Consanguineous marriages, premarital screening, and genetic testing: a survey among Saudi university students.

Background: Marriage among cousins or close relatives, i.e., consanguinity, is prevalent in many parts of the world, especially the Muslim world. Across civilizations, cultural norms, religious beliefs, and economic factors affect consanguineous marriages (CMs); however, such marriages have social, genetic, and health repercussions. The present study investigated the university students' attitudes regarding CMs and factors influencing their attitudes at King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia (KSA). Methods: This cross-sectional prospective study was conducted at KAU Jeddah in 2023. The questionnaire was distributed via electronic media (Emails, Facebook Messenger & WhatsApp). The convenience sampling technique was used to select participants, and descriptive and inferential statistics were used to analyze the data on SPSS-26. Results: A total of 1707 university students were part of the study (females, 1,198, 70.2%; males, 509, 29.8%). Almost half of the participants, 819 (48.0%), had parents with CMs. Most of the participants, 1,391 (81.5%), had CMs in the family. Half of the participants disagreed that parents consider marriage stable due to high compatibility and the same social relationship before and after marriage. About one-third of respondents said parents believe family marriage transmits cultural values and continuity and keeps wealth in the family. More than three-fourths of the participants stated that if marriage is arranged with first cousins, they will opt for genetic analysis (82.5%) and premarital counseling (85.2%). The personal attitudes of females (p < 0.001), undergraduate (p = 0.02), and health sciences students (p = 0.02) were more positive than their counterparts. Males (OR = 0.41; p < 0.001) and non-health sciences students (OR = 0.68; p = 0.01) were less likely to have significant positive attitudes than their counterparts. Among participants who had CM parents, males (OR = 0.397; p < 0.001) and non-health sciences students (OR = 0.60; p = 0.01) and urban residents (OR = 0.59; p = 0.01) had significantly lower odds of having a positive attitude than their counterparts. Conclusion: The practice of CMs is still prevalent in Saudi culture, with almost half of the participants having CM parents and the majority reporting these marriages in their families. Personal attitudes toward CMs were extremely positive. Most students prefer genetic testing and premarital counseling if marrying first cousins. Gender, faculty, parental income, and educational background influenced participants' attitudes.

Fabrication and optimization of febuxostat-loaded chitosan nanocarriers for better pharmacokinetics profile.

The current research was planned to enhance the bioavailability of hydrophobic drug after oral administration through the development of a nanoparticle drug delivery system (DDS). Therefore, febuxostat-loaded chitosan nanoparticles (FLC NPs) were prepared using a modified ionic gelation method and optimized the reaction conditions through the design of experiments. Design expert software was used to check the desirability of the central composite design and the interactive effects of the independent variables (chitosan concentration, ratio of chitosan to linker, and pH of the medium) on the response variables (size distribution, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE)) of FLC NPs. All ingredients of the optimized formulation (formulation Q) were compatible with each other as evident from FTIR, PXRD, and TGA studies, and displayed 234.7 nm particle size, 0.158 PDI, 25.8 mV zeta potential, and 76.9 % EE. TEM, SEM, and AFM exhibited a smooth, dense, and uniform structure without any visible pores in the structure of FLC NPs. The in vitro and in vivo drug release studies described a sustained release pattern of febuxostat and increased relative bioavailability by 286.63 %. Considering these findings, this chitosan nanoparticle DDS can further be used for improving the EE and bioavailability of hydrophobic drugs.

Nanotechnology-based radiation therapy to cure cancer and the challenges in its clinical applications.

Radiation therapy against cancer frequently fails to attain the desired outcomes because of several restricting aspects. Radiation therapy is not a targeted antitumor treatment, and it poses serious threats to normal tissues as well. In many cases, some inherent features of tumors make them resistant to radiation therapy. Several nanoparticles have shown the capacity to upgrade the viability of radiation treatment because they can directly interact with ionizing radiation to increase cellular radiation sensitivity. Several types of nanomaterials have been investigated as radio-sensitizers, to improve the efficacy of radiotherapy and overcome radio-resistance including, metal-based nanoparticles, quantum dots, silica-based nanoparticles, polymeric nanoparticles, etc. Despite all this research and development, certain challenges associated with the exploitation of nanoparticles to enhance and improve radiation therapy for cancer treatment are encountered. Potential applications of nanoparticles as radiosensitizers is hindered by the difficulties associated with ensuring their production at a large scale with improved characterizations and because of certain biological challenges. By overcoming the shortcomings of nanoparticles like working on the pharmacokinetics, and physical and chemical characterization, the therapy can be improved. It is expected that in the future more knowledge will be available regarding nanoparticles and their clinical efficacy, leading to the successful development of nanotechnology-based radiation therapies for a variety of cancers. This review highlights the limitations of conventional radiotherapy in cancer treatment and explores the potential of nanotechnology, specifically the use of nanomaterials, to overcome these challenges. It discusses the concept of using nanomaterials to enhance the effectiveness of radiation therapy and provides an overview of different types of nanomaterials and their beneficial properties. The review emphasizes the need to address the obstacles and limitations associated with the application of nanotechnology in cancer radiation therapy for successful clinical translation.

Leveraging health information helpline to sustain health-care delivery during the COVID pandemic: Experiences from a State in Eastern India.

Background: The unprecedented demands on health-care systems due to the COVID-19 pandemic made countries including India to switch toward alternative modes of health-care delivery. Objectives: The aim of this study was to describe the various COVID-related services delivered through 104 health information helpline (HIHL), located in Jharkhand during the pandemic. Methods: The de-identified secondary data from February 2020 to December 2021 related to COVID services delivered through HIHL were analyzed. Results: There was a significant increase in the COVID call volume during the first as well as the second wave. The HIHL has been able to guide the callers on testing, home isolation and follow-up, home-based teleconsultation, vaccination, timely referral, and support with logistic-related information. Conclusion: The 104 HIHL has played a critical role in sustaining health-care delivery during the pandemic, combating the "infodemic" and guiding the general public by providing authentic information.

A comprehensive review on traditional uses, phytochemistry and pharmacological properties of Paeonia emodi Wall. ex Royle: current landscape and future perspectives.

Paeonia emodi Wall. ex Royle is commonly known as Himalayan paeony has great importance as a food and medicine. The practice of Paeonia emodi Wall. ex Royle is very ancient and it is conventionally used for a wide range of illnesses in the folk system of medicine because of its wide beneficial phytochemical profile. The main purpose of the current review was the synthesis of recent data on botany, ethnopharmacology, phytochemistry and potential pharmacological mechanisms of action of Paeonia emodi Wall. ex Royle, thus offering new prospects for the development of new adjuvant natural therapies. Using scientific databases such as PubMed/MedLine, Scopus, Web of Science, ScienceDirect, Google Scholar, Springer, and Wiley, a comprehensive literature search was performed for Paeonia emodi Wall. ex Royle. For searching, we used the next MeSH terms: "Biological Product/isolation and purification", "Biological Products/pharmacology", "Drug Discovery/methods", "Ethnopharmacology, Medicine", "Traditional/methods", "Paeonia/chemistry", "Plant Extracts/pharmacology", "Phytochemicals/chemistry", "Phytochemicals/pharmacology", "Plants, Medicinal". The results of the most recent studies were analyzed and the most important data were summarized in tables and figures. Phytochemical research of Paeonia emodi Wall. ex Royle has led to the isolation of triterpenes, monoterpenes, phenolic acids, fatty acids, organic compounds, steroids, free radicals and some other classes of primary metabolites. In addition, diverse pharmacological activities like antibacterial, antifungal, anticoagulant, airway relaxant lipoxygenase and beta-glucuronidase inhibiting activity, radical scavenging activity, phytotoxic and insecticidal activities have been reported for Paeonia emodi Wall. ex Royle. Different bioactive compounds of Paeonia emodi Wall. ex Royle has proven their therapeutic potential in modern pharmacological and biomedical research to cure numerous gastrointestinal and nervous disorders. In future, further in vitro and in vivo therapeutic studies are required to identify new mechanisms of action, pharmacokinetics studies, and new pharmaceutical formulations for target transport and possible interaction with allopathic drugs. Also, new research regarding quality evaluation, toxicity and safety data in humans is needed.

Heparin-Loaded Alginate Hydrogels: Characterization and Molecular Mechanisms of Their Angiogenic and Anti-Microbial Potential.

Background: Chronic wounds continue to be a global concern that demands substantial resources from the healthcare system. The process of cutaneous wound healing is complex, involving inflammation, blood clotting, angiogenesis, migration and remodeling. In the present study, commercially available alginate wound dressings were loaded with heparin. The purpose of the study was to enhance the angiogenic potential of alginate wound dressings and analyze the antibacterial activity, biocompatibility and other relevant properties. We also aimed to conduct some molecular and gene expression studies to elaborate on the mechanisms through which heparin induces angiogenesis. Methods: The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Swelling ability was measured by soaking hydrogels in the Phosphate buffer at 37 °C, and cell studies were conducted to evaluate the cytotoxicity and biocompatibility of hydrogels in NIH3T3 (fibroblasts). Real-time PCR was conducted to check the molecular mechanisms of heparin/alginate-induced angiogenesis. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Results: FTIR confirmed the formation of heparin-loaded alginate wound dressing and the compatibility of both heparin and alginate. Among all, 10 µg/mL concentration of heparin showed the best antibacterial activity against E. coli. The swelling was considerably increased up to 1500% within 1 h. Alamar Blue assay revealed no cytotoxic effect on NIH3T3. Heparin showed good anti-microbial properties and inhibited the growth of E. coli in zones with a diameter of 18 mm. The expression analysis suggested that heparin probably exerts its pro-angiogenetic effect through VEGF and cPGE. Conclusions: We report that heparin-loaded alginate dressings are not cytotoxic and offer increased angiogenic and anti-bacterial potential. The angiogenesis is apparently taken through the VEGF pathway.

Antimicrobial activities of different solvent extracts from stem and seeds of Peganum Harmala L.

Wild medicinal herbs have been used as folk and traditional medicines all across the world since well before recorded history. This present study was designed to test the antimicrobial activities of five different solvent extracted samples (n-hexane, n-butanol, ethyl acetate, methanol, and water) of Peganum harmala using stems and seeds. Two different strains of Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacteria (Bacillus subtilus and Staphylococcus aureus), and one fungal strain (Candida albicans) were used. The antimicrobial activities were measured using a disc diffusion assay. Two concentrations of the extracts (1 and 2mgDisc-1) were used. Ethyl acetate fraction was found more affective among the tested solvents and showed maximum activity (zone of inhibition) against S. aureus (65.53 and 81.10%), E. coli (46.22 and 61.29%) while n-butanol and water fractions gave maximum activity against S. aureus (78.86 and 70.00%) and K. pneumonia (57.00 and 61.39%) respectively. Water fraction showed maximum activity against C. albicans (60.00 and 81.88%). In the case of the stem, Ethyl acetate again showed more activity against B. subtilus (38.57 and 42.10%) and S. aureus (36.66 and 46.66%) while n-butanol showed maximum activity against K. pneumonia (24.55 and 32.44%) and E. coli (27.93 and 37.61%). Methanol was found more effective against C. albicans (25.71 and 43.80%). Seed extracted samples were found more effective compared to the stem. Ethyl acetate, butanol, and aqueous extracted samples showed good activity against the tested microbes, so these fractions are recommended for study their mechanism of actions and isolation of bioactive metabolites responsible for antimicrobial activities. The P. harmala should be evaluated for their bioactive compounds to be used in future studies. Our objective is to provide the framework for future study on the roles of P. harmala as traditional medicines.

Bacteriophages fEV-1 and fD1 Infect Yersinia pestis.

Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.

Therapeutic effects of chitosan-embedded vitamin C, E nanoparticles against cisplatin-induced gametogenic and androgenic toxicity in adult male rats.

Cisplatin, an anticancer drug used in treating various types of cancers, can cause reproductive toxicities during chemotherapy. Keeping this in view, the present study was designed to investigate the possible protective effects of normal vitamin C and E and vitamin C and E nanoparticles (embedded in chitosan) against cisplatin-induced reproductive toxicities. Vitamins C, E, and their nanoparticles in this regard proved to be an effective therapy. The work aimed to treat cisplatin-induced reproductive toxicities through vitamin C and E and their nanoparticles. Cisplatin exposure caused significant reduction in the weight, testosterone level, and changed lipid profile. Similarly, cisplatin induced significant widespread testicular atrophy and testicular lesions as evidenced by the gaps in the epithelium and loss of differentiating germ cells. Vitamin C and E and their nanoparticles rescued the weight, testosterone level, and testicular disturbances, which is associated with improved histological view of testicular tissues. The current study highlights evidence that designing a medication of vitamin C and E nanoparticles is useful in mitigating cisplatin-induced reproductive toxicity in cancerous male patients underlying chemotherapy.

Knowledge of acute kidney injury among Pakistani nurses: A cross-sectional survey.

Nurses are increasingly being regarded as the nucleus of the health care system, as well as serving as an advocate for health-care consumers. Therefore, adequate acute kidney injury (AKI) knowledge of nurses would definitely have a positive impact on an early diagnosis, management, and outcome of AKI. This cross-sectional study was aimed to assess the knowledge of AKI among nurses working at public and private hospitals at Lahore and Sialkot, Pakistan. The study was conducted from October 2017 to March 2018. A convenient sampling method was used and data were gathered using a self-administered questionnaire. The median knowledge score of the study population (n = 200) was 29, with majority (78.5%) having moderate knowledge (score 26-38). Only 2.5% of nurses had good AKI knowledge whereas 19.0% were found to have poor knowledge. Nurses' age, rank, and their departments had no significant impact on the knowledge scores. Furthermore, there was no significant difference of knowledge among participants who had previously attended any seminar/special training session regarding AKI and those who had not. In conclusion, majority of Pakistani nurses had moderate AKI knowledge. Therefore, in-service training sessions on AKI should be conducted to equip nurses with up-to-date AKI knowledge.

The Podovirus ϕ80-18 Targets the Pathogenic American Biotype 1B Strains of Yersinia enterocolitica.

We report here the complete genome sequence and characterization of Yersinia bacteriophage vB_YenP_ϕ80-18. ϕ80-18 was isolated in 1991 using a Y. enterocolitica serotype O:8 strain 8081 as a host from a sewage sample in Turku, Finland, and based on its morphological and genomic features is classified as a podovirus. The genome is 42 kb in size and has 325 bp direct terminal repeats characteristic for podoviruses. The genome contains 57 predicted genes, all encoded in the forward strand, of which 29 showed no similarity to any known genes. Phage particle proteome analysis identified altogether 24 phage particle-associated proteins (PPAPs) including those identified as structural proteins such as major capsid, scaffolding and tail component proteins. In addition, also the DNA helicase, DNA ligase, DNA polymerase, 5'-exonuclease, and the lytic glycosylase proteins were identified as PPAPs, suggesting that they might be injected together with the phage genome into the host cell to facilitate the take-over of the host metabolism. The phage-encoded RNA-polymerase and DNA-primase were not among the PPAPs. Promoter search predicted the presence of four phage and eleven host RNA polymerase -specific promoters in the genome, suggesting that early transcription of the phage is host RNA-polymerase dependent and that the phage RNA polymerase takes over later. The phage tolerates pH values between 2 and 12, and is stable at 50°C but is inactivated at 60°C. It grows slowly with a 50 min latent period and has apparently a low burst size. Electron microscopy revealed that the phage has a head diameter of about 60 nm, and a short tail of 20 nm. Whole-genome phylogenetic analysis confirmed that ϕ80-18 belongs to the Autographivirinae subfamily of the Podoviridae family, that it is 93.2% identical to Yersinia phage fHe-Yen3-01. Host range analysis showed that ϕ80-18 can infect in addition to Y. enterocolitica serotype O:8 strains also strains of serotypes O:4, O:4,32, O:20 and O:21, the latter ones representing similar to Y. enterocolitica serotype O:8, the American pathogenic biotype 1B strains. In conclusion, the phage ϕ80-18 is a promising candidate for the biocontrol of the American biotype 1B Y. enterocolitica.

Curcumin as an Alternative Epigenetic Modulator: Mechanism of Action and Potential Effects.

Curcumin (a polyphenolic compound in turmeric) is famous for its potent anti-inflammatory, anti-oxidant, and anti-cancer properties, and has a great potential to act as an epigenetic modulator. The epigenetic regulatory roles of curcumin include the inhibition of DNA methyltransferases (DNMTs), regulation of histone modifications via the regulation of histone acetyltransferases (HATs) and histone deacetylases (HDACs), regulation of microRNAs (miRNA), action as a DNA binding agent and interaction with transcription factors. These mechanisms are interconnected and play a vital role in tumor progression. The recent research has demonstrated the role of epigenetic inactivation of pivotal genes that regulate human pathologies such as cancers. Epigenetics helps to understand the mechanism of chemoprevention of cancer through different therapeutic agents. In this regard, dietary phytochemicals, such as curcumin, have emerged as a potential source to reverse epigenetic modifications and efficiently regulate the expression of genes and molecular targets that are involved in the promotion of tumorigenesis. The curcumin may also act as an epigenetic regulator in neurological disorders, inflammation, and diabetes. Moreover, curcumin can induce the modifications of histones (acetylation/deacetylation), which are among the most important epigenetic changes responsible for altered expression of genes leading to modulating the risks of cancers. Curcumin is an effective medicinal agent, as it regulates several important molecular signaling pathways that modulate survival, govern anti-oxidative properties like nuclear factor E2-related factor 2 (Nrf2) and inflammation pathways, e.g., nuclear factor kappa B (NF-κB). Curcumin is a potent proteasome inhibitor that increases p-53 level and induces apoptosis through caspase activation. Moreover, the disruption of 26S proteasome activity induced by curcumin through inhibiting DYRK2 in different cancerous cells resulting in the inhibition of cell proliferation opens up a new horizon for using curcumin as a potential preventive and treatment approach in proteasome-linked cancers. This review presents a brief summary of knowledge about the mechanism of epigenetic changes induced by curcumin and the potential effects of curcumin such as anti-oxidant activity, enhancement of wound healing, modulation of angiogenesis and its interaction with inflammatory cytokines. The development of curcumin as a clinical molecule for successful chemo-prevention and alternate therapeutic approach needs further mechanistic insights.

Prospects of HSP70 as a genetic marker for thermo-tolerance and immuno-modulation in animals under climate change scenario.

Heat stress induced by long periods of high ambient temperature decreases animal productivity, leading to heavy economic losses. This devastating situation for livestock production is even becoming worse under the present climate change scenario. Strategies focused to breed animals with better thermo-tolerance and climatic resilience are keenly sought these days to mitigate impacts of heat stress especially in high input livestock production systems. The 70-kDa heat shock proteins (HSP70) are a protein family known for its potential role in thermo-tolerance and widely considered as cellular thermometers. HSP70 function as molecular chaperons and have major roles in cellular thermotolerance, apoptosis, immune-modulation and heat stress. Expression of HSP70 is controlled by various factors such as, intracellular pH, cyclic adenosine monophosphate (cyclic AMP), protein kinase C and intracellular free calcium, etc. Over expression of HSP70 has been observed under oxidative stress leading to scavenging of mitochondrial reactive oxygen species and protection of pulmonary endothelial barrier against bacterial toxins. Polymorphisms in flanking and promoter regions in HSP70 gene have shown association with heat tolerance, weaning weight, milk production, fertility and disease susceptibility in livestock. This review provides insight into pivotal roles of HSP70 which make it an ideal candidate genetic marker for selection of animals with better climate resilience, immune response and superior performance.

Yersinia enterocolitica-Specific Infection by Bacteriophages TG1 and ϕR1-RT Is Dependent on Temperature-Regulated Expression of the Phage Host Receptor OmpF.

UNLABELLED: Bacteriophages present huge potential both as a resource for developing novel tools for bacterial diagnostics and for use in phage therapy. This potential is also valid for bacteriophages specific for Yersinia enterocolitica To increase our knowledge of Y. enterocolitica-specific phages, we characterized two novel yersiniophages. The genomes of the bacteriophages vB_YenM_TG1 (TG1) and vB_YenM_ϕR1-RT (ϕR1-RT), isolated from pig manure in Canada and from sewage in Finland, consist of linear double-stranded DNA of 162,101 and 168,809 bp, respectively. Their genomes comprise 262 putative coding sequences and 4 tRNA genes and share 91% overall nucleotide identity. Based on phylogenetic analyses of their whole-genome sequences and large terminase subunit protein sequences, a genus named Tg1virus within the family Myoviridae is proposed, with TG1 and ϕR1-RT (R1RT in the ICTV database) as member species. These bacteriophages exhibit a host range restricted to Y. enterocolitica and display lytic activity against the epidemiologically significant serotypes O:3, O:5,27, and O:9 at and below 25°C. Adsorption analyses of lipopolysaccharide (LPS) and OmpF mutants demonstrate that these phages use both the LPS inner core heptosyl residues and the outer membrane protein OmpF as phage receptors. Based on RNA sequencing and quantitative proteomics, we also demonstrate that temperature-dependent infection is due to strong repression of OmpF at 37°C. In addition, ϕR1-RT was shown to be able to enter into a pseudolysogenic state. Together, this work provides further insight into phage-host cell interactions by highlighting the importance of understanding underlying factors which may affect the abundance of phage host receptors on the cell surface. IMPORTANCE: Only a small number of bacteriophages infecting Y. enterocolitica, the predominant causative agent of yersiniosis, have been previously described. Here, two newly isolated Y. enterocolitica phages were studied in detail, with the aim of elucidating the host cell receptors required for infection. Our research further expands the repertoire of phages available for consideration as potential antimicrobial agents or as diagnostic tools for this important bacterial pathogen.

Identification of essential regulatory elements responsible for the explicit expression of IL-28Rα and their effect on critical SNPs using in-Silico methods.

IL-28Rα and IL10Rß collectively construct a fully functional hetero-dimeric receptor for type III interferons (IFNs). IL-28Rα is the private chain for type III IFNs since their involvement in any other pathway has not been reported yet and they are highly expressed in response to certain viral attack or cancers. IL-28Rα is specific in their expression pattern and it expresses within few cell types only. The regulatory mechanisms governing the expression of IL-28Rα at the molecular level are not completely known yet and need to be scrutinized at primary levels. In the present study, various in-silico techniques were applied and it was observed that AP1-2, STAT 1-6, P-53, LyF-1 (lymphoid transcription factor), c-Jun, PU.1, CREB (cAMP response element-binding), PLAG (pleotropic adenoma gene), MYOD (myoblast determination protein 1), NOFL and KLFS as transcription factors that are selected with preference. Interestingly AP-2, c-Jun, LyF-1, STAT, NF-Y and P53 have also been reported in literature recently as some of the key regulatory elements as well. Based on the fact that interlinking between different interferon stimulation genes (ISGs) is also not very clear and induction of one type of interferon can affect the efficacy of the other, we found that IFN-λ4 induction can increase the expression of IL-28Rα, similar to IFN-λ3 but contrary to type I IFNs, which has either no effect on the expression of IL-28Rα or can down regulate its expression at higher concentrations (data not published).