Willingness to Pay for Community-Based Healthcare Insurance Schemes in Developing Countries: A Case of Lahore, Pakistan

BACKGROUND: Healthcare costs and poverty are significant barriers to achieving universal access to healthcare. Thus, Community-Based Health Insurance Schemes (CBHIS) are regarded as an influential instrument for providing access to healthcare. For this purpose, this study was carried out in order to assess the community’s Willingness to Pay (WTP) for CBHIS and its determinants among the residents of Lahore City.METHODS: A cross-sectional study was adopted during the period of May 2018 to August 2018 to conduct a standardized questionnaire survey among targeted population of Lahore. A total of 250 households from lower, middle and upper-middle-class areas were approached randomly from which 200 participated in the survey, rendering a response rate of 90.9%. Sample size was determined by using single population proportion formula assuming 5% margin of error and 95% Confidence Interval (CI). Moreover, multiple regression analysis, Pearson’s correlation and t-test were employed to determine relationships between different variables affecting WTP.RESULTS: Sixty-four percent of the respondents were willing to pay for CBHIS. Among the remaining thirty-six% of unwilling the community, income level (p< 0.05, CI=0.34 to 1.11) and education level (p< 0.05, CI=0.52-1.37) were significant predictors of WTP. Moreover, strong positive relation (p<0.05) between people’s awareness and WTP for CBHIS was witnessed. The findings further suggested that the larger population of the willing community was not willing to pay more than 5000 Rs annually.CONCLUSION: Henceawareness level of the community regarding the benefits of CBHIS is a major hindrance. The key policy priority is to increase the community’s awareness regarding the benefits of CBHIS and to increase willingness to pay rate among public.&nbsp

Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1

Background Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role. Objective To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family. Methods Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of Gnpnat1 gene knockdown in primary rat chondrocytes. Results The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in GNPNAT1, segregating with the disease. Glucosamine 6-phosphate N-acetyltransferase, encoded by the highly conserved gene GNPNAT1, is one of the enzymes required for synthesis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation. Knockdown of Gnpnat1 by siRNAs decreased cellular proliferation and expression of chondrocyte differentiation markers collagen type 2 and alkaline phosphatase, indicating that Gnpnat1 is important for growth plate chondrocyte proliferation and differentiation. Conclusions This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in GNPNAT1. Our data suggest that GNPNAT1 is important for growth plate chondrogenesis.Peer reviewe

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C-terminal to the motor domain, in agreement with a genotype-phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

Clinical, radiographic and molecular characterization of two unrelated families with multicentric osteolysis, nodulosis, and arthropathy

Abstract Background Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder characterized by marked progressive bone loss and joint destruction resulting in skeletal deformities. MONA is caused by MMP2 deficiency. Here we report clinical and molecular analyses of four patients in two families from Pakistan and Finland. Methods Clinical analyses including radiography were completed and blood samples were collected. The extracted DNA was subjected to whole-exome analysis or target gene sequencing. Segregation analyses were performed in the nuclear pedigree. Pathogenicity prediction scores for the selected variants and conservation analyses of affected amino acids were observed. Results The phenotype in the four affected individuals was consistent with multicentric osteolysis or MONA, as the patients had multiple affected joints, osteolysis of hands and feet, immobility of knee joint and progressive bone loss. Long-term follow up of the patients revealed the progression of the disease. We found a novel MMP2 c.1336 + 2T > G homozygous splice donor variant segregating with the phenotype in the Pakistani family while a MMP2 missense variant c.1188 C > A, p.(Ser396Arg) was homozygous in both Finnish patients. In-silico analysis predicted that the splicing variant may eventually introduce a premature stop codon in MMP2. Molecular modeling for the p.(Ser396Arg) variant suggested that the change may disturb MMP2 collagen-binding region. Conclusion Our findings expand the genetic spectrum of Multicentric osteolysis nodulosis and arthropathy. We also suggest that the age of onset of this disorder may vary from childhood up to late adolescence and that a significant degree of intrafamilial variability may be present

Thyroid function analysis in COVID-19: A retrospective study from a single center.

Background and objectiveCoronavirus disease 2019 (COVID-19) is an on-going epidemic with a multitude of long-ranging effects on the physiological balance of the human body. It can cause several effects on thyroid functions as well. We aimed to assess the lasting sequelae of COVID-19 on thyroid hormone and the clinical course of the disease as a result.MethodsOut of 76 patients, 48 patients of COVID-19 positive and 28 patients of COVID-19 negative polymerase chain reaction (PCR) were assessed for thyroid functions, IL-6, and Procalcitonin between moderate, severe, and critical pneumonia on HRCT.ResultsSeventy-five percent of patients with COVID-19 had thyroid abnormalities and higher IL-6 levels (76.10 ± 82.35 vs. 6.99 ± 3.99, 95% CI 52.18-100.01, P-value ConclusionThis pilot study from Pakistan demonstrates that changes in serum TSH and TT3 levels may be important manifestations of the courses of COVID-19 pneumonia

Foliar Application of Potassium Mitigates Salinity Stress Conditions in Spinach (<i>Spinacia oleracea</i> L.) through Reducing NaCl Toxicity and Enhancing the Activity of Antioxidant Enzymes

Agronomic biofortification is the purposeful utilization of mineral fertilizers to increase the concentration of desired minerals in edible plant parts for enhancing their dietary intake. It is becoming crucial to enhance the dietary intake of K for addressing hidden hunger and related health issues such as cardiac diseases and hypertension. This study was designed to enhance the potassium concentration in edible parts of spinach through its foliar application under saline environment. The salinity levels of electrical conductivity (EC) = 4, 6, and 8 dS m−1 were applied using sodium chloride (NaCl) along with control. The levels of K for foliar sprays were 5 and 10 mM, along with control. The present experiment was performed under two factorial arrangements in a completely randomized design (CRD). After 60 days of sowing, the crop was harvested. Data regarding growth, ionic, physiological, and biochemical parameters, i.e., shoot dry weight, relative water content, electrolyte leakage, total chlorophyll content, tissue sodium (Na) and K concentration, activities of superoxide dismutase (SOD), and catalase (CAT) were recorded and those were found to be significantly (p ≤ 0.05) affected by foliar application of K on spinach under saline conditions. The highest growth, physiological and biochemical responses of spinach were observed in response to foliar-applied K at 10 mM. It is concluded that agronomic bio-fortification by foliar use of K can be a useful strategy to increase tissue K intakes and minimize Na toxicity in the vegetables studied under saline conditions