patients who were treated with either TMP-SMX or levofloxacin for infections caused by S. maltophilia. The main study outcomes were overall in-hospital mortality, 30-day mortality, and clinical cure. Safety outcomes were also evaluated. Multivariate analysis using logistic regression was used to control for the effect of the covariables. RESULTS: We included 371 patients in this study, 316 received TMP-SMX and 55 patients received levofloxacin. A total of 70% were in the intensive care unit and 21% presented with bacteremia. No statistically significant differences were observed in overall in-hospital mortality (52% vs 40%; p = 0.113; OR, 1.59; 95% CI, 0.89-2.86), 30-day mortality (28% vs 25%; p = 0.712; OR, 1.13; 95% CI, 0.59-2.18), or clinical cure (55% vs 64%; p = 0.237; OR, 0.70; 95% CI, 0.37-1.31). Rates of acute kidney injury were comparable between the two groups (11% vs 7%; p = 0.413). CONCLUSION: Patients receiving levofloxacin for the treatment of infections caused by S. maltophilia demonstrated clinical outcomes similar to those receiving TMP-SMX. Our study suggests that levofloxacin can be a reasonable alternative to TMP-SMX to treat these infections.

Trend of pharmaceuticals 3D printing in the Middle East and North Africa (MENA) region: An overview, regulatory perspective and future outlook.

The traditional method of producing medicine using the "one-size fits all" model is becoming a major issue for pharmaceutical manufacturers due to its inability to produce customizable medicines for individuals' needs. Three-dimensional (3D) printing is a new disruptive technology that offers many benefits to the pharmaceutical industry by revolutionizing the way pharmaceuticals are developed and manufactured. 3D printing technology enables the on-demand production of personalized medicine with tailored dosage, shape and release characteristics. Despite the lack of clear regulatory guidance, there is substantial interest in adopting 3D printing technology in the large-scale manufacturing of medicine. This review aims to evaluate the research efforts of 3D printing technology in the Middle East and North Africa (MENA) region, with a particular emphasis on pharmaceutical research and development. Our analysis indicates an upsurge in the overall research activity of 3D printing technology but there is limited progress in pharmaceuticals research and development. While the MENA region still lags, there is evidence of the regional interest in expanding the 3D printing technology applications in different sectors including pharmaceuticals. 3D printing holds great promise for pharmaceutical development within the MENA region and its advancement will require a strong collaboration between academic researchers and industry partners in parallel with drafting detailed guidelines from regulatory authorities.

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing.

Background: Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. Rationale: In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. Results: The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. Conclusion: This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Epidemiology of Reportable Bacterial Infectious Diseases in Saudi Arabia.

INTRODUCTION: Bacterial infections have a significant impact on human health; they can cause severe morbidity and mortality, particularly in susceptible populations. Epidemiological surveillance is a critical tool for monitoring the population's health and facilitate the prevention and control of infectious disease outbreaks. Knowing the burden of bacterial communicable diseases is an initial core step toward public health goals. METHODS: Saudi epidemiology surveillance data were utilized to depict the changing epidemiology of bacterial infectious diseases in Saudi Arabia from 2018 to 2021. The cumulative numbers of cases, demographics, and incidence rates were analyzed and visualized. Parametric tests were used to compare the difference in the mean values between categorical variables. Regression analysis was employed to estimate trends in disease rates over time. Statistical significance was set at p value ≤ 0.05. RESULTS: The results revealed that brucellosis, tuberculosis, and salmonellosis were the most frequently reported bacterial infectious diseases in Saudi Arabia. Males were more significantly affected by brucellosis and tuberculosis infections than females. Salmonellosis infections were more significant among Saudi citizens, while pulmonary tuberculosis was more significant in non-Saudis. Interestingly, there was a decline in the incidence rates of numerous bacterial infectious diseases during the Coronavirus Disease 2019 (COVID-19) pandemic and COVID-19 restrictions. Some bacterial infectious diseases were rarely reported in Saudi Arabia, including syphilis and diphtheria. CONCLUSIONS: The future perspective of this research is to enhance disease surveillance reporting by including different variables, such as the source of infection, travel history, hospitalization, and mortality rates. The aim is to improve the sensitivity and specificity of surveillance data and focus on the mortality associated with bacterial pathogens to identify the most significant threats and set a public health priority.

Development of progesterone electrospun nanofibers to coat Arabin pessaries as a dual preventive and therapeutic approach for preterm labor.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

Mitochondrial DNA variation in Aedes aegypti (Diptera: Culicidae) mosquitoes from Jeddah, Saudi Arabia.

Wolbachia (Hertig 1936) (Rickettsiales: Ehrlichiaceae) has emerged as a valuable biocontrol tool in the fight against dengue by suppressing the transmission of the virus through mosquitoes. Monitoring the dynamics of Wolbachia is crucial for evaluating the effectiveness of release programs. Mitochondrial (mtDNA) markers serve as important tools for molecular tracking of infected mitochondrial backgrounds over time but require an understanding of the variation in release sites. In this study, we investigated the mitochondrial lineages of Aedes aegypti (Linnaeus 1762) in Jeddah, Saudi Arabia, which is a prospective release site for the "wAlbBQ" Wolbachia-infected strain of this mosquito species. We employed a combination of comprehensive mitogenomic analysis (including all protein-coding genes) and mtDNA marker analysis (cox1 and nad5) using data collected from Jeddah. We combined our mitogenome and mtDNA marker data with those from previous studies to place mitochondrial variation in Saudi Arabia into a broader global context. Our findings revealed the presence of 4 subclades that can be broadly categorized into 2 major mitochondrial lineages. Ae. aegypti mosquitoes from Jeddah belonged to both major lineages. Whilst mitogenomic data offered a higher resolution for distinguishing Jeddah mosquitoes from the wAlbBQ strain, the combination of cox1 and nad5 mtDNA markers alone proved to be sufficient. This study provides the first important characterization of Ae. aegypti mitochondrial lineages in Saudi Arabia and offers essential baseline information for planning future molecular monitoring efforts during the release of Wolbachia-infected mosquitoes.

Green Synthesis of Silver Nanoparticles Using Jacobaea maritima and the Evaluation of Their Antibacterial and Anticancer Activities.

Much attention has been gained on green silver nanoparticles (green-AgNPs) in the medical field due to their remarkable effects against multi-drug resistant (MDR) microorganisms and targeted cancer treatment. In the current study, we demonstrated a simple and environment-friendly (i.e., green) AgNP synthesis utilizing Jacobaea maritima aqueous leaf extract. This leaf is well-known for its medicinal properties and acts as a reducing and stabilizing agent. Nanoparticle preparation with the desired size and shape was controlled by distinct parameters; for instance, temperature, extract concentration of salt, and pH. The characterization of biosynthesized AgNPs was performed by the UV-spectroscopy technique, dynamic light scattering, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. The successful formation of AgNPs was confirmed by a surface plasmon resonance at 422 nm using UV-visible spectroscopy and color change observation with a particle size of 37± 10 nm and a zeta potential of -10.9 ± 2.3 mV. SEM further confirmed the spherical size and shape of AgNPs with a size varying from 28 to 52 nm. Antibacterial activity of the AgNPs was confirmed against all Gram-negative and Gram-positive bacterial reference and MDR strains that were used in different inhibitory rates, and the highest effect was on the E-coli reference strain (MIC = 25 µg/mL). The anticancer study of AgNPs exhibited an IC50 of 1.37 µg/mL and 1.98 µg/mL against MCF-7 (breast cancer cells) and A549 (lung cancer cells), respectively. Therefore, this green synthesis of AgNPs could have a potential clinical application, and further in vivo study is required to assess their safety and efficacy.

Evaluation of Xpert MTB/RIF Ultra for the Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in Saudi Arabia.

The incidence of extrapulmonary tuberculosis (EPTB) in low- and middle-income countries, as well as, high-income countries has increased over the last two decades. The acid-fast bacillus (AFB) smear test is easy to perform and cost-effective with a quick turnaround time but the test has low sensitivity. Culture remains the gold standard for detecting TB; however, it has low sensitivity and slow bacterial growth patterns, as it may take up to 6 to 8 weeks to grow. Therefore, a rapid detection tool is crucial for the early initiation of treatment and ensuring an improved therapeutic outcome. Here, the Xpert Ultra system was developed as a nucleic acid amplification technique to accelerate the detection of MTB in paucibacillary clinical samples and endorsed by the World Health Organization. From March 2020 to August 2021, Xpert Ultra was evaluated for its sensitivity and specificity against EPTB and compared with those of the routinely used Xpert, culture, and AFB tests in 845 clinical samples in Saudi Arabia. The results indicate the overall sensitivity and specificity of Xpert Ultra to be 91% and 95%, respectively, compared with the Xpert (82% and 99%, respectively) and AFB smear (18% and 100%, respectively) tests. The results also indicated that despite the low microbial loads that were categorized as trace, very low, or low on Xpert Ultra, yet, complete detection was achieved with some sample types (i.e., 100% detection). Consequently, Xpert Ultra has great potential to replace conventional diagnostic approaches as a standard detection method for EPTB.

Eflornithine Hydrochloride-Loaded Electrospun Nanofibers as a Potential Face Mask for Hirsutism Application.

Hirsutism is a distressing condition that can affect women's self-esteem due to the excessive amount of hair growth in different body parts, including the face. A temporary managing option is to develop a self-care routine to remove unwanted hair through shaving or waxing. Laser or electrolysis are alternative methods, but in some cases, the use of medications, such as the topical cream Vaniqa®, can help in reducing the growth of unwanted hair. Electrospun fibers have been used in several drug delivery applications, including skin care products, owing to their biocompatibility, biodegradability, high surface area-to-volume ratio, and dry nature that can release the encapsulated drugs with maximum skin penetration. Therefore, polyvinyl pyrrolidone (PVP) fibers were fabricated in combination with hyaluronic acid to deliver the active compound of Vaniqa®, i.e., Eflornithine hydrochloride (EFH), as a face mask to inhibit excess facial hair growth. The prepared drug-loaded fibers showed a diameter of 490 ± 140 nm, with an encapsulation efficiency of 88 ± 7% and a drug loading capacity of 92 ± 7 µg/mg. The in vitro drug release of EFH-loaded fibers exhibited an initial burst release of 80% in the first 5 min, followed by a complete release after 360 min, owing to the rapid disintegration of the fibrous mat (2 s). The in vitro cytotoxicity indicated a high safety profile of EFH at all tested concentrations (500-15.625 µg/mL) after 24-h exposure to human dermal fibroblast (HFF-1) cells. Therefore, this drug-loaded nanofibrous system can be considered a potentially medicated face mask for the management of hirsutism, along with the moisturizing effect that it possesses. Topical applications of the developed system showed reduced hair growth in mice to a certain extent.

Recent Advancement in mRNA Vaccine Development and Applications.

Messenger RNA (mRNA) vaccine development for preventive and therapeutic applications has evolved rapidly over the last decade. The mRVNA vaccine has proven therapeutic efficacy in various applications, including infectious disease, immunotherapy, genetic disorders, regenerative medicine, and cancer. Many mRNA vaccines have made it to clinical trials, and a couple have obtained FDA approval. This emerging therapeutic approach has several advantages over conventional methods: safety; efficacy; adaptability; bulk production; and cost-effectiveness. However, it is worth mentioning that the delivery to the target site and in vivo degradation and thermal stability are boundaries that can alter their efficacy and outcomes. In this review, we shed light on different types of mRNA vaccines, their mode of action, and the process to optimize their development and overcome their limitations. We also have explored various delivery systems focusing on the nanoparticle-mediated delivery of the mRNA vaccine. Generally, the delivery system plays a vital role in enhancing mRNA vaccine stability, biocompatibility, and homing to the desired cells and tissues. In addition to their function as a delivery vehicle, they serve as a compartment that shields and protects the mRNA molecules against physical, chemical, and biological activities that can alter their efficiency. Finally, we focused on the future considerations that should be attained for safer and more efficient mRNA application underlining the advantages and disadvantages of the current mRNA vaccines.

Current status and vision of local pharmaceutical industries in Saudi Arabia: The focus on nanomedicines.

Background: Pharmaceutical nanomedicine products are expected to impact the global pharmaceutical market and healthcare system significantly. Since 2000, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved over 80 nanomedicine products for marketing; an additional double that number is currently being tested in clinical trials. The nanomedicine market is expected to reach USD 350.8 billion by 2025 from USD 138.8 billion in 2016. This demonstrates the importance of nanotechnology to the delivery of pharmaceuticals. The main benefits of employing nanotechnology to distribute therapeutic agents include reducing the undesired toxicity from non-specific distribution and increasing patient adherence, which can indirectly minimize the burden on the country's healthcare system. Such products are expected to gain a significant economic impact on Saudi Arabia's pharmaceutical drugs market once they get developed locally. Method: A descriptive and cross-sectional study, including a web-based questionnaire and a complete categorization of pharmaceutical products formed by the national industries in Saudi Arabia, was utilized to investigate the current and future direction of pharmaceutical manufacturing exploiting nanotechnology in the Kingdom. Results: The survey showed an apparent lack of willingness within the national pharmaceutical industries, as the majority (≈ 86%) of the leading Saudi companies cannot enable nanotechnology-based medicines in their manufacturing. However, more than 93% of the national pharmaceutical industries, upon the basis of the responses, agreed that the development of pharmaceutical products with nanotechnology is an important step toward solving various complications associated with conventional forms of the available medicine. Conclusion: National pharmaceutical industries in Saudi Arabia will need to get closer to manufacturing nanomedicines by partnering with international pioneer companies. In addition, empowering the local research and development (R&D) centers in nano delivery systems could facilitate translating their R&D outcomes into novel advanced and commercialized products. This could imitate the direction of the global pharmaceutical market and share its revenue which will positively reflect on the Kingdom's economy.

GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

Development of Imeglimin Electrospun Nanofibers as a Potential Buccal Antidiabetic Therapeutic Approach.

The prevalence of type 2 diabetes (T2D) has been growing worldwide; hence, safe and effective antidiabetics are critically warranted. Recently, imeglimin, a novel tetrahydrotriazene compound, has been approved for use in T2D patients in Japan. It has shown promising glucose-lowering properties by improving pancreatic beta-cell function and peripheral insulin sensitivity. Nevertheless, it has several drawbacks, including suboptimal oral absorption and gastrointestinal (GI) discomfort. Therefore, this study aimed to fabricate a novel formulation of imeglimin loaded into electrospun nanofibers to be delivered through the buccal cavity to overcome the current GI-related adverse events and to provide a convenient route of administration. The fabricated nanofibers were characterized for diameter, drug-loading (DL), disintegration, and drug release profiles. The data demonstrated that the imeglimin nanofibers had a diameter of 361 ± 54 nm and DL of 23.5 ± 0.2 µg/mg of fibers. The X-ray diffraction (XRD) data confirmed the solid dispersion of imeglimin, favoring drug solubility, and release with improved bioavailability. The rate of drug-loaded nanofibers disintegration was recorded at 2 ± 1 s, indicating the rapid disintegration ability of this dosage form and its suitability for buccal delivery, with a complete drug release after 30 min. The findings of this study suggest that the developed imeglimin nanofibers have the potential to be given via the buccal route, thereby achieving optimal therapeutic outcomes and improving patient compliance.

Developing Wolbachia-based disease interventions for an extreme environment.

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced egg hatch under a range of environmental conditions, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.

Antimicrobial Resistance Awareness, Antibiotics Prescription Errors and Dispensing Patterns by Community Pharmacists in Saudi Arabia.

BACKGROUND: Antibiotic overuse and misuse have greatly facilitated the development of antimicrobial resistance (AMR). The Kingdom of Saudi Arabia is one of the countries that took a strategic approach, beginning with the prohibition of over-the-counter antibiotic dispensing, followed by the implementation of antimicrobial stewardship programs and various educational and awareness governmental activities and plans. However, the status of antibiotic prescriptions and dispensing in Saudi community pharmacies is still unclear. As a result, this study investigates community pharmacists' antibiotic dispensing practices and their knowledge of their role in fighting AMR, in addition to the status of antibiotic prescribing errors by physicians. METHOD: This is an online-based survey study of 671 participants distributed among community pharmacists of large pharmacy chains throughout the Saudi Arabia. RESULT: A number of 671 community pharmacists were participated in total, with a response rate of 96.57% (648 responses). The majority of community pharmacists (67%) had a long experience (>5 years) in this field. An antibiotic prescribing error was prevalent, with a mean of 3.32 per month in each pharmacy. Dentists (36.7%) and general practitioners (28.7%) were the most prescribers associated with antibiotic prescription errors. Most community pharmacists had a generally good practice of dispensing antibiotics, accounting for 71.5% of daily antibiotic dispensing. However, more than one-third of those pharmacists (35.2%) agreed on dispensing topical antibiotics without a prescription, based on their evaluation of the case presented in the pharmacy, as the majority of community pharmacists demonstrated a significant understanding of AMR. CONCLUSION: The current study demonstrated that there is a good antibiotic dispensing practice in the community pharmacies in Saudi Arabia, in addition to a substantial understanding of the community pharmacist's vital role in fighting AMR. This study could inform decision-makers on antibiotic usage in Saudi community pharmacies to improve the current inappropriate antibiotic use and dispensing situation and, thus, control AMR spread in Saudi Arabia.

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia.

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic 'Umrah' ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia.

Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities.

Neurodegenerative and neuronal-related diseases are major public health concerns. Human vulnerability to neurodegenerative diseases (NDDs) increases with age. Neuronal hormones and neurotransmitters are major determinant factors regulating brain structure and functions. The implications of environmental and climatic changes emerged recently as influence factors on numerous diseases. However, the complex interaction of neurotransmitters and neuronal hormones and their depletion under environmental and climatic influences on NDDs are not well established in the literature. In this review, we aim to explore the connection between the environmental and climatic factors to NDDs and to highlight the available and potential therapeutic interventions that could use to improve the quality of life and reduce susceptibility to NDDs.

Spatio-Temporal Modelling Informing Wolbachia Replacement Releases in a Low Rainfall Climate.

Releases of Aedes aegypti carrying Wolbachia bacteria are known to suppress arbovirus transmission and reduce the incidence of vector-borne diseases. In planning for Wolbachia releases in the arid environment of Jeddah, Saudi Arabia, we collected entomological data with ovitraps across a 7-month period in four locations. Herein, we show that mosquito presence in basements does not differ from that of non-basement areas of buildings. In modelling mosquito presence across the study sites, we found the spatial structure to be statistically significant in one of the four sites, while a significant spatial structure was found for egg production data across three of the four sites. The length scales of the spatial covariance functions fitted to the egg production data ranged from 143 m to 574 m, indicating that high productivity regions can be extensive in size. Rank-correlation analyses indicated that mosquito presence tended to persist from the dry to wet season, but that egg production ranks at locations could reverse. The data suggest that, in Jeddah, the quality of the local environment for breeding can vary over time. The data support the feasibility of dry season releases but with release numbers needing to be flexible depending on local rates of invasion.