Comparative analysis of plasma affinity depletion methods: Impact on protein composition and phosphopeptide abundance in human plasma.

Affinity-based protein depletion and TiO2 enrichment methods play a crucial role in detection of low-abundant proteins and phosphopeptides enrichment, respectively. Here, we assessed the effectiveness of HSA/IgG (HU2) and Human 7 (HU7) depletion methods and their impact on phosphopeptides coverage through comparative proteome analysis, utilizing in-solution digestion and nano-LC-Orbitrap mass spectrometry (MS). Our results demonstrated that both HU2 and HU7 affinity depletion significantly decreased high-abundant proteins by 1.5-7.8-fold (p < 0.001). A total of 1491 proteins were identified, with 48 proteins showing significant expression in the depleted groups. Notably, cadherin-13, neutrophil defensin 1, APM1, and desmoplakin variant protein were exclusively detected in the HU2/HU7-depleted groups. Furthermore, study on effect of depletion on phosphopeptides revealed an increase in tandem MS spectral counts with notable decrease (∼50%) in peptide spectrum matching in depleted groups, which was attributed to significant reduction in protein counts. Our post translation modification workflow for phosphoproteomics detected 42 phosphorylated peptides, corresponding to 12 phosphoproteins with unique peptide match ≥2 (high false discovery rates confidence). Among them, 10 phosphorylated proteins are highly expressed in depleted groups. Overall, these findings offer valuable insights in selection of protein depletion methods for comprehensive plasma proteomics analysis.

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.

Investigation of antimicrobial susceptibility patterns, risk factors and their impact on mortality in cancer patients at a tertiary care cancer hospital- A prospective study.

BACKGROUND: Cancer patients are vulnerable to infections due to immunosuppression caused by cancer itself and its treatment. The emergence of antimicrobial-resistant bacteria further complicates the treatment of infections and increases the mortality and hospital stays. This study aimed to investigate the microbial spectrum, antimicrobial resistance patterns, risk factors, and their impact on clinical outcomes in these patients. METHODS: A prospective study was conducted at a tertiary care cancer hospital in Patna, Bihar, India, which included cancer patients aged 18 years and older with positive microbial cultures. RESULTS: This study analysed 440 patients, 53% (234) of whom were females, with an average age of 49.27 (± 14.73) years. A total of 541 isolates were identified, among which 48.01% (242) were multidrug resistant (MDR), 29.76% (150) were extensively drug resistant (XDR), and 19.84% (112) were sensitive. This study revealed that patients who underwent surgery, chemotherapy, were hospitalized, had a history of antibiotic exposure, and had severe neutropenia were more susceptible to MDR and XDR infections. The average hospital stays were 16.90 (± 10.23), 18.30 (± 11.14), and 22.83 (± 13.22) days for patients with sensitive, MDR, and XDR infections, respectively. The study also revealed overall 30-day mortality rate of 31.81% (140), whereas the MDR and XDR group exhibited 38.92% and 50.29% rates of 30-day mortality respectively (P < 0.001). Possible risk factors identified that could lead to mortality, were cancer recurrence, sepsis, chemotherapy, indwelling invasive devices such as foley catheter, Central venous catheter and ryles tube, MASCC score (< 21) and pneumonia. CONCLUSIONS: This study emphasizes the necessity for personalized interventions among cancer patients, such as identifying patients at risk of infection, judicious antibiotic use, infection control measures, and the implementation of antimicrobial stewardship programs to reduce the rate of antimicrobial-resistant infection and associated mortality and hospital length of stay.

Ophthalmic adverse effects of miltefosine in the treatment of leishmaniasis: a systematic review.

OBJECTIVE: Miltefosine stands as the sole oral medication approved for the treatment of leishmaniasis. The appearance of severe ophthalmic toxicities induced by miltefosine in the context of leishmaniasis treatment is a matter of significant concern. The main objective of this study is to present a comprehensive summary of the ophthalmic adverse effects associated with miltefosine when used in the treatment of leishmaniasis. METHODS: A systematic search was performed on PubMed, ScienceDirect, Embase, Scopus, and Google Scholar, covering articles from inception up to June 2023, without language restrictions, to identify relevant studies documenting ocular toxicity following miltefosine treatment for leishmaniasis. RESULTS: A total of eight studies involving 31 leishmaniasis patients who developed ocular toxicities while undergoing miltefosine treatment were included in the analysis. These studies were conducted in various regions, with five originating from India, two from Bangladesh, and one from Nepal. Patients presented a spectrum of ophthalmic complications, including uveitis, keratitis, scleritis, and Mooren's ulcer. Commonly reported symptoms included pain, redness, excessive tearing, partial vision impairment, permanent blindness, light sensitivity, and the appearance of white spots on the eye. On average, patients received miltefosine treatment for a duration of 47 days before experiencing the onset of ocular problems. It is important to note that the risk of ocular toxicities increases with prolonged use of miltefosine. CONCLUSIONS: Therefore, to mitigate the potential for irreversible damage to the eyes, it is imperative that all individuals undergoing miltefosine therapy undergo regular eye examinations.

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.

Adverse Events Reported From COVID-19 Vaccine Trials: A Systematic Review.

COVID-19 infection originated in Wuhan, China in December 2019 and crippled human health globally in no time. The public health emergency required urgent efforts to develop and test the efficacy and safety of vaccines to combat the COVID-19 pandemic. The emergency use approval has been granted to COVID-19 vaccines before the completion of conventional phases of clinical trials. However, there is no comprehensive review of safety data reported from the vaccine trials, which is critical information to inform the policies in order to improve uptake of COVID-19 vaccines and mitigate the risk aversion perceived due to the COVID-vaccine side effects. This study aims to systematically review and synthesize the evidence on the safety data from the published COVID-19 vaccine trials. This study followed PRISMA guidelines. We searched three major electronic databases (PubMed, Embase, and Google Scholar) for published studies between Dec 2019 and 2020. Eligible study designs were randomized trials and pre-and post-intervention evaluations. Descriptive findings of included studies were reported stratified by target population, setting, outcomes, and overall results. From PubMed, Embase, WHO database, and Google Scholar screened titles and abstracts, 11 studies were identified in this review. Most of the reactions reported were mild to moderate whereas a few with severe intensity. All reactions resolved within 3-4 days. The commonly reported local adverse events were pain at the site of injection, swelling, and redness. The systemic reactions included fever, fatigue, myalgia, and headache. Some trials also reported laboratory derangements  like decreased hemoglobin, increased bilirubin, altered SGOT and SGPT. None of these alterations were clinically manifested and were self-limiting. Few clinical trials reported serious adverse events, but they were unrelated to vaccination. This systematic review indicates that COVID-19 vaccines can be safe with no serious adverse events. However, long-term post-marketing surveillance data, particularly in high-risk vulnerable populations (elderly and those with co-morbidities, pregnant women, and children) is warranted to ensure the safety of COVID-19 vaccines.

Targeting oxidative stress, acetylcholinesterase, proinflammatory cytokine, dopamine and GABA by eucalyptus oil (Eucalyptus globulus) to alleviate ketamine-induced psychosis in rats.

Essential oil of eucalyptus species is among the most common traded essential oils in the world. There is an increasing interest in the application of eucalyptus oil as a natural additive in food and pharmaceutical industry. The present study was undertaken to identify the phytoconstituents present in the essential oil of Eucalyptus globulus leaves (EO) and ascertain their protective effect against ketamine-induced psychosis in rats. GC-MS technique was used for analysis of phytoconstituents present in EO. Ketamine (50 mg/kg, i.p.) was used to induce psychosis in rats. Photoactometer, forced swim test and pole climb avoidance test were used to evaluate the protective effects of the EO (500, 1000 and 2000 mg/kg, p.o.) on acute and chronic administration. Bar test was used to test the side effect of EO. Biochemical and neurochemical estimations were carried out to explore the possible mechanism of action. GC-MS analysis of EO showed the presence of a number of biologically active compounds. EO at the dose of 500, 1000 and 2000 mg/kg, p.o. on acute and chronic administration, decreased locomotor activity, immobility duration and latency to climb the pole. EO was effective to facilitate the release of GABA, increase GSH levels, inhibit dopamine neurotransmission and decrease TNF-α levels as well as diminish AChE activity in different regions of the brain. EO at the dose of 500, 1000 mg/kg did not produce cataleptic behavior in rats. EO at the dose of 500, 1000 mg/kg produced protective effects against ketamine-induced psychosis and can be further explored clinically against neuropsychiatric disorders.

Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

Potential drug targets and treatment of schizophrenia.

Schizophrenia is one of the most prevalent chronic psychiatric disorders that affect 1% of the world's population. Despite its societal burden, pathophysiology of schizophrenia remains poorly understood. Currently available drugs predominantly control positive symptoms, and often have no or poor control on negative and related cognitive symptoms, which strongly affect functional outcome in schizophrenia. The present article is an attempt to provide a critical review of recent hypothesis to understand pathophysiology of schizophrenia and to highlight exploitable molecular drug targets other than dopaminergic systems to treat and manage schizophrenia effectively.

Hepatoprotective effect of trimethylgallic acid esters against carbon tetrachloride-induced liver injury in rats.

Gallic acid and its derivatives are potential therapeutic agents for treating various oxidative stress mediated disorders. In the present study, we investigated the hepatoprotective effects of newly synthesized conjugated trimethylgallic acid (TMGA) esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Animals were pre-treated with TMGA esters at their respective doses for 7 days against CCl4-induced hepatotoxicity. The histopathological changes were evaluated to find out degenerative fatty changes including vacuole formation, inflammation and tissue necrosis. Various biomarkers of oxidative stress (lipid peroxidation, glutathione levels, and endogenous antioxidant enzyme activities), liver enzymes (AST and ALT), triacylglycerol and cholesterol were evaluated. Pre-treatment with TMGA esters (MRG, MGG, MSG, and MUG at the dose of 28.71, 30.03, 31.35, 33.62 mg/kg/day), respectively reversed the CCl4-induced liver injury scores (reduced vacuole formation, inflammation and necrosis), biochemical parameters of plasma (increased AST, ALT, TG, and cholesterol), antioxidant enzymes (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities) in liver tissues and inflammatory surge (serum TNF-α) significantly. The study revealed that TMGA esters exerted hepatoprotective effects in CCl4-induced rats, specifically by modulating oxidative-nitrosative stress and inflammation.

Psychological health among healthcare professionals during COVID-19 pandemic: An updated meta-analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic outbreak created a challenge to manage the health, especially the mental health of various care providers involved in treating the patients infected with the virus. Previously published literature has shown a significant effect of the pandemic on the psychological health of healthcare workers (HCWs) globally; so, this study aimed to describe the psychological health outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Indian HCWs. Methods: An extensive literature search was conducted in databases including PubMed and Google Scholar. The search was restricted from the COVID-19 outbreak until June 2022. Cross-sectional studies and other studies (telephonic interviews and survey-based studies) reported the prevalence of anxiety and depression among frontline HCWs since the onset of the COVID-19 pandemic. All the studies were critically evaluated by two individual authors in terms of screening and methodological quality evaluation. A total of 16 studies were included in the final meta-analysis. Results: The prevalence of depression among n = 12231 participants of 14 studies was 0.37 CI 95% [0.28-0.48]; the prevalence of anxiety among n = 9467 participants of 12 studies was 0.39 CI 95% [0.29-0.49]. The results of the overall meta-analysis indicate that 37% and 39% of HCWs in this study experienced mild-to-severe depression and anxiety, respectively. During the COVID-19 pandemic, a significant number of HCWs developed mental health issues, with a reported prevalence of depression (37%) and anxiety (39%). Conclusion: Frontline HCWs' mental health should get full consideration during public health emergencies, screening should be actively conducted, and specific steps should be taken to lower the fear associated with the risk of infections.

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).

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.

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.

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.

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.

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.

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.

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.