Knowledge and attitudes of primary care nurses towards geriatric depression in Jazan Region, Saudi Arabia.

Depression is a global health concern, particularly in the geriatric population. The increasing number of hospital admissions among older individuals highlights the need for healthcare professionals, particularly nurses, to understand and treat geriatric depression. Nurses play a crucial role in caring for older adults with depressive symptoms or depression. This study aimed to assess knowledge and attitudes regarding geriatric depression among primary care nurses in Jazan Region, Saudi Arabia. A cross-sectional study was conducted among 210 primary healthcare nurses in Jazan City using a validated self-administered questionnaire. Knowledge scores were measured and compared among selected demographic variables as well as attitudes toward geriatric depression. Data obtained were analyzed using the Statistical Package for the Social Sciences, version. 20.0. Chi-square test, fisher's exact test were used for comparison of variables with categorical data. Most primary care nurses were interested in caring for older patients with depression; however, they never attended training courses focused on geriatric depression. Where the study indicated that 38.1% of participants have poor knowledge about geriatric depression while 25.2% have good knowledge. Where the majority had a high understanding of the potential side effects of antidepressant medications, while they had limited knowledge about symptoms, diagnosis, and medications, the majority of participants demonstrated a positive attitude regarding feeling comfortable dealing with depressed patients' needs (56.7%) and considered their profession as a well-placed to assist patients (83.3%) However, 15.2% had a negative attitude citing a lack of self-discipline and willpower.

La dépression est un problème de santé mondial, en particulier dans la population gériatrique. Le nombre croissant d'hospitalisations chez les personnes âgées met en évidence la nécessité pour les professionnels de santé, en particulier les infirmières, de comprendre et de traiter la dépression gériatrique. Les infirmières jouent un rôle crucial dans la prise en charge des personnes âgées présentant des symptômes dépressifs ou une dépression. Cette étude visait à évaluer les connaissances et les attitudes concernant la dépression gériatrique parmi les infirmières de soins primaires de la région de Jazan, en Arabie Saoudite. Une étude transversale a été menée auprès de 210 infirmières de soins primaires de la ville de Jazan à l'aide d'un questionnaire auto-administré validé. Les scores de connaissances ont été mesurés et comparés parmi certaines variables démographiques ainsi que les attitudes à l'égard de la dépression gériatrique. Les données obtenues ont été analysées à l'aide du progiciel statistique pour les sciences sociales, version. 20,0. Le test du Chi carré et le test exact de Fisher ont été utilisés pour comparer les variables avec les données catégorielles. La plupart des infirmières de soins primaires souhaitaient soigner des patients âgés souffrant de dépression ; cependant, ils n'ont jamais suivi de formation axée sur la dépression gériatrique. L'étude indique que 38,1 % des participants ont de mauvaises connaissances sur la dépression gériatrique tandis que 25,2 % ont de bonnes connaissances. Alors que la majorité des participants avaient une bonne compréhension des effets secondaires potentiels des médicaments antidépresseurs, alors qu'ils avaient une connaissance limitée des symptômes, du diagnostic et des médicaments, la majorité des participants ont démontré une attitude positive et se sentaient à l'aise pour répondre aux besoins des patients déprimés (56,7 %). et considéraient leur profession comme bien placée pour assister les patients (83,3 %). Toutefois, 15,2 % avaient une attitude négative citant un manque d'autodiscipline et de volonté.

Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability.

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives.

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

Ononin: A comprehensive review of anticancer potential of natural isoflavone glycoside.

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.

The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget.

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

Multirole of the internet of medical things (IoMT) in biomedical systems for managing smart healthcare systems: An overview of current and future innovative trends.

Internet of Medical Things (IoMT) is an emerging subset of Internet of Things (IoT), often called as IoT in healthcare, refers to medical devices and applications with internet connectivity, is exponentially gaining researchers' attention due to its wide-ranging applicability in biomedical systems for Smart Healthcare systems. IoMT facilitates remote health biomedical system and plays a crucial role within the healthcare industry to enhance precision, reliability, consistency and productivity of electronic devices used for various healthcare purposes. It comprises a conceptualized architecture for providing information retrieval strategies to extract the data from patient records using sensors for biomedical analysis and diagnostics against manifold diseases to provide cost-effective medical solutions, quick hospital treatments, and personalized healthcare. This article provides a comprehensive overview of IoMT with special emphasis on its current and future trends used in biomedical systems, such as deep learning, machine learning, blockchains, artificial intelligence, radio frequency identification, and industry 5.0.

Etiology and incidence of postpartum depression among birthing women in the scenario of pandemics, geopolitical conflicts and natural disasters: a systematic review.

Postpartum depression (PPD) is classified under postpartum psychiatric disorders and initiates soon after birthing, eliciting neuropsychological and behavioral deficits in mothers and offspring. Globally, PPD is estimated to be associated with 130-190 per 1000 birthing. The severity and incidences of PPD have aggravated in the recent years due to the several unfavorable environmental and geopolitical circumstances. The purpose of this systematic review hence is to explore the contributions of recent circumstances on the pathogenesis and incidence of PPD. The search, selection and retrieval of the articles published during the last three years were systematically performed. The results from the primary studies indicate that unfavorable contemporary socio-geopolitical and environmental circumstances (e.g. Covid-19 pandemic, political conflicts/wars, and natural calamities; such as floods and earthquakes) detrimentally affect PPD etiology. A combination of socio-economic and psychological factors, including perceived lack of support and anxiousness about the future may contribute to drastic aggravation of PPD incidences. Finally, we outline some of the potential treatment regimens (e.g. inter-personal psycho- and art-based therapies) that may prove to be effective in amelioration of PPD-linked symptoms in birthing women, either alone or in complementation with traditional pharmacological interventions. We propose these psychological and art-based intervention strategies may beneficially counteract the negative influences of the unfortunate recent events across multiple cultures, societies and geographical regions.

Critical appraisal and systematic review of genes linked with cocaine addiction, depression and anxiety.

Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.

Comprehensive deep mutational scanning reveals the pH induced stability and binding differences between SARS-CoV-2 spike RBD and human ACE2.

The SARS-CoV-2 spike (S) glycoprotein with its mobile receptor-binding domain (RBD), binds to the human ACE2 receptor and thus facilitates virus entry through low-pH-endosomal pathways. The high degree of SARS-CoV-2 mutability has raised concern among scientists and medical professionals because it created doubt about the effectiveness of drugs and vaccinations designed specifically for COVID-19. In this study, we used computational saturation mutagenesis approach, including structure-based free energy calculations to analyse the effects of the missense mutations on the SARS-CoV-2 S-RBD stability and the S-RBD binding affinity with ACE2 at three different pH (pH 4.5, pH 6.5, and pH 7.4). A total of 3705 mutations in the S-RBD protein were analyzed, and we discovered that most of these mutations destabilize the RBD protein. Specifically, residues G404, G431, G447, A475, and G526 were important for RBD protein stability. In addition, RBD residues Y449, Y489, Y495, Q498, and N487 were critical for the RBD-ACE2 interaction. Next, we found that the distribution of the mean stability changes and mean binding energy changes of RBD due to mutations at both serological and endosomal pH correlated well, indicating the similar effects of mutations. Overall, this computational analysis is useful for understanding the effects of missense mutations in SARS-CoV-2 pathogenesis at different pH.Communicated by Ramaswamy H. Sarma.

In silico identification of microRNAs targeting the PPARα/γ: promising therapeutics for SARS-CoV­2 infection.

The SARS-CoV-2 lifecycle is dependent on the host metabolism machinery. It upregulates the PPARα and PPARγ genes in lipid metabolism, which supports the essential viral replication complex including lipid rafts and palmitoylation of viral protein. The use of PPAR ligands in SARS-CoV-2 infection may have positive effects by preventing cytokine storm and the ensuing inflammatory cascade. The inhibition of PPARα and PPARγ genes may alter the metabolism and may disrupt the lifecycle of SARS-CoV-2 and COVID-19 progression. In the present work, we have identified possible miRNAs targeting PPARα and PPARγ in search of modulators of PPARα and PPARγ genes expression. The identified miRNAs could possibly be viewed as new therapeutic targets against COVID-19 infection.

In silico evaluation of the inhibitory potential of nucleocapsid inhibitors of SARS-CoV-2: a binding and energetic perspective.

The COVID-19 outbreak brought on by the SARS-CoV-2 virus continued to infect a sizable population worldwide. The SARS-CoV-2 nucleocapsid (N) protein is the most conserved RNA-binding structural protein and is a desirable target because of its involvement in viral transcription and replication. Based on this aspect, this study focused to repurpose antiviral compounds approved or in development for treating COVID-19. The inhibitors chosen are either FDA-approved or are currently being studied in clinical trials against COVID-19. Initially, they were designed to target stress granules and other RNA biology. We have utilized structure-based molecular docking and all-atom molecular dynamics (MD) simulation approach to investigate in detail the binding energy and binding modes of the different anti-N inhibitors to N protein. The result showed that five drugs including Silmitasterib, Ninetanidinb, Ternatin, Luteolin, Fedratinib, PJ34, and Zotatafin were found interacting with RNA binding sites as well as to predicted protein interface with higher binding energy. Overall, drug binding increases the stability of the complex with maximum stability found in the order, Silmitasertib > PJ34 > Zotatatafin. In addition, the frustration changes due to drug binding brings a decrease in local frustration and this decrease is mainly observed in α-helix, ß3, ß5, and ß6 strands and are important for drug binding. Our in-silico data suggest that an effective interaction occurs for some of the tested drugs and prompt their further validation to reduce the rapid outspreading of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 origins: zoonotic Rhinolophus vs contemporary models.

The question of the origin of coronavirus spread like wildfire ever since it wreaked havoc among humankind, and ever since the scientific community has worked tirelessly to trace the history of the virus. In this review, we have tried to compile relevant literature pertaining to the different theories of origin of SARS-CoV-2, hopefully without any bias, and we strongly support the zoonotic origin of the infamous SARS-CoV-2 in bats and its transfer to human beings through the most probable evolutionary hosts, pangolins and minks. We also support the contemporary 'Circulation Model' that simply mirrors the concept of evolution to explain the origin of the virus which, the authors believe, is the most rational school of thought. The most recent variant of SARS-CoV-2, Omicron, has been taken as an example to clarify the concept. We recommend the community to refer to this model for further understanding and delving deep into this mystery of the origin of SARS-CoV-2.

Bioplatforms in liquid biopsy: advances in the techniques for isolation, characterization and clinical applications.

Tissue biopsy analysis has conventionally been the gold standard for cancer prognosis, diagnosis and prediction of responses/resistances to treatments. The existing biopsy procedures used in clinical practice are, however, invasive, painful and often associated with pitfalls like poor recovery of tumor cells and infeasibility for repetition in single patients. To circumvent these limitations, alternative non-invasive, rapid and economical, yet sturdy, consistent and dependable, biopsy techniques are required. Liquid biopsy is an emerging technology that fulfills these criteria and potentially much more in terms of subject-specific real-time monitoring of cancer progression, determination of tumor heterogeneity and treatment responses, and specific identification of the type and stages of cancers. The present review first briefly revisits the state-of-the-art technique of liquid biopsy and then proceeds to address in detail, the advances in the potential clinical applications of four major biological agencies present in liquid biopsy samples (circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs)). Finally, the authors conclude with the limitations that need to be addressed in order for liquid biopsy to effectively replace the conventional invasive biopsy methods in the clinical settings.

Network-based approach for targeting human kinases commonly associated with amyotrophic lateral sclerosis and cancer.

Background: Amyotrophic Lateral Sclerosis (ALS) is a rare progressive and chronic motor neuron degenerative disease for which at present no cure is available. In recent years, multiple genes encode kinases and other causative agents for ALS have been identified. Kinases are enzymes that show pleiotropic nature and regulate different signal transduction processes and pathways. The dysregulation of kinase activity results in dramatic changes in processes and causes many other human diseases including cancers. Methods: In this study, we have adopted a network-based system biology approach to investigate the kinase-based molecular interplay between ALS and other human disorders. A list of 62 ALS-associated-kinases was first identified and then we identified the disease associated with them by scanning multiple disease-gene interaction databases to understand the link between the ALS-associated kinases and other disorders. Results: An interaction network with 36 kinases and 381 different disorders associated with them was prepared, which represents the complexity and the comorbidity associated with the kinases. Further, we have identified 5 miRNAs targeting the majority of the kinases in the disease-causing network. The gene ontology and pathways enrichment analysis of those miRNAs were performed to understand their biological and molecular functions along with to identify the important pathways. We also identified 3 drug molecules that can perturb the disease-causing network by drug repurposing. Conclusion: This network-based study presented hereby contributes to a better knowledge of the molecular underpinning of comorbidities associated with the kinases associated with the ALS disease and provides the potential therapeutic targets to disrupt the highly complex disease-causing network.