Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of Transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-SMA). The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension in a rat model. PAH was induced by a single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index and oxidative stress parameters were performed. Additionally, histopathology of lung and right ventricular of heart tissue, immunohistochemistry, expression of α-SMA, endothelial nitric oxide synthase (eNOS), TGF-ß, and RT-PCR, and an in vitro study using human umbilical vein endothelial cells (HUVECs) was also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress, and increase in expression of α-SMA and TGF-ß receptor 1 compared with MCT control group rats. In HUVECs, the expression of α-SMA was increased, whereas that of eNOS decreased after TGF-ß exposure and was substantially reversed after pretreatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the eNOS/TGF-ß/α-SMA signaling pathway.

Older PLHIV are at Higher Cardiovascular Risk with Poor Quality of Life.

BACKGROUND: People with HIV (PLHIV) face increased cardiovascular disease (CVD) risk due to inflammation and immune activation. Aging further amplifies this risk. Limited data exist on CVD risk in older PLHIV in India despite 2.14 million PLHIV with higher CVD risk factors. METHODS: In a cross-sectional study in Bihar, India, 73 PLHIV and 30 control participants were enrolled. Demographics, social factors, clinical information, and CVD risk factors were collected. HbA1c levels and lipid profiles were analyzed, and 10-year CVD risk scores were calculated using the Framingham risk score (FRS) and Qrisk3. Quality of life (QoL) was assessed using WHOQOL- HIV-BREF. RESULTS: Results showed higher LDL levels in non-HIV older participants and higher HDL levels in younger PLHIV participants. BMI differed significantly, with higher BMI in non-HIV older individuals and lower BMI in younger PLHIV individuals. Older PLHIV participants had significantly higher mean FRS and Q-Risk scores compared to older non-PLHIV and younger PLHIV groups. Among older PLHIV participants, six had higher CVD risk per FRS, while none in the other groups were classified as high CVD risk. Psychological, social relations and spirituality domains were highly deteriorated in older PLHIV, scoring 44.48, 42.72, and 41.2, respectively. The physical domain scored 57.6, and the environment scored 52.72 in the WHOQOL-HIV bref. CONCLUSION: In conclusion, older PLHIV in Bihar, India, face higher CVD risk compared to younger PLHIV and non-HIV individuals. FRS and Q-Risk scores effectively assessed CVD risk, identifying higher risk in older PLHIV. Age and BMI were significant predictors of high CVD risk. These findings emphasize CVD risk assessment and tailored management for older PLHIV. The QoL assessment findings indicate moderate deterioration in psychological, social relations, and spirituality domains among older PLHIV individuals. These results suggest greater challenges in psychological well-being, social interactions, and spirituality compared to the overall sample. Further research with larger samples and longitudinal designs is needed to confirm and extend these findings.

Barriers to the effective management and prevention of post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent.

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary.

Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy.

Despite little progress in survival rates with regular therapies, which do not provide complete care for curing pediatric brain tumors (PBTs), there is an urgent need for novel strategies to overcome the toxic effects of conventional therapies to treat PBTs. The co-inhibitory immune checkpoint molecules, e.g., CTLA-4, PD-1/PD-L1, etc., and epigenetic alterations in histone variants, e.g., H3K27me3 that help in immune evasion at tumor microenvironment have not gained much attention in PBTs treatment. However, key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, are greatly acknowledged. The crucial checkpoints in pediatric brain tumors are cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PDL1), OX-2 membrane glycoprotein (CD200), and indoleamine 2,3-dioxygenase (IDO). This review covers the state of knowledge on the role of multiple co-inhibitory immunological checkpoint proteins and histone epigenetic alterations in different cancers. We further discuss the processes behind these checkpoints, cell signalling, the current scenario of clinical and preclinical research and potential futuristic opportunities for immunotherapies in the treatment of pediatric brain tumors. Conclusively, this article further discusses the possibilities of these interventions to be used for better therapy options.

Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis.

BACKGROUND: Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant. METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively. RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one. CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia. PROSPERO: The registration number is CRD42022335233. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

Pharmacovigilance in the Caribbean Countries: an Overview.

Purpose of overview: The constant surge in accessing essential medicines creates a greater need for continuous monitoring of usage. The inability to source active pharmaceutical ingredients during the COVID-19 pandemic resulted in drug shortages that increased online requests for medications. E-commerce and social sites have opened the floodgate for the marketing of falsified, substandard, and unregistered pharmaceuticals, making them easily accessible to consumers with the click of a button. A high prevalence of such products with compromised quality highlights further the need for enhanced post-marketing vigilance of safety and quality within the pharmaceutical industry. This review aims to assess the extent to which pharmacovigilance (PV) systems in selected Caribbean countries conform to the minimum World Health Organization (WHO) requirements, highlight the importance of PV in ensuring the safer use of medicines across the Caribbean region, and identify opportunities and challenges in building comprehensive PV systems. Recent Findings: The review finds that while major advancements in PV and adverse drug reaction (ADR) monitoring have occurred in Europe and other parts of the Americas, little has been done in the Caribbean region. Only a few countries in the region are active members of the WHO's global PV network, and ADR reporting is minimal. The reason for low reporting includes a lack of awareness, commitment, and participation of healthcare professionals, manufacturers, authorized distributors, and the general consumers. Summary: Nearly all established national PV systems do not fully conform to the minimum PV requirements by the WHO. Legislation, regulatory framework, political commitment, adequate funding, strategies, and incentives to encourage reporting of ADRs are needed to build sustainable PV systems in the Caribbean.

The Use of Biomarkers in Pharmacovigilance: A Systematic Review of the Literature.

Background: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs). Objective: The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area. Design: This is a systematic review of the literature. Data Sources and Methods: Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance. Results: Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories. Conclusion: Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.

CD4 + Count: a Variable to Be Considered to Prioritize COVID-19 Vaccination in PLHIV.

The outbreak of the COVID-19 propagates, pressurizing the healthcare system by emphasizing and worsening the inequities. While many vaccines have shown excellent efficacy in protecting the general public from the COVID-19 infection, the efficacy of these vaccines for people living with HIV (PLHIV), especially those having a different range of CD4 + T-cell, has yet to be thoroughly investigated. Few studies have uncovered the escalated infection and death rates due to the COVID-19 infection in individuals with low CD4 + T-cells. Additionally, PLHIV has a low CD4 + count; furthermore, specific CD4 + T cells for coronavirus have a vigorous Th1 role and are related to the protective antibody responses. Follicular helper T cells (TFH) are vulnerable to HIV and virus-specific CD4 & CD8 T-cells which are essential for viral infection clearance and defective immune responses which further contributes to the development of illness. The specific CD8 & CD4 + T-cell reaction to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in almost all COVID-19 recovered individuals, which is related to the size of antibodies of immunoglobulin G. It has previously been demonstrated that PLHIV has decreased responses to certain vaccines and that these responses are reliant on CD4 + T-cell levels. COVID-19 vaccines will likely have a lower response or limited effect, in PLHIV having low CD4 + T-cells.

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis.

Leishmaniasis is a protozoal disease declared as an endemic in areas suffering from severe malnutrition and poverty. The factors associated with poverty like low income, ecological factors, and malnutrition cause disruption in immunity and host defense increasing risk of infection. Altered resistance to infection and host susceptibility are associated with low micronutrient levels in undernourished patients. Malnutrition has been recognized as a poor predictive marker for leishmaniasis, in particular the deficiency of trace elements like zinc, iron, and vitamin A, B, C, D which has a prominent function in the regulation of innate and adaptive immunity, cell proliferation, human physiology, etc. Malnourishment can exacerbate host sensitivity and pathophysiologic intensity to infection in variety of ways, whereas infection can enhance underlying poor nutrition or enhance host vulnerability and sandfly's urge to attack specific hosts. The intensity of leishmaniasis can be influenced by body mass and micronutrient availability in the blood. Vitamin D, C, zinc, and iron are proved effective in inhibiting the growth of leishmaniasis in both amastigote or promastigote forms, either directly or by acting as precursor for a pathway which inhibits the parasite growth. This article elucidates a new perception to the crucial role of micronutrients and their probable role in the therapeutic outcomes of leishmaniasis. Since there is requirement of novel drugs to fight drug resistance and relapse of leishmaniasis, this article may pave way to understand the importance of micronutrients and their role in therapeutic outcomes of leishmaniasis.

Assessing the Prevalence of Financial Toxicity, its Predictors and Association with Health- Related Quality of Life Among Radiation Oncology Patients in India: A Cross-Sectional Patient Reported Outcome Study.

PURPOSE: Financial toxicity has been associated with several clinical outcomes such as early mortality and poor quality of life. The aim of this study was to evaluate the magnitude of financial toxicity among radiation oncology patients and its association with health-related quality of life (HRQOL) in Indian health care settings. METHODS AND MATERIALS: This cross-sectional study was conducted among patients with cancer who had completed radiation therapy, either standalone or as part of a multimodal treatment. Financial toxicity and HRQOL were assessed using the Comprehensive Score for Financial Toxicity (COST) and Functional Assessment of Cancer Therapy: General (FACT-G) measures, respectively. Associations between financial toxicity and HRQOL were assessed using Pearson correlation. Univariate and multivariate regression analyses were conducted to identify the factors associated with financial toxicity. RESULTS: A total of 350 patients were included in this study. Of the 350 participants, 57.7% were male, 95.7% had no health insurance, and 61% were diagnosed with Head & Neck cancers. The average COST score was 15.38 ± 9.18 (range, 2-35), and the average FACT-G score was 69.63 ± 12.25 (range, 33-99). Based on the total COST score, 7.4% of participants reported grade 3 and 44.9% reported grade 2 financial toxicity. A significant positive correlation was observed between the COST and FACT-G scores, with a correlation coefficient of 0.58 (P < .001), indicating a large effect size. The COST score also significantly predicted the FACT-G score (ß = 0.77; 95% confidence interval [CI], 0.66-0.88; P < .001). The results of multivariate linear regression identified annual household income (ß = 3.9; 95% CI, 3.29-4.57; P < .001) and cancer type (ß = 3.74; 95% CI, 2.33-5.14; P < .001) as significant predictors of the COST score. CONCLUSIONS: More than 80% of the participants experienced financial toxicity in this study. The results highlight the need for interventions to alleviate the growing financial toxicity among cancer survivors in India.

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct.

Time trends in tuberculosis mortality across the BRICS: an age-period-cohort analysis for the GBD 2019.

Background: Tuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019. Methods: We obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Findings: There were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980. Interpretation: BRICS' actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country. Funding: National Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.

Knowledge, Attitude, and Practices among HIV/Leishmaniasis Co-Infected Patients in Bihar, India.

Visceral leishmaniasis (VL) is a serious public health concern in the Indian state of Bihar, which has been exacerbated by an increasing HIV/AIDS incidence that has resulted in poor clinical outcomes. So far, there has been no investigation into the knowledge, attitude, and practices (KAP) of people who have been subjected to hospital-based supervision for VL or HIV/VL co-infection. This study assessed the KAP toward VL infection among 210 VL-infected patients (126 participants with VL and 84 participants with HIV/VL) using a pretested standard questionnaire. The findings are summarized descriptively and KAP scores are classified dichotomously (good/poor). Multivariable logistic regression and bivariate correlation were used in the analysis. The study showed that both VL-infected and co-infected patients exhibited similar deficits in KAP scores toward VL. The HIV/VL participants who had a personal or family history of VL were more likely to have appropriate awareness of and preventive practices toward VL. The independent predictors of attitude index in HIV/VL participants were education, VL family history, and marital status. There was a weak but significant positive correlation between knowledge and practice (rs = 0.321, p<0.001), and attitude and practice (rs = 0.294, p<0.001), while knowledge was strongly correlated with attitude (rs = 0.634, p<0.001). Based on the study findings, it is recommended that treatment programs in Bihar should concentrate on strengthening KAP among VL and HIV/VL co-infected patients to prevent reinfection-related complications. Behavior change communication intervention is ideal for tackling this problem. This proposal entails building a comprehensive public health program in endemic regions.

Nutritional Aspects of People Living with HIV (PLHIV) Amidst COVID-19 Pandemic: an Insight.

Purpose of Review: This review elaborates the role of malnutrition in PLHIV (people living with HIV) in the context of COVID-19 and emphasis the need of supplementation, dietary intervention, and nutritional counselling in the post-COVID era. One of the most critical challenges among HIV/AIDS patients is malnutrition since it weakens the immune system and increases risk to opportunistic infections. In HIV (human immunodeficiency virus) infection, weight loss is prevalent due to reduced nutritional consumption, malabsorption, abnormal metabolism, and antiretroviral therapy. Sufficient nutrition is required for optimal immune function, as a result, food therapy is now considered an important adjuvant in the treatment of HIV patients. Recent Findings: Nutritional intervention, such as the use of dietary supplements, can help to prevent nutrient deficiency, lowering the death risk among malnourished HIV population. Immunocompromised individuals are at very high risk for COVID-19 and malnutrition increases the risk of infection by multiple folds. Interventions, such as nutrition education and counselling are important, to improve the condition of HIV Patients by optimising their nutritional status. Summary: A balanced diet should be one of the most important priorities in preventing PLHIV against the potentially deadly consequences of COVID-19. It is to be ensured that HIV-positive persons continue to get enough and appropriate assistance, such as nutrition and psychological counselling, in the context of COVID-19 infection. The use of telemedicine to maintain nutritional intervention can be beneficial. To meet their nutritional needs and minimise future difficulties, PLHIV infected with COVID-19 should get specialised nutritional education and counselling.

Impact of COVID-19 on Antimicrobial Resistance in Paediatric Population: a Narrative Review.

Purpose of Review: Irrational use of antimicrobials has been reported in paediatric population during the COVID-19 time period. This may lead to potential development of antimicrobial resistance and increased morbidity and mortality among this vulnerable population. The purpose of this review is to ascertain the impact of COVID-19 pandemic on antimicrobial resistance among paediatrics and the possible strategies to minimize the menace of antimicrobial resistance. Recent Findings: Recent findings indicate that the COVID-19 pandemic has direct as well as indirect impact on the development of antimicrobial resistance among paediatric population. Summary: This review article shows the impact of COVID-19 on the development of antimicrobial resistance and strategies to prevent it with special reference to antimicrobial stewardship programmes among paediatric population.

The Use of Artificial Intelligence in Pharmacovigilance: A Systematic Review of the Literature.

INTRODUCTION: Artificial intelligence through machine learning uses algorithms and prior learnings to make predictions. Recently, there has been interest to include more artificial intelligence in pharmacovigilance of products already in the market and pharmaceuticals in development. OBJECTIVE: The aim of this study was to identify and describe the uses of artificial intelligence in pharmacovigilance through a systematic literature review. METHODS: Embase and MEDLINE database searches were conducted for articles published from January 1, 2015 to July 9, 2021 using search terms such as 'pharmacovigilance,' 'patient safety,' 'artificial intelligence,' and 'machine learning' in the title or abstract. Scientific articles that contained information on the use of artificial intelligence in all modalities of patient safety or pharmacovigilance were reviewed and synthesized using a pre-specified data extraction template. Articles with incomplete information and letters to editor, notes, and commentaries were excluded. RESULTS: Sixty-six articles were identified for evaluation. Most relevant articles on artificial intelligence focused on machine learning, and it was used in patient safety in the identification of adverse drug events (ADEs) and adverse drug reactions (ADRs) (57.6%), processing safety reports (21.2%), extraction of drug-drug interactions (7.6%), identification of populations at high risk for drug toxicity or guidance for personalized care (7.6%), prediction of side effects (3.0%), simulation of clinical trials (1.5%), and integration of prediction uncertainties into diagnostic classifiers to increase patient safety (1.5%). Artificial intelligence has been used to identify safety signals through automated processes and training with machine learning models; however, the findings may not be generalizable given that there were different types of data included in each source. CONCLUSION: Artificial intelligence allows for the processing and analysis of large amounts of data and can be applied to various disease states. The automation and machine learning models can optimize pharmacovigilance processes and provide a more efficient way to analyze information relevant to safety, although more research is needed to identify if this optimization has an impact on the quality of safety analyses. It is expected that its use will increase in the near future, particularly with its role in the prediction of side effects and ADRs.

Nasal vaccine as a booster shot: a viable solution to restrict pandemic?

The coronavirus disease 2019 (COVID-19) pandemic revolutionized the vaccine market and initiated the momentum for alternative routes of administration for vaccines. The intranasal route of immunization is one such possibility that appears to be the most promising since it has some significant advantages, particularly in the prevention of respiratory infection. To analyze and summarize the role of nasal vaccines over conventional vaccines during COVID-19 and the need for the nasal vaccine as a booster shot. In this narrative review, the required data was retrieved using keywords "COVID-19," "Intranasal," "Immunity," "Nasal spray," and "Mucosal" in databases including PubMed, Scopus, Embase, Science Direct, and Web of Sciences. The results of the study showed that the nasal vaccines were both effective and protective according to the current researches approaching during the COVID-19 period and the preclinical and clinical phase trials prove the intranasal vaccination elicits more robust and cross-protective immunity than conventional vaccines. In this narrative review article, mechanisms across the nasal mucosa will be briefly presented and the current status of nasal vaccines during the COVID-19 pandemic is summarized, and advantages over traditional vaccines are provided. Furthermore, after exploring the primary benefits and kinetics of nasal vaccine, the potential for consideration of nasal vaccine as a booster dose is also discussed.

Efficacy and safety of vitamin D in tuberculosis patients: a systematic review and meta-analysis.

BACKGROUND: Evidence from the basic research and epidemiological studies indicates a beneficial effect of vitamin D in the treatment of tuberculosis (TB). However, the evidence from randomized controlled trials (RCTs) is inconsistent. OBJECTIVES: This systematic review and meta-analysis was performed to synthesize evidence regarding role of vitamin D versus placebo for the management of TB. MATERIALS AND METHODS: We searched PubMed and Cochrane Clinical Trial Registry for RCTs comparing vitamin D versus placebo for the treatment of TB. RCTs enrolling adult patients with TB receiving vitamin D in addition to standard treatment were included. Data were pooled using random effects model. The study was conducted according to PRISMA guidelines and protocol was registered with PROSPERO (CRD42016052841). RESULTS: Of 605 identified references, 12 RCTs were included. The overall risk of bias in included studies was low or unclear. There was no significant difference between vitamin D and placebo group for any outcomes of efficacy (time to culture conversion, time to smear conversion, rate of culture conversion, and rate of smear conversion) or safety (mortality, serious adverse events, and nonserious adverse events). CONCLUSION: Vitamin D administered with standard treatment has no beneficial effect in the TB patients as compared to the placebo.

Targeting Specific Checkpoints in the Management of SARS-CoV-2 Induced Cytokine Storm.

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.

Arsenic: a Culpable Element and a Possible Menace for HIV/AIDS Patients.

Arsenic contamination has long been recognized as one of the most harmful environmental pollutants resulting from anthropogenic activity. Apart from being an environmental toxicant or pollutant, this culpable heavy metal also has detrimental effects on human health. People throughout the world are exposed to arsenic (As) mostly through polluted drinking water. Acute inorganic arsenic (iAs) poisoning causes nausea, vomiting, stomach discomfort, and severe diarrhea. As on long-term exposure is a potent carcinogen, characterized by IARC (International Agency for Research on Cancer). As levels are high mainly in Gangetic regions due to which the people living around are suffering the consequences. The carcinogenicity of As is well established but the immunotoxicity caused by it is still unknown. Some animal model supports the toxicity of As in the immune system as well, but in humans, mainly suffering from human immunodeficiency virus (HIV), it is not well established. iAs suppresses the immune system by acting on different targets and exacerbating infections. Although animal studies have demonstrated that arsenic trioxide (As2O3) reduces viral rebound and restores CD4 + count in vivo when coupled with antiretroviral medications, elemental AS may have devastating effects on the immune system of HIV patients, making them more prone to opportunistic infections (OIs). It is well known that in later stages of HIV infection, neurological problems also complicate the conditions such as cognitive impairment and AIDS dementia complex (ADC). Along with immunotoxicity, As has the potential to damage HIV patients' brains. This article addresses the immunotoxicity of arsenic and exacerbations caused by it, along with the neurotoxicity, particularly in HIV patients residing near the Gangetic belt.