Cardiovascular positron emission tomography: established and emerging role in cardiovascular diseases.

Cardiac positron emission tomography (PET) imaging has established themselves firmly as excellent and reliable functional imaging modalities in assessment of the spectrum of coronary artery disease. With the explosion of technology advances and the dream of flow quantification now a reality, the value of PET is now well realized. Cardiac PET has proved itself as precise imaging modality that provides functional imaging of the heart in addition to anatomical imaging. It has established itself as one of the best available techniques for evaluation of myocardial viability. Hybrid PET/computed tomography provides simultaneous integration of coronary anatomy and function with myocardial perfusion and metabolism, thereby improving characterization of the dysfunctional area and chronic coronary artery disease. The availability of quantitative myocardial blood flow evaluation with PET provides additional prognostic information and increases diagnostic accuracy in the management of patients with coronary artery disease. Hybrid imaging seems to hold immense potential in optimizing management of cardiovascular diseases and furthering clinical research.

SARS-CoV-2-Specific Neutralizing Antibody Responses in Norwegian Health Care Workers After the First Wave of COVID-19 Pandemic: A Prospective Cohort Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in health care workers (HCW) due to overburdened health care systems. Whether infected HCW acquire protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. METHODS: In a Norwegian prospective cohort study, we enrolled 607 HCW before and after the first COVID-19 wave. Exposure history, COVID-19-like symptoms, and serum samples were collected. SARS-CoV-2-specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. RESULTS: Spike-specific IgG/IgM/IgA antibodies increased after the first wave in HCW with, but not in HCW without, COVID-19 patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse transcriptase polymerase chain reaction (RT-PCR) during follow-up; 8 were positive (7 seroconverted, 1 had undetectable antibodies). CONCLUSIONS: We found increases in SARS-CoV-2 neutralizing antibodies in infected HCW, especially after COVID-19 patient exposure. Our data show a low number of SARS-CoV-2-seropositive HCW in a low-prevalence setting; however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing.

Comparative analysis of outcomes and long-term follow-up of robot-assisted pediatric kidney transplantation, with open counterpart.

How does the robotic kidney transplant fare against the open technique, in pediatric patients? No one knows. To address this question, this study compares the outcomes of robotic kidney transplants, with those of open transplant in these patients. This study was a retrospective analysis of outcomes (renal function and complications), of all pediatric patients (<18 years of age), who underwent kidney transplant at our institute, after 2014, till their last follow-up. Fisher's exact test was used to compare proportions. Continuous variables were analyzed using Mann-Whitney test. P value of <.05 was considered significant. Of the twenty-five patients included, 21 belonged to open group, and 4 to the robotic group. Patients in the robotic group had significantly higher Re-WIT (P value .002) and had lower analgesia requirement (P value .04). Median follow-up period was 31 months. Both groups were comparable in terms of length of hospital stay, blood transfusion, and renal function post-operatively till their last follow-up. Three patients in the open group had surgical site infection as compared to none in the robotic group. All the patients had functioning grafts till their last follow-up. Robotic transplant is safe and delivers functional results similar to open technique, with lesser pain and better cosmesis. Longer Re-WIT in robotic transplant has no impact on post-operative renal function. Ours is the first known effort to compare robotic technology with the established open technique of transplant in this population. A prospective randomized controlled trial should refine the results of the present study.

Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.

Evaluation of an adjuvanted hydrogel-based pDNA nanoparticulate vaccine for rabies prevention and immunocontraception.

Immunocontraceptive vaccination is becoming an acceptable strategy in managing animal populations. Mass vaccination of dogs is the most cost-effective and efficient method to control rabies, and combination of rabies vaccination and animal population control will be an added advantage. In this study, we developed an adjuvanted hydrogel-based pDNA nanoparticulate vaccine for rabies protection and immunocontraception. In vivo, we observed an immune response skewed toward a Th2 type, in contrast to the Th1 type in our previous pDNA study. The observation was verified by the IgG2a/IgG1 ratio (<1), and cytokine expression profile of IL-4 and IFN-γ. The humoral immune response is key for rabies protection and a GnRH antibody-based immunocontraception. In mice, anti-GnRH antibody titers were detected 4 weeks after immunization and lasted for 12 weeks, post animal experiment was terminated. The adjuvanted pDNA nanoparticulate vaccine shows promise for future studies evaluating protection from rabies challenge and prevention of animal breeding.

Outcome and predictors of cardiopulmonary resuscitation among patients admitted in Medical Intensive Care Unit in North India.

BACKGROUND: Outcome and predictors of survival after cardiopulmonary resuscitation (CPR) in Intensive Care Units (ICUs) have been extensively studied in western world, but data from developing countries is sparse. OBJECTIVES: To study the outcome and predictors of survival after CPR in a Medical ICU (MICU) of a tertiary level teaching hospital in North India. MATERIALS AND METHODS: A 1-year prospective cohort study. RESULTS: Of 105 in-MICU CPRs, forty patients (38.1%) achieved return of spontaneous circulation (ROSC). Only one patient (0.9%) survived up to hospital discharge. The predictors of ROSC were ventricular tachycardia/ventricular fibrillation as first monitored rhythm, intubation during CPR and CPR duration ≤ 10 min. CPR duration > 10 min was a significant factor for resuscitation failure. CONCLUSIONS: The rate of survival to hospital discharge after in-MICU CPRs is extremely poor. Our data may aid treating physicians, resuscitation teams, and families in understanding the likely outcome of patients after in-MICU CPRs.

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems.

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract.

Outcomes in transcatheter aortic valve replacement (TAVR) patients requiring red blood cell transfusion: A nationwide perspective.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) can be complicated by anemia due to periprocedural bleeding, hemolysis, vascular events, or significant bleeding associated with antiplatelet therapy. OBJECTIVE: We used the National Inpatient Sample (NIS) database to study the outcomes of patients who underwent TAVR and developed significant anemia requiring red blood cell (RBC) transfusion. METHODS: This is a retrospective cohort study utilizing the NIS database from 2016 to 2017. We identified patients who underwent TAVR and required RBC transfusion using ICD-10 and PCS-10 codes. The primary outcome was all-cause inpatient mortality, and the secondary outcomes were the cost of hospitalization and length of stay (LOS). Student t-test, Chi-square, and ANOVA were utilized for statistical analysis where applicable. Multivariate logistic regression was used to adjust for potential confounders. STATA 15.0 was utilized for data analysis. RESULTS: A total of 18,325 patients underwent TAVR in 2016-2017. Among them, 6.7 % of patients required RBC transfusion. Patients were relatively older in the transfusion group (81 yrs vs 79 yrs; p < 0.001). The mean cost of hospitalization was higher in the transfusion group (283,153 USD vs 208,939 USD; p < 0.001). The mean length of stay (LOS) was higher in the transfusion group (9.0 days vs 4.3 days; p < 0.001). Patients in the transfusion group had higher inpatient all-cause mortality compared to patients without transfusion (6.1 % vs 1.3 %; odds ratio 4.94; p < 0.001, 95 % CI 3.7-6.4). Inpatient mortality and LOS didn't differ by race or sex in the transfusion group. All-cause mortality, LOS, and cost of hospitalization were independently increased by transfusion after adjusting for potential confounders i.e. sex, race, hospital teaching status, hospital region, heart block, pacemaker, arrhythmias, heart failure, diabetes, pulmonary hypertension, CKD, and others using multivariate logistic regression. CONCLUSION: In patients undergoing TAVR, blood transfusion was associated with adverse outcomes including increased mortality, length of stay, and cost of hospitalization. The role of careful patient selection, judicious use of antiplatelets, anticoagulants, and pre-procedural optimization of anemia needs further investigation to optimize patient outcomes.

Spontaneous coronary artery dissection (SCAD) and takotsubo cardiomyopathy (TCM) - A potential association.

Background: Spontaneous coronary artery dissection and takotsubo cardiomyopathy are increasingly recognized in the last two decades. Case reports have shown both entities can present concomitantly - however, little is known about their association. Methods: In this retrospective study we aimed to explore a potential association between SCAD and TCM using the Nationwide Inpatient Sample. The odds of having TCM among patients with SCAD compared with those who did not have SCAD were calculated as an odds ratio. Conversely, the odds of having SCAD among patients with TCM compared with those who did not have TCM were also calculated. The primary outcome was the odds of TCM among patients with a primary diagnosis of SCAD and vice versa. The secondary endpoint was the odds of in-hospital mortality among patients with SCAD, and/or TCM. Results: Hospitalized patients who had SCAD were 7.12 (95 % CI: 6.28-8.08) times more likely to also have TCM than those who did not have SCAD (p < 0.0001).), while patients with TCM were 6.91 (95 % CI: 6.07-7.85) times more likely to have SCAD compared to those who didn't have TCM adjusted for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus (p < 0.0001). Conclusion: This data indicate that patients with either SCAD or TCM are seven times more likely to be diagnosed concomitantly with both, compared to the patients without either diagnosis [after adjusting for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus]. Our data are consistent with the growing body of evidence supporting an association between SCAD and TCM and raise the question of a common pathophysiologic mechanism.

From rejection to the Nobel Prize: Karikó and Weissman's pioneering work on mRNA vaccines, and the need for diversity and inclusion in translational immunology.

Katalin Karikó and Drew Weissman were given the 2023 Nobel Prize in Physiology or Medicine for their findings of nucleoside base modifications that lead to the development of effective mRNA vaccines against COVID-19. This was a remarkable achievement, given that their initial manuscript was rejected by Nature and Science in 2005. The development of mRNA vaccines lagged for more than a decade for several reasons, including the lack of funding, the perceived risks of the technology, and the scepticism of many scientists. Furthermore, Karikó and Weissman's study appeared to be technical and difficult to understand. The COVID-19 pandemic, on the other hand, has shown the importance of mRNA vaccine technology. COVID-19 mRNA vaccines have been highly effective in preventing serious illness, hospitalization, and death. The Nobel Prize for Karikó and Weissman highlights the importance of perseverance, diversity, and inclusion in translational immunology. We need to build a more inclusive scientific community, where scientists from all backgrounds are supported and their work is valued. This will result in more scientific breakthroughs and better healthcare for everyone.

A Comparison of the Quality of Life of People With Epilepsy Receiving Home-Based and Clinic-Based Epilepsy Care Using the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) Scale.

Background and objective Epilepsy is a chronic neurological condition that, both physically and psychologically, puts a person at risk for poor quality of life (QOL). People with epilepsy (PWE) may experience shame, fear, and rejection and feel discriminated against, hence avoiding social interactions. To avoid being labeled as having epilepsy, patients may conceal their disease and refuse medical attention, which can lead to treatment discontinuation and significantly impact the quality of life. Epilepsy care in India has fallen back on primary care physicians because there are not enough neurologists available to treat the condition. Home-based care (HBC) may overcome many barriers by providing free antiepileptic drugs (AEDs), eliminating the "distance to a health facility," and providing correct information that may improve QOL. This study is therefore conducted to compare the QOL between people with epilepsy receiving home-based care (HBC) and routine clinic-based care (CBC). Methodology The people with epilepsy enrolled in this study were already part of a community-based randomized controlled trial conducted to compare the effect of regular home-based epilepsy care with routine clinic-based epilepsy care on antiepileptic adherence among urban and peri-urban areas of Ludhiana, Punjab, India (explained further in the study). The present study is a cohort study where the two cohorts, one receiving home-based epilepsy care (n = 97) and the other receiving routine clinic-based epilepsy care (n = 76), were compared for QOL at two points in time, i.e., at baseline (at enrolment) and after 24 months of receiving epilepsy care, using the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) scale. Results The mean EQ-5D-3L index scores for the HBC group at baseline were 0.88 ± 0.15, and after 24 months, the scores increased to 0.94 ± 0.17. The baseline mean index scores for the CBC group were 0.89 ± 0.21, and after 24 months, the value increased to 0.90 ± 0.19. The mean difference in QOL in the HBC group showed a higher difference than in the CBC group (0.06 ± 0.1 versus 0.01 ± 0.1), but the difference was found to be statistically not significant (p = 0.067). As per the five dimensions of the EQ-5D-3L scale, i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, there was a decrease in the number of PWE reporting problems among both groups after 24 months of epilepsy care. Sociodemographic and clinical variables such as level of education, working status, age at the onset of seizures, frequency of seizures, treatment regimen, presence of comorbidities, and adverse drug reactions significantly affect the QOL of people with epilepsy at p < 0.05. Conclusion The results of the study emphasize that epilepsy has a negative impact on QOL. The results showed a higher QOL among the people in the HBC group as compared to the CBC group, but the difference was not statistically significant. There was an improvement in QOL from baseline after dedicated care in both groups. The problems related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression have been significantly reduced in the HBC group. Having low levels of education, not having a job, starting to have seizures at a young age, having seizures more often, receiving more than one type of treatment, and the presence of other health problems and side effects are factors associated with poor QOL among people with epilepsy.

Progress in drug delivery and diagnostic applications of carbon dots: a systematic review.

Carbon dots (CDs), which have particle size of less than 10 nm, are carbon-based nanomaterials that are used in a wide range of applications in the area of novel drug delivery in cancer, ocular diseases, infectious diseases, and brain disorders. CDs are biocompatible, eco-friendly, easy to synthesize, and less toxic with excellent chemical inertness, which makes them very good nanocarrier system to deliver multi-functional drugs effectively. A huge number of researchers worldwide are working on CDs-based drug delivery systems to evaluate their versatility and efficacy in the field of pharmaceuticals. As a result, there is a tremendous increase in our understanding of the physicochemical properties, diagnostic and drug delivery aspects of CDs, which consequently has led us to design and develop CDs-based theranostic system for the treatment of multiple disorders. In this review, we aim to summarize the advances in application of CDs as nanocarrier including gene delivery, vaccine delivery and antiviral delivery, that has been carried out in the last 5 years.

Indicators of Self-Determination in Therapeutic Songwriting Lyrics Created by Adults with High LDL Cholesterol.

Individuals with low-density lipoprotein cholesterol ≥190 mg/dL are at high risk for atherosclerotic cardiovascular disease events. Our goal was to determine if adults with this condition would express important psychological, health, and motivation themes when generating lyrics during music therapy. Thirty-one participants each created their own original song with the help of a music therapist. The lyrics were analyzed using a deductive approach guided by Self-Determination Theory (specifically the satisfaction or frustration of basic psychological needs): (1) for each entire song (macro-analysis) and (2) line-by-line (micro-analysis). Song lyrics generated during music therapy sessions by patients with a low-density lipoprotein cholesterol ≥190 mg/dL revealed the presence of the three basic needs (autonomy, competence, and relatedness) of Self-Determination Theory. The most prevalent theme identified in the macro-analysis of songs was autonomy satisfaction, coded in 25 songs (27.17% of all macro codes), and followed by competence satisfaction in 17 songs (18.48%) and relatedness satisfaction in 15 songs (16.3%). Line-by-line micro-analysis of lyrics revealed that at least one basic need of Self-Determination Theory was present in 277 of the unique lyric lines (50%); 107 (19%) for relatedness, 101 (18%) for autonomy, and 69 (13%) for competence. Need satisfaction occurred more frequently than need frustration in both analyses. However, depending on the level of analysis (macro or micro), results differed as to which themes were most prevalent. These results indicate that therapeutic songwriting may be a unique way to identify the basic psychological needs that, when satisfied, indicate self-determination.

Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis.

Cryptogenic stroke (CS) accounts for approximately 25% of ischemic stroke cases, with atrial fibrillation (AF) accounting for 30% of CS cases. We investigated the utility of left atrial (LA) speckle-tracking echocardiography in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long-term rhythm monitoring devices. Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF vs no AF.  We used the inverse variance method with the DerSimonian-Laird estimator for tau2 and Hartung-Knapp adjustment for random effect analysis. I2 was used to assess heterogeneity. Thirteen observational studies met our criteria and included 3031 patients with new CS. Of those, 420 patients developed AF on follow-up, and 2611 patients did not develop AF. The AF group vs. no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.61; 95% CI: -10.76, -6.47, I2 = 85%, p < 0.01] at presentation. LARS is significantly lower in patients who developed AF after CS. More studies are needed to validate this data.

Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers.

Background: Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. Methods: From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021. Results: We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8-12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5-17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5-35.1) and occupational exposure (OR 2.2; 95% CI: 1.4-3.2). Conclusion: We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults.

Objectives: Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Methods: Home-dwelling old (n = 100, median 86 years) and younger adults (n = 449, median 38 years) were vaccinated with two doses of BNT162b2 vaccine at 3-week intervals and followed for 9-months. Vaccine-induced responses were compared to home-isolated COVID-19 patients (n = 183, median 47 years). Our analysis included neutralizing antibodies, spike-specific IgG, memory B-cells, IFN-γ and IL-2 secreting T-cells and sequencing of the T-cell receptor (TCR) repertoire. Results: Spike-specific breadth and depth of the CD4+ and CD8+ TCR repertoires were significantly lower in the elderly after one and two vaccinations. Both vaccinations boosted IFN-γ and IL-2 secreting spike-specific T-cells responses, with 96 % of the elderly and 100 % of the younger adults responding after the second dose, although responses were not maintained at 9-months. In contrast, T-cell responses persisted up to 12-months in infected patients. Spike-specific memory B-cells were induced after the first dose in 87 % of the younger adults compared to 38 % of the elderly, which increased to 83 % after the second dose. Memory B-cells were maintained at 9-months post-vaccination in both vaccination groups. Neutralizing antibody titers were estimated to last for 1-year in younger adults but only 6-months in the older vaccinees. Interestingly, infected older patients (n = 15, median 75 years) had more durable neutralizing titers estimated to last 14-months, 8-months longer than the older vaccinees. Conclusions: Vaccine-induced spike-specific IgG and neutralizing antibodies were consistently lower in the older than younger vaccinees. Overall, our data provide valuable insights into the kinetics of the humoral and cellular immune response in the elderly after SARS-CoV-2 vaccination or infection, highlighting the need for two doses, which can guide future vaccine design.Clinical trials.gov; NCT04706390.

Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries.

PURPOSE: In low- and middle-income countries (LMICs), a large proportion of people with epilepsy do not receive treatment. An analysis of the availability, price, and affordability of antiepileptic drugs (AEDs) was conducted to evaluate whether these factors contribute to the treatment gap. METHODS: Data for five AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, and diazepam) were obtained from facility-based surveys conducted in 46 countries using the World Health Organization/Health Action International (WHO/HAI) methodology. Outcome measures were percentage availability, ratios of local prices to international reference prices, and number of days' wages needed by the lowest-paid unskilled government worker to purchase treatment. Prices were adjusted for inflation/deflation and purchasing power parity. KEY FINDINGS: The average availability of generic AEDs in the public sector was <50% for all medicines except diazepam injection. Private sector availability of generic oral AEDs ranged from 42.2% for phenytoin to 69.6% for phenobarbital. Public sector patient prices for generic carbamazepine and phenytoin were 4.95 and 17.50 times higher than international reference prices, respectively, whereas private sector patient prices were 11.27 and 24.77 times higher, respectively. For both medicines, originator brand prices were about 30 times higher. The highest prices were observed in the lowest income countries. The lowest-paid government worker would need wages from 1-2.6 days' to purchase a month's supply of phenytoin, whereas carbamazepine would cost 2.7-16.2 days' wages. Despite its widespread use in LMICs, WHO/HAI survey data for phenobarbital was only available from a small number of countries. SIGNIFICANCE: In LMICs, availability and affordability of AEDs are poor and may be acting as a barrier to accessing treatment for epilepsy. Ensuring a consistent supply of AEDs at an affordable price should be a priority.

Crafting Immunological Response Using Particulate Vaccines.

To achieve optimal immunogenicity, particulates present a promising vehicle for antigen delivery and have the potential to skew immune response. Particulate vaccine offers several advantages including targeting of antigen to sentinel cells, protection from degradation, sustained release, and itself acts an adjuvant mimics viral structure. Adjuvant presence is vital in overcoming the poor immunogenicity of vaccines, e.g., subunit vaccines. Adjuvants have antigen dose sparing potential and provide danger signals to alert the immune system. Various particulate carriers received attention in the delivery of vaccine antigens such as virus-like particles, liposomes, immunostimulating complexes, and polymeric particles. This review also discussed the properties of particles such as size, shape, and rigidity affecting the immunological outcome. It further highlights the cellular uptake of the particulate vaccine, antigen processing, and its presentation by antigen-presenting cells. For mass vaccination, especially in countries lacking resources, effect of storage temperature condition on stability of vaccine is pivotal. The current COVID-19 pandemic is not showing any signs of abatement and role of nanocarriers are highly relevant in SARS-CoV-2 pandemic as an effective immunization strategy. Eradication of pandemic demands the rapid evaluation of multiple approaches that can provides successful vaccination platform, enabling scalability and global distribution.