Different modalities to manage rheumatoid arthritis: an A to Z story.

Aim: To investigate different approaches to RA treatment that might lead to greater efficacy and better safety profiles. Methods: The Search strategy was based on medical subject headings, and screening and selection were based on inclusion/exclusion criteria. Results & discussion: Early therapy is critical for disease control and loss of bodily function. The most promising outcomes came from the development of disease-modifying anti-rheumatic drugs. Different foods have anti-inflammatory and antioxidant qualities that protect against the development of rheumatoid arthritis (RA). Some dietary patterns and supplements have been shown to have potential protective benefits against RA. Conclusion: Improvement in the quality of life of RA patients requires a tailored management approach based on the current patient medical data.

Rheumatoid arthritis is a complex disease with an unclear origin that affects the joints. In this systematic review, we aimed to investigate different effective ways of treating rheumatoid arthritis. Study results indicate that rheumatoid arthritis treatment requires coordination between different healthcare teams. As much as we can, when we start disease treatment early, this will lead to a better disease cure. Different drugs showed promising results in the treatment of rheumatoid arthritis, but the most promising treatment results came from a group of medicinal agents called 'disease-modifying anti-rheumatic drugs'. Different foods have anti-inflammatory and antioxidant effect and help in protection against rheumatoid arthritis, but others, such as red meat and salt, have the opposite effect. Some dietary patterns and supplements, such as the Mediterranean Diet, vitamin D and probiotics, have been shown to have potential protective benefits against rheumatoid arthritis. Improvement in the quality of patient life requires an individualized management roadmap based on current patient medical data.

Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights.

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.

Prevalence of Depression Among the Adult Population in Southwestern Saudi Arabia: A Cross-Sectional, Community-Based Study.

Background Depression is one of the most common mental disorders, which is increasing globally with higher prevalence among women. Many factors contribute to the etiology and risk factors for depression, including biological and psychosocial factors. This study aimed to assess the prevalence of depression among the adult population in Al-Qunfudah governorate, southwestern Saudi Arabia (SA). Methods A cross-sectional study was conducted on a sample of 1036 participants among adults in Al-Qunfudah governorate, southwestern SA, using a validated Arabic version of the Patient Health Questionnaire (PHQ-9) during the period from October 1st, 2022 to the end of December 2022. The PHQ-9 contains nine items, with a total score ranging from 0 to 27. A score of 1-4 represented minimal depression, while a score of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. The sample size was estimated to be 375 participants, by considering a margin of error of 5%, and a 95% confidence interval, calculated using Raosoft calculator (Raosoft Inc., Seattle, WA). Data collection was performed through an online survey of the PHQ-9 on a Google form and distributed using different social media platforms. The eligible participants' responses were kept confidential and analyzed using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). p-values of <0.05 were considered statistically significant.  Results The study showed that the overall prevalence of depression among the 1036 adult study participants was 68.1%. Mild, moderate, moderate to severe, and severe depression was diagnosed among 28.2%, 21.9%, 12%, and 6% of the participants, respectively. Several factors were significantly associated with PHQ-9 diagnosed depression including being younger (p<0.0001), a female (p<0.0001), single (p<0.0001), a student (p<0.0001), and non-employed (p<0.0001) and having a lower educational level (p<0.0001). Conclusions There is a high prevalence rate of depression among the adult population of Al-Qunfudah governorate in southwestern SA, which highlights the need for interventions to address this issue, and to reduce the incidence of depression in the region among the high-risk groups.

Nonallergic Rhinopathy: A Comprehensive Review of Classification, Diagnosis, and Treatment.

Chronic nonallergic rhinitis syndromes encompass various conditions, of which vasomotor rhinitis is the most common form, representing approximately 80% of patients, also referred to as nonallergic rhinopathy (NAR), nasal hyperreactivity, neurogenic rhinitis, or idiopathic rhinitis. Expert panels have recommended replacing vasomotor rhinitis terminology because it is more descriptive of this condition that is characterized by symptoms triggered by chemical irritants and weather changes through chemosensors, mechanosensors, thermosensors, and/or osmosensors activated through different transient receptor potential calcium ion channels. Elucidating the specific role of transient receptor potential vanilloid 1, triggered by capsaicin, has been an important advancement in better understanding the pathophysiology of NAR because it has now been shown that downregulation of transient receptor potential vanilloid 1 receptors by several therapeutic compounds provides symptomatic relief for this condition. The classification of NAR is further complicated by its association with allergic rhinitis referred to as mixed rhinitis, which involves both immunoglobulin E-mediated and neurogenic mechanistic pathways. Comorbidities associated with NAR, including rhinosinusitis, headaches, asthma, chronic cough, and sleep disturbances, underscore the need for comprehensive management. Treatment options for NAR include environmental interventions, pharmacotherapy, and in refractory cases, surgical options, emphasizing the need for a tailored approach for each patient. Thus, it is extremely important to accurately diagnose NAR because inappropriate therapies lead to poor clinical outcomes and unnecessary health care and economic burdens for these patients. This review provides a comprehensive overview of NAR subtypes, focusing on classification, diagnosis, and treatment approaches for NAR.

Knowledge, Attitude, and Practice of Adult Diabetics Regarding Diabetic Foot Ulcers: A Cross-Sectional Study in Saudi Arabia.

Background Diabetic foot ulcers (DFUs) are one of the most common and fatal complications of diabetic patients with uncontrolled diabetes mellitus (DM) that may end with their feet amputation. These complications can be prevented through the adherence of diabetic patients to their diabetes management plan and by educating them about risk factors, complications of diabetic foot, and proper foot care. To develop effective health education programs to educate diabetic patients and caregivers regarding diabetic foot and its effective care, we should first identify gaps in patients' knowledge and perception of diabetic foot and evaluate their practice of foot care. Objectives This study aimed to evaluate knowledge and attitude toward DFUs and the practice of foot care among adult diabetic patients attending Al-Qunfudah Diabetes Center, Saudi Arabia, from October 2022 to March 2023. Methods A total of 403 adult diabetic patients were recruited in this cross-sectional study during their attendance at the diabetes center in Al-Qunfudah district, Saudi Arabia. The study researchers conducted a physical face-to-face interview with each diabetic patient using a validated questionnaire with closed-ended questions to collect their responses regarding their knowledge and attitude toward DFUs and their behavior toward foot care. The collected data were analyzed using IBM SPSS Statistics for Windows, version 23 (released 2015; IBM Corp., Armonk, New York, United States). Results Out of 403 diabetics, 50.4% (n = 203) had inadequate knowledge (knowledge score < 80%), 46.4% (n = 187) had negative attitudes (attitude score < 80%) toward DFUs, and the majority could not practice foot care well, with 77.7% (n = 313) giving a practice score less than 80%. Seventy patients (17.4%) self-reported a history of DFUs. Predictors of good knowledge about DFUs among diabetics include age between 30 and 59 years (odds ratio (OR) = 2.942, confidence interval (CI) 95% = 1.695-2.107, p < 0.001), marriage (OR = 3.101, CI 95% = 1.893-5.079, p < 0.001), working (OR = 5.325, CI 95% = 3.019-9.389, p < 0.001), diploma education (OR = 8.205, CI 95% = 3.332-20.203, p < 0.001), managing DM with oral drugs (OR = 2.219, CI 95% = 1.399-3.519, p < 0.001), and having no DFUs (OR = 2.712, CI 95% = 1.557-4.723, p < 0.001). Males were more likely to practice foot care well (OR = 1.925, CI 95% = 1.142-3.245, p = 0.013). Primary education (OR = 3.421, CI 95% = 1.655-7.073, p < 0.001) predicted appropriate foot care. Patients with DM for one to five years (OR = 1.995, CI 95% = 1.139-3.493, p = 0.016) and those on diet and metformin (OR = 2.133, CI 95% = 1.134-4.011, p = 0.019) were expected to have better foot care than other diabetics. Conclusion Diabetic patients in the Al-Qunfudah district of Saudi Arabia had inadequate knowledge and negative attitudes toward DFUs, and their foot care behaviors were inadequate. Furthermore, DFUs were self-reported in around 17% of diabetic patients. Specialized training programs are recommended to enhance knowledge regarding DFUs among diabetics and motivate and train them and caregivers on how to conduct proper foot care. These educational programs should target all diabetics, with an emphasis on those with DFUs, females, non-working patients, individuals who have had DM for a longer time, and illiterate diabetics. To understand the factors behind patients' negative attitudes toward diabetic foot, future qualitative research is required.

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Plain Language Summary: Immunotherapy for Inhalant Allergy.

The plain language summary explains allergen immunotherapy to patients, families, and caregivers. The summary is for patients aged 5 years and older who are experiencing symptoms from inhalant allergies and are considering immunotherapy as a treatment option. It is based on the 2024 "Clinical Practice Guideline: Immunotherapy for Inhalant Allergy." This plain language summary is a companion publication to the full guideline, which provides greater detail for health care providers. Guidelines and their recommendations may not apply to every patient, but they can be used to find best practices and quality improvement opportunities.

mecA and fdh: markers of pathogenicity and commensalism in Staphylococcus epidermidis of pediatric origin from Pakistan.

Staphylococcus epidermidis is an opportunistic bacterial pathogen. The study screened isolates of S. epidermidis of pediatric origin for genetic markers of discriminatory potential. 103 isolates (n = 75 clinical; n = 28 community) were screened for methicillin resistance (mecA), formate dehydrogenase (fdh) and an array of virulence factors through multiplex PCR and Congo red assay. The isolates were typed in four distinct categories, based on the presence of selected virulent factors. The type A clinical isolates carrying icaADBC operon (n = 22; 29.3%, P = 0.117) were not significantly differentiating the origin of isolates. The type B clinical isolates representing methicillin resistant S. epidermidis (MRSE) (n = 73; 97.3%, P < 0.00001) and the type C clinical isolates lacking formate dehydrogenase fdh (n = 62; 82.6%, P < 0.00001) were having significant discriminatory potential of clinical isolates, respectively. All type D community isolates were carrying fdh (n = 28; 100%, P < 0.00001). MecA and fdh are significant differential markers of pathogenicity and commensalism in S. epidermidis of pediatric origin.

Prevalence and impact of long COVID-19 among patients with diabetes and cardiovascular diseases in Bangladesh.

Introduction: Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh. Methods: We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival. Results: COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79-4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients. Discussion: Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh.

Knowledge, Attitude, and Practice of Parents Regarding Children's Eye Care in Al-Qunfudah Governorate, Saudi Arabia.

BACKGROUND: Visual impairment and blindness have a long-term impact on children. Common causes include refractive error, amblyopia, and cataracts, all of which are preventable. OBJECTIVES: This study aims to evaluate the knowledge, attitude, and practice of parents regarding children's eye care in Al-Qunfudah governorate, Saudi Arabia. METHODS: A cross-sectional study was carried out on a convenience sample of 403 parents residing in the governorate of Al-Qunfudah. Data were gathered using a validated, self-administered online questionnaire that required participants' consent and ensured data confidentiality. IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States) was used to do the statistical analysis of the data. RESULTS: This study included 403 participants; 41.2% of them were 36-45 years old, 75.9% were female, and 88.8% were married. Most of the participants had had their children undergo eye examinations (65%). A positive attitude about child eye care among the participants was observed in 48.9% of them, while the level of knowledge about eye care and its regular examinations was poor in 60% of the study sample. A significant positive correlation was detected between participants' attitudes and knowledge scores about the eye care of their children (r = 0.238, p-value = <0.001). Older adults (P = 0.004), those with employment (P = 0.004), and those with a history of children suffering from eye problems (P = 0.018) are associated with a positive attitude, while better knowledge is associated with the parent's age (P = 0.007) and higher education level (P = 0.047). CONCLUSION: The knowledge and attitude of the parents regarding their children's eye care were suboptimal, and the main reason for conducting eye examinations on their children was the presence of active eye disease and a symptomatic child. Positive attitudes were more prevalent among those aged 36-45 years, employed, and with a higher number of children with eye problems. Those in the age group of 36-45 who had a bachelor's degree were associated with greater knowledge. There is an urgent need to educate parents about routine and recommended eye screening. Family physicians should conduct opportunistic eye screenings for children who attend primary healthcare facilities and provide parents with educational materials about common eye disorders and children's eye care.

Comparative Evaluation of Salivary Parameters in Tobacco Substance Abusers.

BACKGROUND: Tobacco use by youth is ever-demanding, and it is increasingly distributed not only in India but also globally. Saliva is a complex oral bio-fluid, freely available, performing absolute tasks for maintaining oral health and homeostasis. It contains a plethora of significant constituents such as proline-rich proteins (PRPs), immunoglobulins, IgA, enzymes lysozyme, lactoferrin, peroxidases, amylase, etc. The basic ecological balance of the oral cavity is stabilized via salivary clearance by reduced aggregation and adherence of microorganisms by direct microbial activity. This balance of oral activity is also done by indirect mechanisms by immunological as well as non-immunological means and also by effectively regulating salivary pH flow rate. This institutional observational study was planned to assess and compare salivary parameters (pH, salivary flow rate), total proteins, α-amylase, calcium, phosphate, and IgA, of unstimulated whole saliva of both tobacco abusers and tobacco non-users. METHODS: The Study consisted of 270 participants (Tobacco habit) group, n = 135 and Control (Healthy) group, n = 135 and were in the age range of 20-50 years. They were assessed for oral health status, followed by the analysis of salivary pH, flow rate, total proteins, amylase, calcium, phosphates, and IgA of unstimulated whole saliva. RESULTS: Comparative evaluation of salivary parameters among groups found that varying tobacco abusers had increased salivary amylase, protein levels, and phosphate whereas decreased salivary pH, flow rate, IgA, and in the whole unstimulated saliva samples than those of non-tobacco users. This difference among groups was statistically significant. (p < 0.05), and calcium levels were not altered significantly. CONCLUSIONS: This study concludes that salivary parameters are altered in tobacco abusers when compared to those of non-abusers, and it was more significant in smokeless tobacco abusers than in any other form of tobacco abuse.

Molecular epidemiology, transmission and clinical features of 2022-mpox outbreak: A systematic review.

Background and Aims: The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer-reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022-mpox outbreak. Methods: We identified 45 peer-reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study. Results: The case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non-endemic regions. Men (70%-98% cases) were mostly infected with homosexual and bisexual behavior (30%-60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%-60% of cases were reported. Human-to-human transmission via direct contact and different body fluids were involved in the majority of the cases (90%-100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%-40%) and proctitis (20%-40%) were more common during 2022 outbreak than pre-2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre- and post-prophylaxis in cases. About 100% of the cases in non-endemic regions were associated with isolates of IIb clade with a divergence of 0.0018-0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10. Conclusion: This study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox.

Exploring the multi-gene regulatory molecular mechanism of Saudi Arabian flora against epilepsy based on data mining, network pharmacology and docking analysis.

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly affecting the population in Saudi Arabia across all age demographics. The global prevalence of active epilepsy is around 6.38/1,000 persons and in the Arabian region, the median prevalence of active epilepsy is 4.4/1,000 persons. However, over 75% of individuals are untreated. Consequently, the development of therapeutic strategies with increased efficacy and safety profiles is essential to improve the survival rate among epilepsy patients. The current study integrates network pharmacology along with Bioinformatics approaches to explore the potential molecular mechanisms of local flora of Saudi Arabia including Solanum incanum, Abrus precatorius, Withania somnifera, and Azadirachta indica in epilepsy treatment. In the preliminary phase, data related to the bioactive components of the local plants and the associated target genes of both these plants and epilepsy were gathered from scientific literature and open-source databases. This data was then analyzed to identify common targets between the plants and ovarian cancer. Based on these common targets, a protein-protein interaction (PPI) network was constructed utilizing the STRING database, which was subsequently incorporated into the Cytoscape software for identification of hub genes based on their degree of connectivity. Lastly, an interplay network depicting the associations between the compounds and the overlapping genes was formulated via Cytoscape, to study the potential network pharmacology implications of these active compounds in relation to ovarian cancer. Following that, a compound-target protein-pathway network was constructed which uncovered that namely abrectorin, genistin, (+)-catechin, precatorine, (+)-ascorbic acid, licoflavanone, skrofulein, stigmasterone, 5,7-Dihydroxy-4'-methoxy-8,3'-di-C-prenylflavanone could potentially be used as antagonists for the therapeutic management of epilepsy by targeting TNF and TP53 proteins. Furthermore, the implementation of molecular docking reinforces the binding affinity of the compound, indicating a robust stability of the forecasted compounds at the docked site. This research lays both a theoretical and experimental groundwork for more profound investigations and establishes a practical method for the strategic employment of active compounds in the development of anti-epileptic therapeutics.

Eleven Crucial Pesticides Appear to Regulate Key Genes That Link MPTP Mechanism to Cause Parkinson's Disease through the Selective Degeneration of Dopamine Neurons.

Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson's disease (PD) is unknown. Understanding the pesticide's effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA is hypothesized to activate a signaling cascade and accelerate degeneration. Using MPTP as a reference, we demonstrate the mechanisms of eleven crucial pesticides through molecular docking, protein networks, regulatory pathways, and prioritization of key pesticide-regulating proteins. Participants were recruited and grouped into control and PD based on clinical characteristics as well as pesticide traces in their blood plasma. Then, qPCR was used to measure pesticide-associated gene expression in peripheral blood mononuclear cells between groups. As a result of molecular docking, all eleven pesticides and the MPTP showed high binding efficiency against 274 membrane receptor proteins of DA. Further, the protein interaction networks showed activation of multiple signaling cascades through these receptors. Subsequent analysis revealed 31 biological pathways shared by all 11pesticides and MPTP that were overrepresented by 46 crucial proteins. Among these, CTNNB1, NDUFS6, and CAV1 were prioritized to show a significant change in gene expression in pesticide-exposed PD which guides toward therapy.

Effects of Bacterial Metabolites on the Wnt4 Protein in Dental-Pulp-Stem-Cells-Based Endodontic Pulpitis Treatment.

Porphyromonas gingivalis is associated with endodontic pulpitis, causing damage to the dental pulp, leading to severe pain and a decline in quality of life. Regenerative pulp treatments using dental pulp stem cells (DPSCs) can be hindered by interactions between DPSCs and the infecting bacteria. The protein WNT family member 4 (Wnt4) plays a critical role in the differentiation of DPSCs and the regeneration of odontogenic tissue. However, the specific influence of P. gingivalis on Wnt4 remains unclear. In this study, we employed a computational approach to investigate the underlying mechanisms through which P. gingivalis-produced metabolites inhibit the Wnt4 protein, thereby diminishing the regenerative potential and therapeutic efficacy of odontogenic tissue. Among the metabolites examined, C29H46N7O18P3S-4 exhibited the strongest inhibitory effect on the Wnt4 protein, as evidenced by the lowest binding energy score of -6782 kcal/mol. Molecular dynamic simulation trajectories revealed that the binding of C29H46N7O18P3S-4 significantly altered the structural dynamics and stability of the Wnt4 protein. These alterations in protein trajectories may have implications for the molecular function of Wnt4 and its associated pathways. Overall, our findings shed light on the inhibitory impact of P. gingivalis-produced metabolites on the Wnt4 protein. Further in vitro, in vivo, and clinical studies are necessary to validate and expand upon our findings.

Virtual screening, molecular dynamics and density functional theory on pain inhibitors against TRPV1 associating inflammatory conditions.

Transient receptor potential vanilloid 1 protein (TRPV1) is expressed widely in skin and sensory neurons that contribute to pain/heat sensation in the human system. TRPV1 gene polymorphisms are susceptible to multiple diseases and it is considered a therapeutic target for various inflammatory conditions. Among the TRPV1 variants, rs8065080 (1911 A > G) plays a vital role in painful osteoarthritis and migraine. The presence of rs8065080 polymorphism may render drug efficacy. This study aimed to identify better antagonists against wild-type and variant TRPV1 that may help in the relief of pain/inflammation. We constructed suitable TRPV1 protein structures for wild-type and rs8065080 variant through a homology modelling approach. A total of 3363 anti-inflammatory compounds with high chemical diversity and good drug-like properties were collected and screened against the generated structures. Molecular docking showed that nobilamide B had the highest binding affinity (-5.83 kcal/mol) towards the wild-type. Whereas, isoquinoline analogue displayed highest binding potency with the variant TRPV1 (-11.65 kcal/mol). Besides those, C18H15F3N4O showed affinity towards both wild-type (-5.53 kcal/mol) and variant TRPV1 (-9.75 kcal/mol). Then, molecular dynamic simulation revealed stable conformation in wild-type and variant TRPV1 upon binding of nobilmaide B, isoquinoline analogue and C18H15F3N4O. Additionally, density functional theory (DFT) using B3LYP hybrid function showed high chemical reactiveness of nobilamie B, isoquinoline analogue and C18H15F3N4O. Overall, our systematic investigations provide, C18H15F3N4O could be a potential analgesic inhibiting both wild-type and variant TRPV1 against inflammatory conditions.

Magnitude and predictors of anemia among preschool children (36-59 months) in Atingo town, Jimma, Ethiopia.

Introduction: Anemia is a serious public health concern that affects more than 25% of the world's population. It is still widespread and at its most severe in Ethiopia. This study pointed to identify the magnitude and predictors of anemia in preschool children in Atinago. Method: A structured interview and anthropometric metrics had been used in a cross-sectional study to collect data from 309 preschool children using a systematic sampling strategy from May 10 to June 25, 2022. Frequencies, percentages, means, and a bar chart were created as descriptive statistics. Factors that were significant at the 25% level in univariate analysis were run through multiple logistic models. Odds ratios with respective 95% confidence intervals were developed to determine the relevant predictors. Result: The majority (51.7%) of preschool children in Atinago town had anemia. The finding reveals that poor dietary diversity (adjusted odds ratio [AOR] = 1.77, 95% confidence interval [CI] = 1.02-3.07), children from families with food insecurity (AOR = 2.28, 95% CI = 1.31-3.9), child-mothers used iron folate for less than 3 months during pregnancy (AOR = 1.93, 95% CI = 1.07-3.48), households with more than five children (AOR = 1.880, 95% CI = 1.12-3.18), and stunted children (AOR = 1.78, 95% CI = 1.05-3.01) were highly susceptible to anemia. Conclusion: The findings indicate that anemia was a serious issue among preschool children in Atinago. Therefore, stakeholders should provide community-based nutrition training on consuming diverse diets, dietary improvements in the home, consuming iron-rich meals, and the like; encourage mothers to participate in early ANC follow-up; and strengthen activities aimed at identifying households with food insecurity status.

Assessment of Demographic Changes of Workforce Diversity in Otolaryngology, 2013 to 2022.

Importance: Given the growth of minoritized groups in the US and the widening racial and ethnic health disparities, improving diversity remains a proposed solution in the field of otolaryngology. Evaluating current trends in workforce diversity may highlight potential areas for improvement. Objective: To understand the changes in gender, racial, and ethnic diversity in the otolaryngology workforce in comparison with changes in the general surgery and neurosurgery workforces from 2013 to 2022. Design, Setting, and Participants: This cross-sectional study used publicly available data from the Accreditation Council for Graduate Medical Education and the Association of American Medical Colleges for 2013 to 2022, and included medical students and trainees in all US medical residency programs and allopathic medical schools. Main Outcomes and Measures: Average percentages of women, Black, and Latino trainees during 2 intervals of 5 years (2013-2017 and 2018-2022). Pearson χ2 tests compared demographic information. Normalized ratios were calculated for each demographic group in medical school and residency. Piecewise linear regression assessed linear fit for representation across time periods and compared rates of change. Results: The study population comprised 59 865 medical residents (43 931 [73.4%] women; 6203 [10.4%] Black and 9731 [16.2%] Latino individuals; age was not reported). The comparison between the 2 study intervals showed that the proportions of women, Black, and Latino trainees increased in otolaryngology (2.9%, 0.7%, and 1.6%, respectively), and decreased for Black trainees in both general surgery and neurosurgery (-0.4% and -1.0%, respectively). In comparison with their proportions in medical school, Latino trainees were well represented in general surgery, neurosurgery, and otolaryngology (normalized ratios [NRs]: 1.25, 1.06, and 0.96, respectively); however, women and Black trainees remained underrepresented in general surgery, neurosurgery, and otolaryngology (women NRs, 0.76, 0.33, and 0.68; Black NRs, 0.63, 0.61, and 0.29, respectively). The percentage of women, Black, and Latino trainees in otolaryngology all increased from 2020 to 2022 (2.5%, 1.1%, and 1.1%, respectively). Piecewise regression showed positive trends across all 3 specialties. Conclusions and Relevance: The findings of this cross-sectional study indicate a positive direction but only a modest increase of diversity in otolaryngology, particularly in the context of national demographic data. Novel strategies should be pursued to supplement existing efforts to increase diversity in otolaryngology.

High prevalence of norovirus GII.4 Sydney among children with acute gastroenteritis in Bangladesh, 2018-2021.

BACKGROUND: Active molecular surveillance and rapid diagnosis method to track an outbreak of norovirus in Bangladesh is lacking. This study aims to determine the genotypic diversity, molecular epidemiology and evaluate a rapid diagnosis method. METHODS: A total of 404 fecal specimens were collected from children aged below 60 months from January 2018 to December 2021. All samples were analyzed by reverse transcriptase polymerase chain reaction molecular sequencing of partial VP1 nucleotide. Immunochromatography kit (IC, IP Rota/Noro) was evaluated against reference test method. RESULTS: We found norovirus in 6.7 % (27 of 404) fecal specimens. A wide diversity of norovirus genotype including GII.3, GII.4, GII.5, GII.6, GII.7, and GII.9 were detected. Norovirus strain GII.4 Sydney-2012 was the most predominant (74 %, 20 of 27) followed by GII.7 (7.4 %), GII.9 (7.4 %), GII.3 (3.7 %), GII.5 (3.7 %) and GII.6 (3.7 %), respectively. Co-infection of rotavirus and norovirus (19 [4.7 %] of 404) was the most prevalent. We found higher odds of prolonged health impact [OR 1.93 (95 % CI 0.87-3.12) (p = .001)] among patients with co-infection. The incidence of norovirus was significant among the children below 24 months (p = 0.001). Significant relation of temperature with the cases of norovirus was detected (p = 0.001). The IC kit provided high specificity (99.3 %) and sensitivity (100 %) for the detection of norovirus. CONCLUSIONS: This study will provide an integrated insight on the genotypic diversity and rapid identification method of norovirus in Bangladesh.