The politics of universal health coverage.

The UN has declared universal health coverage an urgent global goal. Efforts to achieve this goal have been supported by rigorous research on the scientific, technical, and administrative aspects of health systems design. Yet a substantial portion of the world's population does not have access to essential health services. There is growing recognition that achieving universal health coverage is a political challenge. However, fundamental concepts from the political science discipline are often overlooked in the health literature. This Series paper draws on political science research to highlight the ways in which politics can facilitate, or stymie, policy reform. Specifically, we present a framework of analysis that explores how interests, ideas, and institutions shape universal health coverage. We then examine key considerations relating to the implementation of relevant policies. This Series paper shows that a political understanding of universal health coverage is needed to achieve health for all.

A Community Health Worker-Based Intervention on Anthropometric Outcomes of Children Aged 3 to 21 Months in Urban Pakistan, 2019-2021.

Objectives. To evaluate the impact of a community health worker-based "in-home growth monitoring with counseling" (IHGMC) intervention on anthropometric outcomes in Pakistan, where 38% of children younger than 5 years are stunted. Methods. We used an individual, single-blind, step-wedge randomized controlled trial and a pure control group recruited at endline. We based the analysis on an intention-to-treat estimation using the coarsened exact matching (CEM) method for sample selection among treatments and the control. We conducted the baseline in July 2019 and completed endline in September-October 2021. We recruited 1639 households (treated: 1188; control: 451) with children aged 3 to 21 months who were residing in an urban informal settlement area. The CEM sample used for analysis numbered 1046 (treated: 636; control: 410). The intervention continued for 6 months. Results. Compared with the control group, the height-for-age z-score in the IHGMC group increased by 0.58 SD (95% confidence interval [CI] = 0.33, 0.83; P = .001) and the weight-for-age z-score by 0.43 SD (95% CI = 0.20, 0.67; P < .01), measured at endline. Conclusions. IHGMC substantially improved child anthropometric outcomes in disadvantaged localities, and this impact persisted during the COVID-19 pandemic. Trial Registration. AER-RCT registry (AEARCTR-0003248). (Am J Public Health. 2023;113(1):105-114. https://doi.org/10.2105/AJPH.2022.307111).

Income-Nutrition Gradient and Intrahousehold Allocation in Rural Pakistan.

OBJECTIVE: To estimate the relationship between household income and child health outcomes for male and female children, aged 0-5 years, in rural Pakistan. METHOD: The study uses 2014 round of Pakistan Rural Household Panel Survey (PRHPS) and regression analyses to estimate the relationship between household income and child health outcomes for male and female children in rural Pakistan. RESULTS AND POLICY IMPLICATIONS: We find that increase in income is associated with an increase in child weight-for-age and weight-for-height z-scores, and reduction in the likelihood of a child being underweight or wasted. However, our results suggest that these gains associated with an increase in income are greater for male children as compared to female children. These differences in income-nutrition gradient can be explained by the gender-differences in consumption of health inputs (e.g., food intake, vaccinations, and nutritional supplements) associated with an increase in income. Our results indicate the need for policy instruments that can encourage an equitable resource allocation within households.

This study documents the gender bias in income-health relationship for children in rural Pakistan. Our results imply that interventions that target poverty alleviation at the household level may not have equitable impacts on all members of the household because of possible 'son-preference'. This suggests that there is a need to design gender-sensitive interventions to ensure that improvements in nutritional outcomes are shared across genders within households.

An analysis of breakthrough seizures and related factors in paediatric epilepsy patients.

OBJECTIVE: To determine the frequency of breakthrough seizures among paediatric patients suffering from epilepsy, and factors related to the precipitation of these seizures. METHODS: The cross-sectional study was conducted from July 1, 2018, to July 1, 2020, at the Combined Military Hospital Lahore and the Military Hospital, Rawalpindi, Pakistan, and comprised children of either gender aged 2-12 years diagnosed with any type of epilepsy presenting at the children outpatient department. Diagnosis of epilepsy was established by either a consultant adult neurophysician or a consultant paediatrician. The presence of breakthrough seizures was assessed by obtaining detailed history from the patient and the primary caregiver. Socio-demographic profile, duration of epilepsy and poly-pharmacy were noted. Data was analysed using SPSS 23. RESULTS: Of the 450 subjects, 259(57.6%) were boys and 191(42.4%) were girls. The overall mean age was 6.353±4.732 years. The presence of breakthrough seizures was noted in 227(50.4%) subjects. Children with young age, with low family income, and those in need of poly-pharmacy showed significantly higher odds for breakthrough seizures (p<0.05). CONCLUSIONS: The incidence of breakthrough seizures in epileptic children was high despite the anticonvulsant agents that were previously effective in controlling seizures.

Discovery of Novel HCV NS5B polymerase inhibitor, 2-(3,4-dimethyl-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-2(4H)-yl)-N-(2-fluorobenzyl)acetamide via molecular docking and experimental approach.

Hepatitis C Virus (HCV) is a viral infection posing a severe global threat that left untreated progresses to end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Moreover, no prophylactic approach exists so far enabling its prevention. The NS5B polymerase holds special significance as the target of intervention against HCV infection. The current study kindles benzothiazine derivatives against HCV NS5B polymerase through in silico and experimental approaches. Following docking, the compound 2-(3,4-dimethyl-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-2(4H)-yl)-N-(2-fluorobenzyl)acetamide was revealed to form effective binding interaction in the proposed site of HCV NS5B with a score of -10 kcal/mol and subsequently was deciphered through molecular dynamics (MD) simulation study which indicated interaction of residues TYR_382, VAL_381 and HIS_467 through hydrophobic interaction and two residues such as GLU_202 and LYS_209 contributed in the formation of water bridges. The subsequent in silico pharmacological analysis revealed its safe drug profile. The cytotoxicity activity of compound 6c indicated to be non-toxic in HepG2 cells at concentration ranges from 0.001-1.0 µmol/L with >80% cell viability and diminished expression of the HCV NS5B to 98% at the dose of 1.0 µmol/L and 90% at 0.5µmol/L. Thus the hit compound 6c might be a potent NS5B polymerase inhibitor required to be validated further through in vivo and preclinical studies.

Calcium hydroxyapatite nanoparticles as a reinforcement filler in dental resin nanocomposite.

The current study focuses on the fabrication of calcium hydroxyapatite (Ca10(PO4)6(OH)2) (HA) in a nanorange having whiskers- and cubic-shaped uniform particle morphology. The synthesized HA particles hold a promising feature as reinforcement fillers in dental acrylic resin composite. They increase the efficacy of reinforcement by length and aspect ratio, uniformity, and monodispersity. Therefore, the acrylic resin was reinforced with the as-synthesized monodispersed HA filler particles (0.2-1 Wt%). The presence of filler particles in the composite had a noticeable effect on the tribological and mechanical properties of the dental material. The morphological effect of HA particles on these properties was also investigated, revealing that cubic-shaped particles showed better results than whiskers. The as-fabricated composite (0.4 Wt%) of the cubic-shaped filler particles showed maximum hardness and improved antiwear/antifriction properties. Particle loading played its part in determining the optimum condition, whereas particle size also influenced the reinforcement efficiency. The current study revealed that particle morphology, particle size, uniformity, etc., of HA fillers, greatly influenced the tribological and mechanical properties of the acrylic resin-based nanocomposite. Improvement in the tribological properties of HA particle-reinforced acrylic resin composites (HA-acrylic resin) followed the trend as AR < CmC < WC < CC.

Psychiatric morbidity among informal caregivers of children suffering from intellectual developmental disorders.

OBJECTIVE: To assess the presence of psychiatric morbidity and associated socio-demographic factors among informal caregivers of children suffering from intellectual developmental disorders. METHODS: The analytical cross-sectional study was conducted at the Neurology Department of a tertiary care hospital in Rawalpindi, Pakistan, from January 1, 2018, to December 31, 2019, and comprised informal caregiver of children diagnosed with intellectual developmental disorders presenting at the paediatric or neurology outpatient clinics of the hospital. Intellectual developmental disorder was diagnosed by consultant neurologists or psychiatrists or paediatricians on the basis of International Classification of Diseases-11 criteria. Psychiatric morbidity in the informal caregiver was assessed using the 12-item general health questionnaire. Data was analysed using SPSS 23, and binary logistic regression was applied to assess association. RESULTS: Of the 500 informal caregivers, 323(64.6%) showed psychiatric morbidity. Increasing age and comorbid epilepsy among the patients were significantly related to the presence of psychiatric morbidity among the informal caregivers (p<0.05). CONCLUSIONS: Majority of informal caregivers of children with learning difficulties were found to have psychiatric morbidity.

CRISPR/CAS9-Mediated Antiviral Activity: A Tool to Combat Viral Infection.

Viruses hijack host cellular receptors and functions for replication, thereby posing a complication in identifying therapeutic targets. The CRISPR/Cas 9 platform has revolutionized gene-editing modalities in a wide range of cells and organisms with high potential in therapeutics. Recently, it has been put to work targeting human pathogenic viruses that interrupt receptors and functions with viral replication. This review encompasses major discoveries in CRISPR/Cas as an antiviral strategy. Additionally, challenges that demand consideration prior to its use in the clinic as part of the antiviral armamentarium are briefly addressed.

Exploring HCV genome to construct multi-epitope based subunit vaccine to battle HCV infection: Immunoinformatics based approach.

Hepatitis C Virus (HCV) infection is a major cause of chronic liver disease, hepatocellular carcinoma, and the single most common indication for liver transplantation. HCV vaccines eliciting specific T-cell responses, have been considered as potent method to prevent HCV infection. Despite several reports on progress of vaccine, these vaccine failed in mediating clinical relevance activity against HCV in humans. In this study we integrated both immunoinformatic and molecular docking approach to present a multiepitope vaccine against HCV by designating 17 conserved epitopes from eight viral proteins such as Core protein, E1, E2, NS2, NS34A, NS4B, NS5A, and NS5B. The epitopes were prioritized based on conservation among epitopes of T cell, B cell and IFN-γ that were then scanned for non-homologous to host and antigenicity. The prioritized epitopes were then linked together by AAY linker and adjuvant (ß-defensin) were attached at N-terminal to enhance immunogenic potential. The construct thus formed were subjected to structural modeling and physiochemical characteristics. The modeled structure were successfully docked to antigenic receptor TLR-3 and In-silico cloning confers the authenticity of its expression efficiency. However, the proposed construct need to be validate experimentally to ensure its safety and immunogenic profile.

Dentin Tubule Occlusion Potential of Novel Dentifrices Having Fluoride Containing Bioactive Glass and Zinc Oxide Nanoparticles.

OBJECTIVE: To compare the in vitro potential of dentin tubule occlusion of two novel experimental dentifrices consisting of fluoride containing bioactive glass (BG) with zinc oxide nanoparticles. MATERIALS AND METHODS: Forty-eight dentin discs (n = 48) were divided into 6 groups (n = 8), based on their brushing dentifrices: Group 1 = artificial saliva (AS; control); Group 2 = fluoride dentifrice (Colgate Palmolive©, UK); Group 3 = experimental nonactive agent dentifrice; Group 4 = experimental dentifrice with 1.5% BG; Group 5 = experimental dentifrice with 4% BG; and Group 6 = BioMinF© dentifrice. Postbrushing, the discs were subjected to acidic challenge with 6% wt citric acid (pH = 4.0) for 1 min. Scanning electron microscope (SEM) and energy-dispersive X-ray (EDX) spectroscopy were performed pre- and post-citric acid challenges, and percentages of tubule occlusion assessed. RESULTS: SEM micrographs of group 1 (AS) show no tubule occlusion (0%), whereas those of groups 2 and 3 show partial tubule occlusion (25 to <50% of tubules occluded). The SEM micrographs of dentifrices containing fluoride-BG (groups 4, 5, and 6) show that most of the tubules (>50 and <100%) were occluded. For all the groups (excluding group 1), pre- and post-citric acid challenge values are statistically significant (p < 0.05). EDX analysis reveals the presence of zinc in experimental dentifrices only. CONCLUSION: The results of novel experimental dentifrices are comparable to those of the BioMinF©, in terms of tubule occlusion. Dentifrices containing BG could serve as an alternative in dentin sensitivity management.

Funding for Abstinence-Only Education and Adolescent Pregnancy Prevention: Does State Ideology Affect Outcomes?

OBJECTIVES: To examine the relationship between adolescent pregnancy-prevention and sexuality and abstinence-only education funding and adolescent birthrates over time. Also, to determine whether state ideology plays a moderating role on adolescent reproductive health, that is, whether the funding has its intended effect at reducing the number of adolescent births in conservative but not in liberal states. METHODS: We modeled time-series data on federal abstinence-only and adolescent pregnancy-prevention and sexuality education block grants to US states and rates of adolescent births (1998-2016) and adjusted for state-level confounders using 2-way fixed-effects models. RESULTS: Federal abstinence-only funding had no effect on adolescent birthrates overall but displayed a perverse effect, increasing adolescent birthrates in conservative states. Adolescent pregnancy-prevention and sexuality education funding eclipsed this effect, reducing adolescent birthrates in those states. CONCLUSIONS: The millions of dollars spent on abstinence-only education has had no effect on adolescent birthrates, although conservative states, which experience the greatest burden of adolescent births, are the most responsive to changes in sexuality education-funding streams.

Relationship between network operators and risky sex behaviors among female versus transgender commercial sex workers in Pakistan.

Unprotected sex among commercial sex workers (CSWs) remains a leading cause of HIV transmission internationally. Previous research on condom use among CSWs has focused on females, with limited research among transgenders or on the role of network operators who mediate paid sexual transactions. We test whether network operators increase the likelihood of condom use among female and transgender CSWs in four Pakistan provinces using the 2011 Integrated Behavioral and Biological Survey. We find that transgender CSWs recruiting clients through network operators had higher odds of consistently using condoms compared with female CSWs recruiting clients through another source (relative OR: 2·80, 95% CI: 1·67, 4·70). While transgender CSWs in Pakistan using network operators have higher rates of condom use, however, this protective effect does not hold among females. This suggests that network operators may be a valuable group to target for HIV prevention efforts.

Interferon-Free Regimen for Hepatitis C: Insight and Management.

The rapid development of direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) therapy dramatically altered the treatment landscape of this disease. The DAA regimen is associated with various advantages including high sustained virological response (SVR) with minimum side effects and low pill load and specific inhibition of viral replication, which lowers dependence on the host cell. This regimen has substantially replaced conventional (interferon) therapy with high cure rates (> 90%) in most HCV populations. This review provides insight into clinical studies of NS3/4A protease inhibitors, NS5B viral polymerase inhibitor (nucleotide and non-nucleotide), and NS5A inhibitors, alone and in combination.

Effectiveness of clobazam on perception, creativity, intelligence, selective and visual memory.

Clobazam belongs to benzodiazepine class and is preferably used against anti-epileptic disorders. However, when used in reduced doses, its ability for improving cognitive functions becomes explicitly evident. This study objectively undertook the task of using the reduced doses of clobazam for proving potentials effects on cognitive functions. The drug, clobazam was administered in "active group" which contained 15 young healthy volunteers. The "placebo group" also entailed 15 subjects and each was administered with placebo drug. The controlled group? also included 15 subjects. All these 45 young healthy subjects were subjected to tests for perceptual learning, creativity, selective memory, visual memory and intelligence. Results clearly demonstrated significant impact of clobazam at the dose of 5mg/day on perceptual learning (P=0.0380), creativity (P=0.0787), memory function (P=0.4920), visual memory (P=0.4816) and intelligence of the subject (P=0.4920). The outcomes highlighted in the studies reviled the positive effects of clobazam when used at reduced doses.

Mechanism of Hepatitis C Virus-Induced Diabetes Mellitus.

The hepatitis C virus (HCV), the most predominant cause of liver failure worldwide, is associated with the development of diabetes mellitus (DM) and insulin resistance (IR), both in vivo and in vitro. DM and IR aggravate the rate of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Most studies have revealed that patients with HCV are at a greater risk of developing type 2 diabetes (T2D), compared with controls or patients with hepatitis B. In the same way, patients with T2D are highly prone to severe HCV clinical outcomes and increased progression to fibrosis and cirrhosis, ultimately leading to HCC. HCV interferes with the insulin-signaling pathway by modulating cellular gene expression such as up-regulation of inflammatory cytokine tumor necrosis factor-α, hypophosphorylation of insulin receptor substrate-1 and -2, phosphorylation of protein kinase B (Akt), up-regulation of gluconeogenic genes, accumulation of lipids, and targeting of lipid storage organelles. Owing to the pathological association between HCV and DM, the possibility of HCV eradication, resulting in reduced morbidity and mortality rate due to T2D, cannot be ruled out. HCV diabetes-associated IR can be targeted for HCV therapy. However, few such studies have revealed that IR minimizes (interferes with) the response rate of interferon/ribavirin treatment.

Female-Headed Households Associated with Lower Childhood Stunting Across Culturally Diverse Regions of Pakistan: Results from a Cross-Sectional Household Survey.

Objectives Early childhood stunting adversely influences long-term cognitive and health outcomes. There is limited evidence on whether female empowerment within households could reduce its prevalence. We investigated this relationship in Punjab, Pakistan, which has high stunting rates and a sizeable proportion of female-headed households, and whether this relationship differed across three provincial regions with diverse cultural attitudes towards the role of women in society. Methods Using cross-sectional data from the 2011 Multiple Indicator Cluster Survey, we identified 13,412 children aged 1-4 from 8985 two-parent households in three culturally distinct regions in Punjab, Pakistan. Logistic regression models assessed whether the likelihood of stunting was associated with female-headed households, a proxy for female empowerment, and whether this relationship differed by region. Regressions controlled for child- and household-level covariates. Results Children had 26% lower odds of stunting among female-headed households (OR 0.74, CI 0.60, 0.90). The interaction term for female-headed households and child stunting by provincial region was not statistically significant, suggesting that the relationship holds across the three culturally distinct regions. Conclusions for Practice Female empowerment was associated with lower rates of stunting among young children, and the results did not vary by provincial region. This suggests that women can play important roles as agents of change, even in areas where females have limited freedoms. Greater investments in public education and awareness campaigns to improve health literacy might have important spillover effects for child health and improve the success of existing public health interventions targeting childhood stunting.

Implementing Updated Recommendations on Hepatitis C Virus Screening: Translating Federal Guidance Into State Practice.

CONTEXT: Chronic viral hepatitis is a leading infectious cause of death. The Centers for Disease Control and Prevention (CDC) released updated recommendations for hepatitis C virus testing, including recommending that all individuals born between 1945 and 1965 be tested once. States' consistency with these national testing guidelines is unknown. OBJECTIVE: To evaluate the extent to which state health departments have current hepatitis C virus testing recommendations listed on their Web sites, consistent with national guidelines. DESIGN: The CDC guidelines were reviewed to identify the risk groups recommended for or against testing. State health department Web sites (50 US states, the District of Columbia, and Puerto Rico) were then systematically reviewed to classify whether, for each risk group, testing is recommended, not recommended, or with unclear recommendations. MAIN OUTCOME MEASURE: States' consistency with national recommendations for each risk group mentioned by the CDC. RESULTS: Among the risk groups that the CDC currently recommends for testing, 50% of states updated their Web sites to include individuals born between 1945 and 1965. All states recommend testing current or former injection drug users, but only 58% recommended testing HIV-positive individuals. Among the risk groups for which the CDC has issued uncertain recommendations, states most frequently recommended testing individuals with tattoos or body piercing done with unsterile materials (46%) or with a history of multiple sex partners (31%). CONCLUSIONS: There is substantial variation in state Web sites' consistency with the CDC guidelines. The public health importance of risk factors is not associated with their inclusion in Web content. Improving the uptake of these recommendations and the manner in which they are conveyed to the public are critical to implementing the national viral hepatitis action plan, thereby increasing diagnoses and averting new infections.

ONION PEEL APPEARANCE IN BALOS CONCENTRIC SCLEROSIS--A VARIANT OF MULTIPLE SCLEROSIS.

Balo's concentric sclerosis (BCS) is a variant of multiple sclerosis (MS). It may present as a lesior clinically and radiologically indistinguishable from brain tumour particularly on computerized tomography (CT) scans. Diagnosis only gets clear when magnetic resonance imaging and spectroscopy (MRI & MRS) and brain biopsy is done. We report a case of 30 year old male with progressive headache and left hemi paresis for 3 weeks. There was upper motor neuron (UMN) facial palsy on the left with bilateral papilledema. CT scan of brain showed large hypo-dense area in right frontoparietal lobe consistent with brain tumour. On MRI the diagnosis of BCS was made on basis of concentric lesions of myelinated and demyelinated rings. Demyelination wa confirmed on brain biopsy.

Calcineurin and mTOR inhibitors in kidney transplantation: integrative metamodeling on transplant survival and kidney function.

In our study, we examined the efficacy of mTOR (mammalian target of rapamycin) inhibitors, specifically rapamycin (Rap), compared to calcineurin inhibitors (CNIs) in kidney transplantation. By conducting a comprehensive search across reputable databases (EMBASE, Scopus, PubMed, Cochrane, and Crossref), we gathered data for a six-month post-transplantation period. Our analysis revealed that mTOR inhibitor administration resulted in improved glomerular filtration rate (GFR) and serum creatinine levels. However, it is important to note that the mTOR inhibitor group had a higher incidence of acute rejection after biopsy. Through molecular modeling, we observed that Rap exhibited a superior binding affinity for mTOR compared to CNIs' binding to calcineurin, probably contributing to the transplant rejection. Our meta-analysis supports the cautious use of an optimal mTOR inhibitor in conjunction with careful consideration of clinical features when minimizing CNIs early in the transplantation process. This is because mTOR inhibitors have complementary mechanisms of action, a low nephrotoxicity profile, and favorable outcomes in serum creatinine and GFR, which contribute to improved transplant survival.

First reported case: Uncommon presentation of Burkitt lymphoma as perineal ulceration in a young patient.

INTRODUCTION AND IMPORTANCE: Burkitt lymphoma (BL) is an aggressive subtype of non-Hodgkin lymphoma with a predilection for pediatric patients, known for its rapid growth and MYC oncogene-associated chromosomal translocations. CASE PRESENTATION: A 33-year-old male presented with a perineal ulcerated wound, initially misdiagnosed as a musculoskeletal injury. Imaging and histopathological analysis eventually confirmed BL, leading to the initiation of high-dose chemotherapy. CLINICAL DISCUSSION: BL is characterized by its rapid growth, typically as masses in the abdomen or jaw. Nevertheless, atypical presentations can lead to diagnostic delays, underscoring the importance of considering BL even in the absence of classic symptoms. Swift recognition and accurate diagnosis are critical for initiating timely chemotherapy. Comprehensive clinical evaluation, advanced imaging, and histopathological analysis are pivotal in confirming the diagnosis. CONCLUSION: This unique case of BL with a perineal mass presentation emphasizes the necessity of considering BL as a potential diagnosis in atypical cases, highlighting the importance of early recognition and appropriate therapeutic strategies. Healthcare professionals should be aware of the potential for unusual BL presentations.