Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation.

Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreased N -glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy. Highlights: The interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo.ER-localized GBP5 restricts N-linked glycosylation of SARS-CoV-2 spike protein, leading to protein misfolding and preventing transport to the Golgi apparatus.GBP5 binds to OST complex accessory proteins and potentially blocks access of the catalytic subunit to the spike protein.GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2Pharmacological inhibition of OST blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV. Significance: Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. We found that the interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo. GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2. Importantly, pharmacological inhibition of Oligosaccharyltransferase (OST) Complex blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV, indicating future translational application of our findings.

Burns During Covid-19 Pandemic: Demographics, Etiological and Clinical Trends in 2021 at the National Burn Care Centre in Islamabad, Pakistan.

The scarcity of data on burn-related injuries in Pakistan prompted this study. The study is specifically aimed at assessing the burn patients who were admitted to a national burn care center (BCC) in Pakistan. This single-center retrospective analysis was conducted for 12 months from January to December 2021. During this time period, 14,069 patients visited BCC with burn injuries of diverse natures while 613 of them were admitted. The patients' information was abstracted from the hospital database. This information included age, sex, diagnosis, burn depth/degree, time of arrival, circumstances of burn injury, TBSA (total burn surface area), complications, outcome, and management plan. This information was shifted to Microsoft Office Excel Worksheet 2015 and then coded into the IBM Statistical Package for the Social Sciences (SPSS) version 24.0. Armonk, NY: IBM Corp. Of 14,069 patients, 613 were admitted to the burn care center, indicating an admission rate of 4.35%. Among these 613 patients, there was a high proportion of males (58.89%) and a mean age of 20.2±12.5 years. Most patients (40.4%) visited within the first hour after being burnt and flame burns were the most common (41.10%). Most patients were burnt due to accidents (97.7%). The mean length of hospital stay was 15.5 days. Flames were the main cause of burns among our cohort of patients. Most patients had a TBSA of >10% and generally had a second-degree burn, mostly in the pediatric population. An urgent appraisal of burn policies and related legislation is needed to halt the burn burden in the country.

Cette étude a été décidée en raison de la pauvreté des données épidémiologiques concernant les brûlures au Pakistan. Il s'agit d'une étude monocentrique rétrospective sur dossier conduite dans le CTB national d'Islamabad sur l'année 2021. Sur les 14 069 patients brûlés qui s'y sont présentés, 613 (4,35%) ont été hospitalisés. Nous avons recueilli l'âge, le sexe, la SCB, la profondeur, la cause, le délai de présentation, la stratégie thérapeutique, les complications et le devenir des patients. Les données ont été implantée dans Excel et analysées avec SSPS 24.0. Parmi les patients hospitalisés, 58,89% étaient des hommes âgés de 20,2±12,5 ans. Le délai de présentation était de moins de 1h dans 40,4% des cas et l'atteinte était quasiment toujours accidentelle (97,7%), majoritairement par flamme (41%). La DMS était de 15,5 j. L'atteinte était le plus souvent > 10% SCT, habituellement au 2ème degré en particulier en population pédiatrique. Une évaluation de la législation préventive est urgente, afin de mettre fin au fardeau que représentent les brûlures dans notre pays.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Development and laboratory validation of a plant-derived repellent blend, effective against Aedes aegypti [Diptera: Culicidae], Anopheles gambiae [Diptera: Culicidae] and Culex quinquefasciatus [Diptera: Culicidae].

Mosquitoes of the genera Aedes, Anopheles and Culex vector a wide range of pathogens seriously affecting humans and livestock on a global scale. Over-reliance on insecticides and repellents has driven research into alternative, naturally-derived compounds to fulfil the same objectives. Steam distilled extracts of four plants with strong, yet attractive, volatile profiles were initially assessed for repellency in a dual-port olfactometer using Aedes aegypti as the model species. Picea sitchensis was found to be the most repellent, proving comparable to leading products when applied at 100% (p = 1.000). Key components of conifer-derived volatile profiles were then screened via electroantennography before those components eliciting an electrophysiological response were assayed individually in the olfactometer; according to WHO protocol. The most promising 5 were selected for reductive analyses to produce an optimised semiochemical blend. This combination, and a further two variations of the blend, were then progressed to a multi-species analysis using the BG-test whereby bite-attempt frequency on hands was assessed under different repellent treatments; assays were compared between Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus. Efficacy was found against all three species, although it was found that Ae. aegypti was the most susceptible to the repellent, with An. gambiae being the least. Here, a novel, naturally-derived blend is presented with weak spatial repellency, as confirmed in laboratory assays. Further work will be required to assess the full extent of the potential of the products, both in terms of field application and species screening; however, the success of the products developed demonstrate that plant metabolites have great capacity for use in the repellent sector; both to improve upon known compounds and to reduce the usage of toxic products currently on the market.

Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence.

Significance: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. Approach: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). Results: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. Conclusions: We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.

Assessment of Babesia spp. prevalence in various domestic animals across Southern Punjab, Pakistan.

Parasitic diseases, notably babesiosis, exert a substantial impact on the global cattle industry, posing challenges to commerce, economies, and human health. This study, conducted in Southern Punjab, Pakistan, aimed to assess the prevalence of Babesia spp. across various livestock species using microscopic and PCR methods. A total of 180 blood samples (60 from each district) were systematically collected from apparently healthy animals, with 36 samples obtained from each domestic animal species, including camel, cattle, buffalo, goat, and sheep, noting that 12 samples were collected from each district for each animal species. Overall prevalence was determined to be 32.8% (59/180), with varying rates among species: 25.0% in cattle, 41.66% in buffalo, 30.55% in goats, 33.3% in sheep, and 33.3% in camels. Microscopic examination revealed slightly varied infection rates among large and small domestic animals (22.2%), while PCR results indicated a 32.8% overall infection rate in both large and small domestic animals, with no statistical significance. District-wise analysis showed regional variations, with Muzaffargarh recording a prevalence rate of 23.33% through microscopic examination, while Lodhran and Bahawalpur recorded 21.67%. PCR results revealed higher rates (38.33%, 26.67%, and 33.33%, respectively), underlining the importance of employing PCR for accurate detection. Examining ruminant types, large ruminants exhibited a 32.4% infection rate, while small domestic animals showed 33.3%, with no significant difference (p=0.897). District-wise prevalence showcased significant variation, with Muzaffargarh demonstrating a 25% prevalence, Lodhran 22%, and Bahawalpur 22%, through microscopic examination. PCR results displayed 38.33%, 27%, and 33.3%, respectively, with no statistical significance. Detailed analysis of individual districts highlighted variations in infection rates among camels, cattle, buffalo, goats, and sheep. The binomial test indicated significant differences through microscopic analysis (P=0.011) but non-significant variations through PCR (P=0.065), emphasizing the precision of PCR. Regional variations in prevalence, notably with Punjab exhibiting the highest frequency (33.87%) and KPK the lowest (13.24%), suggest potential influences from varying veterinary practices and environmental factors. This study underscores the pivotal role of PCR alongside microscopy for accurate babesiosis diagnosis. These findings contribute to the broader understanding of babesiosis prevalence, emphasizing the necessity of advanced molecular techniques for informed control measures.

Unlocking the Potential of Cellular Guidance in Endodontics: Advancing the Process of Pulp Regeneration and Beyond.

Regenerative endodontics represents a paradigm shift in dental therapy, with the potential to not only restore damaged dental tissues but also to preserve the vitality of teeth. At the heart of this innovative approach is cell homing, a technique that harnesses the body's own healing mechanisms by recruiting endogenous stem cells to the site of dental injury for effective tissue regeneration. This review delves into the intricate processes of cell homing in the context of regenerative endodontics, particularly focusing on its application in immature teeth with open apices. It examines the role of bioactive molecules, scaffolds, and growth factors in orchestrating cell migration and differentiation within the root canal space. In addition, the review addresses the current limitations in clinical practice, such as the challenges in completely regenerating the pulp-dentin complex and the unpredictability in long-term outcomes. It also explores future possibilities, including the potential for more refined and effective regenerative strategies. By providing a comprehensive overview of the current state of cell homing in regenerative endodontics, this article aims to contribute to the ongoing development of advanced therapeutic techniques that could revolutionize endodontic treatment and improve patient care.

Identification of the odorant binding proteins of Western Flower Thrips (Frankliniella occidentalis), characterization and binding analysis of FoccOBP3 with molecular modelling, molecular dynamics simulations and a confirmatory field trial.

Olfactory systems are indispensable for insects as they, including Western Flower Thrips (Frankliniella occidentalis), use olfactory cues for ovipositing and feeding. F. occidentalis use odorant binding proteins (OBPs) to transport semiochemicals to odorant receptors to induce a behavioural response from the sensillum lymph of the insect's antennae. This study identifies four OBPs of F. occidentalis and analyses their expression at three stages of growth: larvae, adult males and adult females. Further, it investigates the presence of conserved motifs and their phylogenetic relationship to other insect species. Moreover, FoccOBP3 was in silico characterized to analyse its structure along with molecular docking and molecular dynamics simulations to understand its binding with semiochemicals of F. occidentalis. Molecular docking revealed the interactions of methyl isonicotinate, p-anisaldehyde and (S)-(-)-verbenone with FoccOBP3. Moreover, molecular dynamics simulations showed bonding stability of these ligands with FoccOBP3, and field trials validated that Lurem TR (commercial product) and p-anisaldehyde had greater attraction as compared to (S)-(-)-verbenone, given the compound's binding with FoccOBP3. The current study helps in understanding the tertiary structure and interaction of FoccOBP3 with lures using computational and field data and will help in the identification of novel lures of insects in the future, given the importance of binding with OBPs.Communicated by Ramaswamy H. Sarma.

Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Redox regulation of m6A methyltransferase METTL3 in ß-cells controls the innate immune response in type 1 diabetes.

Type 1 diabetes (T1D) is characterized by the destruction of pancreatic ß-cells. Several observations have renewed the interest in ß-cell RNA sensors and editors. Here, we report that N6-methyladenosine (m6A) is an adaptive ß-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m6A writer methyltransferase 3 (METTL3) levels increase drastically in ß-cells at T1D onset but rapidly decline with disease progression. m6A sequencing revealed the m6A hypermethylation of several key innate immune mediators, including OAS1, OAS2, OAS3 and ADAR1 in human islets and EndoC-ßH1 cells at T1D onset. METTL3 silencing enhanced 2'-5'-oligoadenylate synthetase levels by increasing its mRNA stability. Consistently, in vivo gene therapy to prolong Mettl3 overexpression specifically in ß-cells delayed diabetes progression in the non-obese diabetic mouse model of T1D. Mechanistically, the accumulation of reactive oxygen species blocked upregulation of METTL3 in response to cytokines, while physiological levels of nitric oxide enhanced METTL3 levels and activity. Furthermore, we report that the cysteines in position C276 and C326 in the zinc finger domains of the METTL3 protein are sensitive to S-nitrosylation and are important to the METTL3-mediated regulation of oligoadenylate synthase mRNA stability in human ß-cells. Collectively, we report that m6A regulates the innate immune response at the ß-cell level during the onset of T1D in humans.

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone.

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L., known as "Abhal" in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-ß) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR-induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-ß and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke.

Knowledge, Attitude, and Practices Related to Foot Care Among Diabetic Patients in Tabuk City, Saudi Arabia.

Introduction Diabetic foot ulcer (DFU) is a prevalent complication of diabetes mellitus (DM), affecting approximately 15% of all diabetic patients. This condition poses significant challenges due to its association with major morbidity, mortality, high costs, and diminished quality of life. The incidence of diabetic foot complications among diagnosed diabetes cases is alarming, making it a primary concern in diabetes management. Diabetes mellitus, a chronic metabolic disorder, impacts nearly every system in the body. Methods In this study, a cross-sectional design was employed to assess the level of knowledge, attitude, and practices related to foot care among 432 diabetic patients in Tabuk City, Saudi Arabia. Results The participants' ages ranged from 18 to above 60 years, with (n = 206, 47.69%) being male and (n = 226, 52.31%) female. Type 2 diabetes was prevalent, constituting (n = 277, 64.12%) of cases, whereas (n = 187, 38.29%) had type 1 diabetes. Approximately (n= 224, 51.9%) of patients had been diagnosed with diabetes for less than 10 years. A significant portion (n= 302, 69.91%) of patients did not report any foot complaints. However, (n= 88, 20.37%) had a history of healed ulcers, and (n= 21, 4.9%) had undergone amputation due to diabetes. The majority of patients (n = 228, 52.78%) were under oral agent treatment. Conclusion The study population demonstrated adequate knowledge about diabetes management and exhibited positive attitudes toward diabetes and its related complications, particularly concerning foot care. While most patients displayed appropriate practices related to diabetic foot care, some participants showed inadequate adherence to essential procedures. Addressing these gaps in knowledge and practices is crucial for enhancing the overall management of diabetic foot complications among patients.

Hybrid Radiant Disinfection: Exploring UVC and UVB Sterilization Impact on the Mechanical Characteristics of PLA Materials.

This study explores the impact of disinfection techniques on the mechanical properties of poly(lactic acid) (PLA), a crucial material in the production of medical implants, tissue engineering, orthopedic devices and drug delivery systems, owing to its biocompatibility and ease of manufacturing. The focus is on evaluating the effectiveness of ultraviolet (UV) type C (254 nm wavelength) and the combined use of type C and B (310 nm wavelength) disinfection methods. Fifteen tensile test specimens (ASTM D638) and fifteen compression test specimens (ASTM D695) were utilized to assess PLA's mechanical properties, including yield strength, ultimate strength, and fracture strength. The investigation involved subjecting the specimens to the specified disinfection methods and evaluating these properties both before and after the disinfection process. In the tensile test, a statistically significant difference (p = 0) in yield displacement was observed among the three groups. Additionally, a notable difference (p = 0.047) in fracture displacement was identified between the untreated group and the UVC and UVB combination group. No discernible impact on yield or fracture forces was noted. In the compression test, there was a significant difference (p = 0.04) in yield displacement and a clear difference (p = 0.05) in fracture force between the untreated group and the UVC and UVB combination group. The hybrid combination of UVC and UVB disinfection techniques did not affect yield force in both tensile and compression tests. However, it demonstrated a clear impact on displacement, suggesting its potential as a promising disinfection technique in the medical field.

Epidemiology, Causes, and Management of Gastro-esophageal Reflux Disease: A Systematic Review.

Our comprehensive systematic review aimed to examine gastroesophageal reflux disease (GERD), a disorder that occurs when stomach contents flow back into the esophagus. It may manifest as either non-erosive reflux disease or erosive esophagitis. The activity depicts the assessment and medical management of GERD and emphasizes the interprofessional team's involvement to enhance care for people with this ailment. Data sources were PubMed/Medline and Embase. Our review investigated English-language articles (from 2014 to 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall, there were seven articles. Surveys and analyses of national databases were the most widely used methods (n=7). The search identified 3,730 studies, and seven were eligible for inclusion in the analysis. Further understanding of GERD and treatment protocols may help improve evaluation and management in the future. Millions of individuals worldwide suffer from GERD, a common clinical condition. Patients can be identified by symptoms that are both common and uncommon. For many GERD patients, acid suppression treatment reduces symptoms and avoids clinical complications. Our capacity to recognize and treat disease consequences has improved with the advancement of diagnostic and treatment methods. Here, we go into the etiology and consequences of GERD and offer details on the treatment strategy for this prevalent illness.

Pseudoaneurysm and Renal Artery Stenosis Post-renal Transplant: A Rare Presentation.

We report the case of a 51-year-old gentleman who underwent living renal transplantation in Pakistan for end-stage renal disease one and a half years ago. He presented to our hospital with renal artery stenosis and an extra-renal pseudoaneurysm at the anastomotic site of the transplanted kidney. This can cause graft dysfunction and hypertension due to impairment of arterial perfusion in the transplanted kidney. Treatment with percutaneous transluminal angioplasty and covered stenting of the pseudoaneurysm and stenosis improved kidney function and hypertension.

LDMRes-Net: A Lightweight Neural Network for Efficient Medical Image Segmentation on IoT and Edge Devices.

In this study, we propose LDMRes-Net, a lightweight dual-multiscale residual block-based convolutional neural network tailored for medical image segmentation on IoT and edge platforms. Conventional U-Net-based models face challenges in meeting the speed and efficiency demands of real-time clinical applications, such as disease monitoring, radiation therapy, and image-guided surgery. In this study, we present the Lightweight Dual Multiscale Residual Block-based Convolutional Neural Network (LDMRes-Net), which is specifically designed to overcome these difficulties. LDMRes-Net overcomes these limitations with its remarkably low number of learnable parameters (0.072M), making it highly suitable for resource-constrained devices. The model's key innovation lies in its dual multiscale residual block architecture, which enables the extraction of refined features on multiple scales, enhancing overall segmentation performance. To further optimize efficiency, the number of filters is carefully selected to prevent overlap, reduce training time, and improve computational efficiency. The study includes comprehensive evaluations, focusing on the segmentation of the retinal image of vessels and hard exudates crucial for the diagnosis and treatment of ophthalmology. The results demonstrate the robustness, generalizability, and high segmentation accuracy of LDMRes-Net, positioning it as an efficient tool for accurate and rapid medical image segmentation in diverse clinical applications, particularly on IoT and edge platforms. Such advances hold significant promise for improving healthcare outcomes and enabling real-time medical image analysis in resource-limited settings.

Knowledge and Awareness of Screening for Prostate Cancer Risk Factors and Symptoms Among the General Population in Tabuk City, Saudi Arabia.

Background Early-stage prostate cancer may not show any signs. Digital rectal examination and the prostate-specific antigen test are frequently used in the screening for prostate cancer. The objective of this research is to assess the knowledge and awareness of screening prostate cancer among males in Tabuk, Saudi Arabia. Methodology A cross-sectional study was performed among Saudi males in Tabuk City. A structured interviewing technique based on a questionnaire was used based on the objectives and research questions. Data were collected by well-trained data collectors from the general population in Tabuk City who were randomly chosen in proportion to the city's population density. A multivariate logistic regression analysis was done to evaluate the variables related to knowledge and awareness in this study. Results This questionnaire was completed by a total of 417 male participants. In the studied group, 86.8% of participants had heard about prostate cancer through friends (59%), TV/radio/newspaper (53.24%), and other health services (41.49%). In addition, around 67.6% of participants knew about the prostate cancer screening test. In addition, 32.4% of participants had no prior knowledge of prostate cancer or a screening test. Conclusions There was a good level of awareness and attitude toward screening methods for prostate cancer (54.7%). Aside from having good knowledge regarding prostate cancer symptoms among males in Tabuk City, all participants with regard to demographic distribution showed a significant level of good knowledge and awareness of screening prostate cancer methods and the necessity of performing regular prostate examinations.

Measurement of Occupational Eye and Thyroid Radiation Doses in Pediatric Interventional Cardiologists at a Tertiary Hospital.

Background Advances in imaging techniques have led to increased utilization of imaging devices in catheterization laboratories. Invasive surgical procedures for cardiac disorders have been largely replaced by fluoroscopic cardiac catheterization. With this increase, concerns and risks associated with exposure to ionizing radiation among interventional cardiologists are growing. This study aims to measure and compare the occupational doses to the eye lens and thyroid of pediatric interventional cardiologists during different procedures in the catheterization laboratory and its significance. Methodology In this study, cardiologists wore bandanas with attached dosimeters to measure the absorbed doses to the eyes and thyroid gland. The dosimeters were collected for reading. The procedure types were also collected. In addition, the total fluoroscopy time and tube voltage of the biplane machine were measured. SPSS version 23 (IBM Corp., Armonk, NY, USA) was used to analyze the data. The characteristics of the study sample were described using simple counts and percentages, whereas means and standard deviations were used for continuous variables. Statistical significance was set at p-values <0.05. Results A total of 93 procedures were evaluated. The mean absorbed doses for all 93 procedures in both eyes and thyroid were 0.09 mGy and 0.08 mGy, respectively. A significant difference was found between the left and right eye measurements (p = 0.034), with higher doses administered to the left eye. However, no significant difference was observed between the right and left thyroid doses (p = 0.281). Significant correlations were found between the eye and thyroid doses and the procedure type (p = 0.02 and p = 0.009, respectively). Conclusions A significant amount of radiation was measured in the measurements of both organs. In addition, radiation dose measurements varied between different types of procedures. Our current results indicate the importance and necessity of applying the radiation protection concept of dose optimization.

Quantification of Suvorexant in Human Urine Using a Validated HPTLC Bioanalytical Method.

Suvorexant (SUV) is a new sedative/hypnotic medicine that is recommended to treat insomnia. It is an important medicine from a forensic point of view due to its sedative/hypnotic and depressant effects. To the best of our knowledge, high-performance thin-layer chromatography (HPTLC) bioanalytical methods have not been published to measure SUV in human urine and pharmaceutical samples. Accordingly, this study was designed and validated a sensitive and rapid bioanalytical HPTLC method to determine SUV in human urine samples for the very first time. The densitometric measurement of SUV and the internal standard (IS; sildenafil) was performed on glass-coated silica gel normal-phase-60F254S TLC plates using a mixture of chloroform and methanol (97.5:2.5 v/v) as the eluent system. Both the SUV and IS were detected at a wavelength of 254 nm. Both analytes were extracted using the protein precipitation technique utilizing methanol as the solvent. For the IS and SUV, the Rf values were 0.09 and 0.45, respectively. The proposed bioanalytical method for SUV was linear in the 50-1600 ng/band range. The current bioanalytical technique was linear, precise (% RSD = 3.28-4.20), accurate (% recovery = 97.58-103.80), robust (% recovery = 95.31-102.34 and % RSD = 2.81-3.15), rapid, and sensitive (LOD = 3.73 ng/band and LOQ = 11.20 ng/band). These findings suggested that the current bioanalytical method can be regularly used to determine SUV in wide varieties of urine samples.

Generation of 3D lung organoids from human induced pluripotent stem cells for modeling of lung development and viral infection.

The lack of physiologically relevant in vitro models has hampered progress in understanding human lung development and disease. Here, we describe a protocol in which human induced pluripotent stem cells (hiPSCs) undergo stepwise differentiation into definitive endoderm (>88% population) to three-dimensional (3D) lung organoids (LORGs), which contain both epithelial and mesenchymal cellular architecture and display proximal and distal airway patterning. These LORGs can maintained for more than 90 days by re-embedding in the Matrigel. We show the utility of LORGs for disease modeling and drug screening by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treatment with antiviral drugs.