Pandemic-associated pernio harbors footprints of an abortive SARS-CoV-2 infection.

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

Effect of intensive training and education of health care workers on the maintenance bundle of venous access devices in critically ill patients at a tertiary care academic hospital.

BACKGROUND: The maintenance bundle of care for all venous access devices (peripheral intravenous catheters, PIVC; central venous catheters, CVCs; hemodialysis ports) is important to prevent secondary sepsis in critically ill patients. This quality improvement project analyzed the effect of intensive training and education of health care workers (HCWs) on maintenance bundles for venous access devices. METHODS: The study period comprising of preintervention phase (3-months) included 25 random visits to the intensive care unit for point observations regarding maintenance of all venous access devices in-situ in all intensive care unit patients on the day of the visit. The observations were categorized as appropriate or inappropriate practices based on American Society of Anesthesiologists (ASA) guidelines for CVC 2020, INICC guidelines for PIVC 2017, and Australian Commission on Safety and Quality in Health Care (ACQHCS) for PIVC and hemodialysis ports, December 2019. While the intervention phase (1-month) comprised intensive training and education of HCWs, postintervention phase 3 (3-months) included similar visits and point observations as during the preintervention phase. RESULTS: The maintenance of PIVC improved significantly in terms of the condition of site (from 82.7% appropriate observations to 97.8%, P < .05); condition of connectors (45.7%-56.8%, P < .05), and any attached unused IV sets (90.5%-98.56%, P < .05). For CVC, there was significant improvement in condition of insertion site (66%-94%, P < .01); condition of connectors (0%-44.37%, P < .01); fixation (91%-99.3%, P < .05); any attached unused IV sets (38.9%-97.3%, P < .01) and knowledge of HCW (96.52%-100%, P = .05). For hemodialysis ports, no significant improvement was observed. CONCLUSIONS: Intensive training and education of HCWs led to significant improvement in the maintenance bundle of care for PIVC and CVC.

Genetic variation and population structure of five ethnic groups from Punjab, North-West India: Analysis of MHC class I polymorphic Alu insertions (POALINs).

Genetic variation and differentiation of five ethnic groups from Punjab, North-West India was characterized by analyzing data on polymorphic Alu insertions (POALINs) within the class I genomic region of major histocompatibility complex (MHC), which is completely non-existent in Indian population. The haplotype frequency, distribution and heterozygosity among these groups and their potential implications in molecular anthropology and evolutionary studies were also determined. A total of 479 unrelated healthy individuals representing five different ethnic groups: Banias, Brahmins, Khatri, Jat Sikhs and Scheduled Castes were genotyped for five MHC Alu elements (AluHG, AluMICB, AluHJ, AluTF and AluHF) using polymerase chain reaction (PCR). All the loci were found to be polymorphic among the studied populations. No significant deviation from Hardy-Weinberg equilibrium was observed, except for the AluHJ locus in Brahmins. The POALINs varied in allele frequency between 0.0260 and 0.4427. The average heterozygosity among the studied groups ranged from 0.1937 in Banias to 0.2666 in Jat Sikhs. The genetic differentiation among the studied groups was observed to be of the order of 0.01302. Single POALIN haplotypes were found to be more frequent than multiple POALIN haplotypes. The results of inter-population differentiations, haplotype frequencies, genetic distances, multidimensional scaling, phylogenetic and structure analyses indicated close genetic relationships between the five ethnic groups of Punjab, North-West India. Analyses of polymorphic Alu loci of MHC genomic region may represent reliable information about the ancestry, demographic history and geographic origins of the various human populations, facilitating better understanding of the evolutionary, forensic and epidemiological prospective.

Association of PGC-1α gene with type 2 diabetes in three unrelated endogamous groups of North-West India (Punjab): a case-control and meta-analysis study.

PGC-1α (Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha) plays a key role in glucose homeostasis inside liver and muscle. The impact of six polymorphisms of PGC-1α with Type 2 Diabetes (T2D) susceptibility was evaluated on 1125 samples comprising of 554 T2D cases and 571 controls among three endogamous groups (Bania, Brahmin and Jat Sikh) of North-West India (Punjab). Single-locus analysis showed a significant differential pattern of genetic association of PGC-1α among studied groups emphasizing the role of ethnicity towards disease susceptibility. Haplotypes G-A-G-G-C-C in Bania group; G-G-G-G-C-A in Brahmin; G-A-A-G-T-C, G-G-G-G-T-C in Jat Sikh groups conferred ~ two to fivefold increased T2D risk. Intriguingly, the haplotype combination G-A-G-G-C-C provided T2D risk in Banias whereas it played a protective role in Brahmins reflecting the role of ethnic heterogeneity. In the secondary structure prediction of mRNA, slight free energy change along with structural changes was observed between the wild and variant allele of rs3736265, rs8192678 and rs2970847 loci. Meta-analyses conducted on rs8192678 and rs2970847 variants illustrated the overall effect of minor alleles providing a higher risk for the T2D development. Divergence in genetic variants and haplotype combinations associated with T2D risk among studied groups is inferred from the present dataset, which strongly highlights the combinatorial effect of diverse ethnic background of the population under study with genetics towards susceptibility to complex diseases like T2D.

Associating genetic variation at Perilipin 1, Complement Factor D and Adiponectin loci to the bone health status in North Indian population.

Osteoporosis, the most common bone metabolic disease affecting nearly 200 million people worldwide is under the strong influence of genetic components. Simultaneously, adipogenesis and osteogenesis are two highly coordinated processes imperative for the maintenance of bone quality and quantity, where any perturbation leads to pathological conditions of obesity, osteopenia and osteoporosis. To delineate this adipogenic-osteogenic connection, a total of 254 cases (T-score<-1.0 SD) and 250 age, gender and ethnicity matched healthy controls (T-score≥-1.0 SD) were recruited from North India after analyzing bone health status employing quantitative ultrasound (QUS) bone densitometer. The genetic variants of Perilipin 1 (PLIN1), Complement Factor D (CFD) and Adiponectin (ADIPOQ) were genotyped using the PCR-RFLP/ARMS-PCR approach. Subjects with CC+CT (PLIN1 rs2304795) and CC+CG (CFD rs1683563) genotypes conferred nearly 1.54-1.87 fold increased risk towards bone deterioration. Predicted RNA secondary structures of rs2304795 corroborated the risk associated with wild type C allele. G allele carriers at the ADIPOQ locus (rs1501299) were more likely to have a lower bone health (1.57-fold). Haplotype analysis revealed the ADIPOQ variants rs1501299 and rs3774261 in slight linkage disequilibrium (LD), nonetheless G/G haplotype was associated with increased risk. 3-locus and 5-locus gene-gene interaction models revealed a greater likelihood of bone deterioration. In conclusion, certain variants of adipogenic genes might serve as potential biomarkers for determining the genetic predisposition towards bone loss in the North Indian population, further, emphasizing the role of impaired metabolism in bone health.

Genetic differentiation and population structure of five ethnic groups of Punjab (North-West India).

The state of Punjab in the North-West part of India has acted as the main passage for all the major human invasions into the Indian subcontinent. It has resulted in the mixing of foreign gene pool into the local populations, which led to an extensive range of genetic diversity and has influenced the genetic structure of populations in Punjab, North-West India. The present study was conducted to examine the genetic structure, relationships, and extent of genetic differentiation in five Indo-European speaking ethnic groups of Punjab. A total of 1021 unrelated samples belonging to Banias, Brahmins, Jat Sikhs, Khatris, and Scheduled castes were analyzed for four human-specific Ins/Del polymorphic loci (ACE, APO, PLAT, and D1) and three restriction fragment length polymorphisms ESR (PvuII), LPL (PvuII), and T2 (MspI) using Polymerase chain reaction (PCR). All the loci were found to be polymorphic among the studied populations. The frequency of the Alu insertion at APO locus was observed to exhibit the highest value (82.6-96.3 %), whereas D1 exhibited the lowest (26.5-45.6 %) among all the ethnic groups. The average heterozygosity among the studied populations ranged from 0.3816 in Banias to 0.4163 in Khatris. The FST values ranged from 0.0418 to 0.0033 for the PLAT and LPL loci, respectively, with an average value being 0.0166. Phylogenetic analysis revealed that Banias and Khatris are genetically closest to each other. The Jat Sikhs are genetically close to Brahmins and are distant from the Banias. The Jat Sikhs, Banias, Brahmins, and Khatris are genetically very distant from the Scheduled castes. Overall, Uniform allele frequency distribution patterns, high average heterozygosity values, and a small degree of genetic differentiation in this study suggest a genetic proximity among the selected populations. A low level of genetic differentiation was observed in the studied population groups indicating that genetic drift might have been small or negligible in shaping the genetic structure of North-West Indian Populations.

Analysis of ANKKI (rs1800497) and DRD2 (rs1079597, rs1800498) variants in five ethnic groups from Punjab, North-West India.

Dopamine D2 receptor (DRD2) is one of the essential neurotransmitters in the brain studied extensively in the field of psychiatric disorders, alcoholic behaviors and Pharmacology. It is also a promising gene for studying the evolutionary and genetic variation among populations. The present study was an attempt to understand the extent of genetic variation among five different ethnic groups (Bania, Brahmin, Jat Sikh, Khatri and Scheduled caste) of Punjab (North West India). A total of 1012 individuals belonging to the above mentioned groups were analyzed for three TaqI Polymorphic loci of DRD2 and ankyrin repeat and kinase domain containing 1 (ANKKI) using the allele frequencies and haplotype frequency distribution pattern. All the three loci were found to be polymorphic among the studied populations. The average heterozygosity for all loci in these ethnic groups was fairly substantial ranging from 0.3936 to 0.4986. The genetic differentiation among the population was observed to be in order of 0.0053.Among of the eight studied haplotypes, only six were shared by all the ethnic groups. TaqID and TaqIB loci were reported to be in significantly higher linkage disequilibrium (LD) in Scheduled Caste only, whereas TaqIA and TaqID showed modest LD in Brahmin, Jat Sikh and Khatri. Multidimensional scaling analysis revealed that the studied ethnic groups formed a close cluster, suggesting similar genetic structure of these populations which are in close proximity with other Indo European speaking North Indian and western Indian population groups. Overall this study highlights the genomic uniformity among the ethnic groups of Punjab (North-West India) owing to their common ancestral history and geographical closeness.

Ethnic differences in CAPN10 SNP-19 in type 2 diabetes: a North-West Indian case control study and evidence from meta-analysis.

Summary Calpain 10 (CAPN10) variants have been associated with the genetic susceptibility to type 2 diabetes (T2D). In the present case-control study, we analysed the distribution of SNP-19 insertion/deletion (I/D) polymorphism in a total of 607 samples (103 T2D cases and 102 healthy controls) from Brahmin; (100 T2D cases and 100 healthy controls) from Bania and (100 T2D cases and 102 healthy controls) from Jat Sikh ethnic groups of the North-West Indian population. Increased frequency of I allele and II genotype was found in T2D in Brahmin ethnic group [P = 0·003, OR = 2·83 (1·43-5·61 at 95% CI)]. Significant correlation between II genotype and body mass index (BMI) was also observed [P = 0·003, OR = 3·31 (1·52-7·20 at 95% CI)]. No association for the genotypes and alleles was seen in Banias and Jat Sikhs. Our data suggests that SNP-19 I/D variation in the CAPN10 gene is modulated by ethnicity and influences the susceptibility to T2D in the North-West Indian population. We also performed a meta-analysis of relevant studies to assess the validity of this association. Data from 13 case-control studies with 15 760 samples comprising of 8395 T2D cases and 7365 controls were finally analysed. Significant heterogeneity between individual studies was evident in dominant and codominant models. The results of present meta-analysis indicate an association of T2D with carriers of DD genotype of CAPN10 I/D polymorphism. However, further analyses on a larger sample size are required to establish a conclusive association in meta-analysis.

C-reactive protein + 1059 G>C polymorphism in type 2 diabetes and coronary artery disease patients.

Human C-reactive protein (CRP) is an acute phase reactant involved in chronic and acute inflammation. CRP is associated with metabolic syndrome, obesity, atherosclerosis, unstable angina, insulin resistance and diabetes. The present study evaluates the association of + 1059 G>C silent polymorphism in exon 2 of CRP gene in 581 cases [CAD (206), T2D (266), T2D with CAD (109)] and 235 controls in the population of Punjab (North-West India). The frequency of + 1059 G allele is highest in CAD (98.3%) followed by T2D (98.1%), T2D + CAD cases (97.7%) and controls (94.7%). G-allele is associated with increased risk of T2D [P = 0.003, OR = 2.93 (1.39-6.17)] and CAD [P = 0.004, OR = 3.25 (1.39-7.60)] in comparison to controls. Recessive model shows that GG genotype increases the risk of CAD by 4 fold (P = 0.003, OR = 4.19, 1.62-10.80), T2D by 3 fold (P = 0.008, OR = 3.23, 1.36-7.60) and T2D + CAD by 3.5 fold (P = 0.029, OR = 3.64, 1.14-11.66). Factor analyses show that BMI, WC, and WHR are core predictors for CAD and T2D, whereas CHO, TG and VLDL for T2D + CAD. The present study concludes that GG genotype of CRP + 1059 G>C polymorphism and clustering of obesity and dyslipidemia underlie the risk towards CAD, T2D and T2D + CAD in the North-West Indian population of Punjab.