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Abstract Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S‐transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S‐transferase T1 (GSTT1) and glutathione S‐transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross‐sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(−) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30–3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(−) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43–5.87, P = 0.003). The GSTT1(−) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(−) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(−) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(−) null genotype in the North Indian population.

Background The objective of our study was to derive an objective assessment scale for three-dimensional (3D) qualitative and quantitative evaluation of secondary alveolar bone grafting (SABG) using cone-bone computed tomography (CBCT) in patients with unilateral cleft lip and palate (UCLP). Methods CBCT scans for pre- and 3-month post-SABG were reviewed for bone volume, height, width, and density of the bony bridge formed in the cleft defect in 20 patients with UCLP. Basic descriptive and principal component analysis was used to extract the various sub-components of the scale. Spearman's correlation was used to check the validity of the scale, and intra-class coefficient (ICC) and Cronbach's α were calculated to establish the reliability and retest applicability of the scale. Results Each CBCT scan was assessed in five areas: cementoenamel junction (CEJ), root apex, root midpoint, 3 and 6 mm below CEJ, and tabulated in percentiles of 20, 25, 40, 50, 60, and 75 for all the parameters (bone volume, density, and width). These scores were validated when correlated to the scale given by Kamperos et al. Cronbach's α for the domains demonstrated acceptable to excellent internal consistency. The ICC showed good test–retest reliability having a range of scores from 0.89 to 0.94. Conclusion The proposed scale for the 3D assessment of SABG in patients with UCLP provides gradation for the objective assessment of the bony bridge. This gradation enables the qualitative and quantitative assessments of the bony bridge, thus allowing each clinician to judge SABG more conclusively.

Mycobacterium tuberculosis is an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The aetiology of tuberculosis has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphism on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. PCR RFLP was performed to identify the genotype of the IL4RAQ576R and IL-8 +781C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p= 0.03) in tuberculosis. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781C/T, showed a significant association. Moreover, different combinations of the SNPS were made, and the 3 risk allele shows a significant protective role (p=0.02). There is considerable evidence which shows that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against tuberculosis, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with tuberculosis. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing tuberculosis.

PINK1/parkin-dependent mitophagy initially involves (phospho)ubiquitin-directed proteasome-dependent degradation of certain outer mitochondrial membrane (OMM) proteins (e.g. mitofusins) and the recruitment of autophagy adaptors to a group of ubiquitinated OMM proteins, eventually leading to autophagic removal of damaged mitochondria in stressed cells. Here we provide evidence that mitochondrial degradation occurs via stepwise delivery of separate mitochondrial sub-compartments for autophagic degradation. OMM and inner mitochondrial material appears to become separately isolated for autophagolysosomal degradation, not only in parkin-overexpressing HeLa cells but also in cells that express endogenous parkin (human embryonic kidney cells and neural progenitor cells) with slower mitophagy kinetics. The remaining inner mitochondrial material becomes degraded only after much prolonged membrane depolarization, potentially involving another proteasome-sensitive step. The present combined microscopy and proteomics analyses support the idea that cell stress-induced parkin-dependent mitophagy is a complex multi-step process with distinct mitochondrial sub-compartments being separately targeted for autophagic degradation. Abbreviations: BafA, Bafilomycin A; CCCP, carbonyl cyanide 3-chlorophenylhydrazone; COX IV, cytochrome c oxidase subunit IV; CS, citrate synthase; DMEM, Dulbecco’s modified Eagle’s medium; EGFP, enhanced green fluorescent protein; FBS, fetal bovine serum; IF, immunofluorescence; IMM, inner mitochondrial membrane; KO, knock-out; LC3, microtubule-associated protein 1 light chain 3; MDVs, mitochondria-derived vesicles; MFN, mitofusin; NPCs, neural progenitor cells; OMM, outer mitochondrial membrane; p62/SQSTM, 62kDa protein sequestosome-1; PBS, phosphate-buffered saline; PINK1, phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1; RT, room temperature; SSBP1, single-stranded DNA binding protein 1; TAX1BP1, Tax1-binding protein 1; TEM, transmission electron microscopy, TOM20, translocase of outer mitochondrial membrane 20kDa subunit; TOM70, translocase of outer mitochondrial membrane 70kDa subunit; Ub, ubiquitin; UPS, ubiquitin proteasome system; VDAC, voltage-dependent anion-selective channel protein; WB, Western blot; WT, wild-type

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterised by a modified inflammatory response to chronic irritants which is often associated with some degree of systemic inflammation. Exacerbations in COPD are characterized by exaggeration of the ongoing inflammation. A number of inflammatory mediators are found to be raised in COPD exacerbations but most of them are expensive and not readily available. The Neutrophil-lymphocyte Ratio (NLR) is a rapid, easy and cheap biomarker that has been shown to be raised in patients of COPD. Aim: To evaluate the role of NLR in patients of stable and acute exacerbation of COPD. Materials and Methods: This cross-sectional observational study was conducted in Department of Pulmonary Medicine at Government Medical College, Patiala, Punjab, India. Study included 150 patients of stable COPD, 150 patients of Acute Exacerbation COPD (AECOPD) and 100 subjects as controls. NLR was calculated from a peripheral blood sample of the study participants. Continuous variables were summarised as mean with standard deviation and compared between groups using Unpaired t-test. A p-value

Post-translational modifications are critical for regulating the DNA damage response. Here, the authors identify a methylation-deubiquitination crosstalk between methyltransferase PRMT1 and deubiquitinase USP11, showing that the enzymes regulate each other’s functions in DNA repair.

The Rho GTPase Miro1, located at the mitochondrial outer membrane is known to properly distribute mitochondria to synapses, aid calcium buffering and initiate PINK1-Parkin mediated mitophagy. Several heterozygous RHOT1/Miro1 variants were identified in sporadic Parkinson’s disease patients. Miro1 R272Q is located within a calcium binding domain, but the functional outcome of this point mutation and its contribution to the development of disease are unclear. To address this, we introduced a heterozygous RHOT1/Miro1 R272Q point mutation in healthy induced pluripotent stem cells. In dopaminergic neurons, Miro1 R272Q does not affect Miro1 protein levels, CCCP-induced mitophagy, nor mitochondrial movement yet causes the fragmentation of mitochondria with reduction of cristae and ATP5A. Inhibition of the mitochondrial calcium uniporter phenocopied Miro1 R272Q cytosolic calcium response to Thapsigargin in active neurons, a similar effect was observed during the calcium buffering phase in Miro1 knockdown neuroblastoma cells. Altered mitochondrial calcium regulation is associated with reduced mitochondrial respiration and reduced catecholamine neurotransmitter uptake. Synaptic changes are not coupled to dopamine distribution or dopamine transporters but are linked to Miro1 R272Q-related calcium handling via the mitochondria concomitant with defective dopamine regulation at the mitochondrial surface by monoamine oxidase. We conclude that the Miro1 R272Q heterozygous point mutation dampens mitochondrial-calcium regulation and mitochondrial capacity via events at the outer membrane that are sufficient to disrupt dopaminergic function.

Determination of viral load through cycle threshold (Ct) values may act as a predictor of severity and outcomes in patients with corona virus disease 2019 (COVID-19). However, variable literature is available regarding this relationship. Our study attempted to explore this association and the effect of various socio-demographic and clinical parameters on severity and outcome of COVID-19. Retrospective analysis of records of 731 patients whose nasopharyngeal/ oropharyngeal swabs were subjected to cartridge based nucleic acid amplification (CBNAAT) on Cepheid Xpert Xpress SARS-Cov-2 was done. Cycle threshold (Ct) values of N2 and E genes were studied in relation to severity and outcome of COVID-19. The viral load as determined by Ct values was classified as high (32). Association of socio-demographic and clinical parameters with respect to severity and outcome was also studied. Severity and mortality were significantly more in elder individuals, those belonging to the rural background, those with symptoms >7 days in duration before presentation and those with increasing number of co-morbidities (Severity: p32, in comparison when it was upto 25, and when between 25.1 and 32 (severity: p=0.032 and 0.003 respectively, mortality: p=0.018 and

Abstract Background CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as “two-donor floxing” method). Results We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach. Conclusion We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

Mediastinal lymphadenopathy is often associated with tuberculosis, especially in a high burden country like India. We present a case of an asymptomatic female, who had mediastinal lymphadenopathy and middle lobe collapse, both of which pointed towards a diagnosis of tuberculosis. Patient was later diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA) on basis of clinical, radiological and serological findings. Hence, even in a high burden country and in background of bronchial asthma, ABPA should be kept as a differential diagnosis in patients presenting with mediastinal lymphadenopathy

Timing of treatment of protruding premaxilla in a bilateral cleft lip and palate (BCLP) patient is an issue of dilemma. Fracture of the premaxillary segment following trauma in a patient with complete BCPL is presented. Salvaging the mobile premaxilla becomes an emergency. Surgical management of such a fracture has been discussed in a patient with repaired cleft lip and palate in the light of recent literature.

The present case report deals with the per-vaginal delivery of a lipomatous fetus associated with pseudohypertrophy (steatosis) of shoulder and dropsy of fetal membranes in a river buffalo.

The current case report gives the brief information about fetal maceration in a non-descript six years aged cow and its successful management through lateral oblique (flank) approach of laparo-hysterotomy. The animal had a history of eleven-month gestation without any sign of parturition. Initially, the animal was suspected for mummification since there was no genital discharge and completely closed cervix. Upon transrectal ultrasonography the case was confirmed with fetal maceration. Lateral oblique laparo-hysterotomy was decided to perform for delivery of macerated and reabsorbed fetus. Animal recovered uneventfully after proper post-operative care and management.

Present study reports successful management of a case of mucometra associated with cystic ovarian follicles and uterine unicornis in a Sahiwal cow.

A case of dystocia due to Cephalo-thoraco-abdomino-pygopagus monstrosity condition in a Murrah buffalo was brought to the clinics and the fetus was removed by caesarean section.