Annulation-Induced Hidden Reactivity of the 1,2,4-Triazole Backbone.

Triazoles are an important class of compounds with widespread applications. Functionalization of the triazole backbone is thus of significant interest. In comparison to 1,2,3-triazoles, C-H activation-functionalization of the congeners 1,2,4-triazoles is surprisingly underdeveloped. Indeed, no such C-H activation-functionalization has been reported for 4-substituted 1,2,4-triazole cores. Furthermore, although denitrogenative ring-opening of 1,2,3-triazoles is well-explored, 1,2,4-triazole/triazolium substrates have not been known to exhibit N-N bond-cleaving ring-opening reactivity so far. In this work, we unveiled an unusual hidden reactivity of the 1,2,4-triazole backbone involving the elusive N-N bond-cleaving ring-opening reaction. This new reactivity was induced by a Satoh-Miura-type C-H activation-annulation at the 1,2,4-triazole motif appended with a pyridine directing group. This unique reaction allowed ready access to a novel class of unsymmetrically substituted 2,2'-dipyridylamines, with one pyridine ring fully-substituted with alkyl groups. The unsymmetrical 2,2'-dipyridylamines were utilized to access unsymmetrical boron-aza-dipyridylmethene fluorescent dyes. Empowered with desirable optical/physical properties such as large Stokes shifts and suitable hydrophobicity arising from optimal alkyl chain length at the fully-substituted pyridine-ring, these dyes were used for intracellular lipid droplet-selective imaging studies, which provided useful information toward designing suitable lipid droplet-selective imaging probes for biomedical applications.

Validation of determinate (dt) gene-based DNA marker in inter-specific hybrid sesame and in-silico analysis of the predicted dt protein structures.

Determinacy is a desirable trait in sesame, an important oilseed crop. We have developed an inter-specific hybrid between basally branched indeterminate cultivated Sesamum indicum genotype and wild S. prostratum with no branching yet synchronous pods on the shoot. The hybrid and a few exotic sesame germplasms were successfully screened with a determinacy (dt) gene-based DNA marker. In-silico translation of the partial coding sequences of the dt gene from the two contrasting parent genotypes revealed an SNP (V159A) in S. prostratum. The predicted cytoplasmic dt protein showed a high resemblance with flowering protein centroradialis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01135-1.

Health Insurance: Awareness, Utilization, and its Determinants among the Urban Poor in Delhi, India.

This study reports the awareness, access, and utilization of health insurance by the urban poor in Delhi, India. The study included 2998 households from 85 urban clusters spread across Delhi. The data were collected through a pretested, interviewer-administered questionnaire. Logistic regression was performed for determinants of health insurance possession. Only 19% knew about health insurance; 18% had health insurance (8% Employees State Insurance Scheme - ESIS - 8% Central Government Health Scheme - CGHS - 1.4%; Rashtriya Swasthya Bima Yojana (RSBY) - 9.4% of the eligible households). In case of health needs, 95% of CGHS, 71% ESIS beneficiaries, and 9.5% of RSBY beneficiaries utilized the schemes for episodic and chronic illnesses. For hospitalization needs, 54% of RSBY, 86% of ESIS, 100% CGHS utilized respective services. Residential area, migration period, possession of ration card, household size, and occupation of the head of the household were significantly associated with possession of RSBY. RSBY played a limited role in meeting the healthcare needs of the people, thus may not be capable of contributing significantly in the efforts of achieving equity in healthcare for the poor. Relatively, ESIS and CGHS served the healthcare needs of the beneficiaries better. Expansion of ESIS to the informal workers may be considered.

Correlation of altered expression of a long non-coding RNA, NEAT1, in peripheral blood mononuclear cells with dengue disease progression.

The association of long non-coding RNAs (lncRNAs) with dengue disease progression is currently unknown. Therefore, the present study aimed to identify lncRNAs in different categories of dengue patients and evaluate their association with dengue disease progression. Herein, we examined the expression profiles of lncRNAs and protein-coding genes between other febrile illness (OFI) and different grade of dengue patients through high-throughput RNA sequencing. We identified Nuclear Enriched Abundant Transcript 1 (NEAT1) as one of the differentially expressed lncRNAs (adjusted P ≤ 0.05 and log-fold change ≥ 2) and subsequently validated the expression by qRT-PCR. The co-expression analysis further revealed that NEAT1 and the coding gene IFI27 were highly co-expressed and negatively correlated with dengue severity. Using regression analysis, we observed that NEAT1 expression was significantly dependent on disease progression (Coefficient = -0.27750, SE Coefficient = 0.07145, and t = -3.88).Further, receiver operating characteristic (ROC) curve revealed that NEAT1 expression could discriminate DI from DS (sensitivity and specificity of 100% (95%CI: 85.69 - 97.22) and area under the curve (AUC) = 0.97). Overall, the results of this study offer the first experimental evidence demonstrating the correlation between lncRNAs and severe dengue phenotype. Monitoring NEAT1and IFI27 expression in PBMC may be useful in understanding dengue virus-induced disease progression.

Characterization of the occult hepatitis B virus variants circulating among the blood donors from eastern India.

A previous study from West Bengal documented very high rate of occult HBV infection (OBI) among the HBsAg negative blood donors. This study was aimed to characterize the OBI strains circulating among the blood donors and to estimate the risk associated with the prevailing viral variants/mutants. Blood samples from 2195 voluntary blood donors were included in the study. HBsAg, HBeAg, anti-HBc, and anti-HBs statuses of the samples were done by ELISA based detection. PCR amplification and sequencing were done to determine HBV genotypes, basal core promoter (BCP), and precore (Pre-C) mutations. Among the study samples, 268 were anti-HBc positive/HBsAg negative, among which 65 (24.25%) were HBV DNA positive. Phylogenetic analysis revealed the presence of HBV/D (87.23%), HBV/A (8.51%), and HBV/C (4.26%) (P < 0.0001). HBV/D3 (65.85%) was the significantly prevalent subgenotype over HBV/D2 (26.83%) and HBV/D1 (7.31%) (P = 0.0003). Considerable prevalence of differential BCP (1752C, 1753C, 1762T/1764A, 1753C+1762T/1764A, 1773C, and 1814C) and reverse transcriptase (rt) gene (rtI91L, rtL93P, rtS106C, rtR110G, rtN118T, rtS119T, rtY126H, rtG127W/R, rtC136R, and rtY158H) mutations was identified. Association of specific HBV subgenotypes with OBI was interesting and needs further study. Clinically relevant mutations were prevalent among the OBI strains which are of serious concern.

Characterization of treatment-naive HIV/HBV co-infected patients attending ART clinic of a tertiary healthcare centre in eastern India.

OBJECTIVE: The study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile. METHODS: Pool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance. RESULTS: The prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ≥20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p = <0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ≥2,000 IU/ml of which 37.0% had HBV DNA ≥20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients. CONCLUSION: The prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation.

Shift in the hepatitis B virus genotype distribution in the last decade among the HBV carriers from eastern India: possible effects on the disease status and HBV epidemiology.

In a previous study from eastern India, the prevalence of HBV/C has been increasing among the blood donors. In order to analyze whether there has been any shift in HBV genotype distributions in recent years, the HBV genotypes prevalent during the periods 2000-2002 (Group-I; n=176) and 2007-2009 (Group-II; n=203) were compared, with special attention to changes in the proportion of HBV/C. The rate of prevalence of the three HBV genotypes (A, C, and D; percent prevalence 19.9/21.6/58.5 in Group-I vs. 31.0/28.6/40.4 in Group-II) underwent significant changes with increases in HBV/A and HBV/C among the HBV carriers (0.002). Among the asymptomatic carriers, the prevalence of these two genotypes (P=0.021 for HBV/A and P=0.005 for HBV/C) was significantly high. A notable increase was also observed among the chronic liver disease cases. HBV/A increased significantly among the older age Groups (≥ 51 years), whereas the increase of HBV/C was significant among the younger age Groups (≤ 20 years). With the increase of HBV/A and HBV/C, the rates of basal core promoter double mutation (1762T/1764A) also increased considerably. Binary logistic regression analysis revealed that both HBV/A and 1762T/1764A mutations are predictors of chronic liver disease state over asymptomatic carrier state. Thus, this study highlights the possible influence of HBV genotype shift on the changing scenario of HBV epidemiology and disease in the population.

Association of Interleukin-1ß and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population.

BACKGROUND: Interleukin-1ß (IL-1ß) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection. OBJECTIVES: This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1ß (IL-1ß) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals. METHODS: DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1ß (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively. RESULTS: Among the study subjects, different IL-1ß (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1ß promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1ß -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1ß (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC. CONCLUSION: IL-1ß polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1ß polymorphisms with HBV-related hepatic complications.

Effect of smoking on semen quality, FSH, testosterone level, and CAG repeat length in androgen receptor gene of infertile men in an Indian city.

This study was conducted as part of an epidemiological survey of 126 nonsmokers and 178 smokers, showing primary infertility residing around Kolkata region of Eastern India. Their lifestyle history including smoking habits along with semen and blood were collected. The study examined the association of cigarette smoking with the risk of infertility, by determining the semen quality, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone levels, and androgen receptor (AR)-CAG repeat length in a group of smokers compared with a control group (non smokers). Based on conventional WHO criteria, lower sperm motility (P < 0.001) and increased sperm morphological defects (P < 0.0001) were associated with smoking habits. Binary logistic regression analysis for the effect of smoking status on sperm DNA integrity demonstrated significant positive correlation (p = 0.006). Serum FSH and LH levels were higher for smokers compared with non-smokers while the testosterone level decreased significantly with the increasing smoking habit. The mean length of CAG repeats in AR gene was significantly higher for smokers with low testosterone compared to non-smokers. The study suggested that smoking is associated with altered semen quality, endocrine hormonal status, and number of CAG repeats in the AR gene.

Differential pattern of pre-S mutations/deletions and its association with hepatitis B virus genotypes in Eastern India.

The presence of three different HBV genotypes (A, C and D) in Eastern India provided us a unique opportunity to study HBV pre-S mutants in these genotypes and subtypes among the same ethnic population. Furthermore, we also aimed to investigate the association of the HBV pre-S mutation with clinical outcome. Pre-S1-S2 and S gene was amplified and sequenced from 86 HBsAg positive study subjects with varying clinical manifestation. The genetic variability in the pre-S region (mutations) was studied with respect to different HBV genotypes, subtypes and different clinical categories. Six different types of HBV pre-S mutations were detected in 25 cases (29.07%), among which pre-S2 start codon mutation (28.0%) and pre-S2 deletion (24.0%) were most common. Pre-S mutation was highest in HBV/C (7/18; 38.89%) followed by HBV/A (9/27; 33.33%) and HBV/D (9/40; 22.50%). Pre-S1 deletion is common in HBV/D, whereas pre-S2 start codon mutation and pre-S2 deletions are frequent among HBV/A and HBV/C, respectively. Interestingly, in HBV/A and HBV/C the tendency of mutation/deletion increases from pre-S1 to pre-S2 region while in HBV/D the opposite tendency was observed. A significantly higher association of pre-S mutation (p=0.013) and pre-S2 deletion/ablation (p=0.016) was found among the HBeAg negative cases. Pre-S1 deletion and pre-S2 deletion were common among the ASC and CLD cases respectively, while pre-S2 start codon mutation was significantly associated with cirrhosis (p<0.05). The study underscores the association of types of pre-S mutations with particular HBV genotype and clinical outcome in the study population.

Variations in the functional domain of basal core promoter of hepatitis B virus among Eastern Indian patients with prevalence of genotypes A, C, and D among the same ethnic population.

Mutations in the basal core promoter (BCP) and precore (PC) regions are associated with persistent and intermittently high hepatitis B virus (HBV) replication in several patients. The variability in the functional domains of BCP and PC region of HBV and their association with disease progression and clinical outcome were assessed in Eastern India, an unique region where three HBV genotypes, A, D, and C are prevalent among the same ethnic group. PCR amplification and direct sequencing of BCP and PC region was done on sera obtained from 130 HBsAg positive subjects with different clinical presentations. Associations of the apparent risk factors with clinical advancement were evaluated by statistical methods including multiple logistic regression analyses (MLR). HBV genotype A was present in 33.08%, C in 25.38%, and D in 41.54% cases. Genotypes A and C were associated with higher rate of T1762/A1764 mutations than the most predominant genotype D. HBeAg negative state was associated with considerably higher rate of C1753 mutation. T1762/A1764 along with C1753 was common among cirrhosis and T1762/A1764 without C1753 was frequent among chronic liver disease cases. No significant association was found between A1896 point mutation and clinical status. Multivariate analysis revealed that T1762/A1764 double mutation, HBV/A, age ≥25 years, C1753 and A1899 were critical factors for clinical advancement while age ≥25 years and C1753 as significant predictor for cirrhosis in comparison with chronic liver disease. In conclusion, the analysis of the BCP variability may help in monitoring the progression towards advanced liver disease in Eastern Indian patients.

Carcinoid of the trachea in a young adult male responsive to chemo-radiation.

Carcinoid of the trachea is an extremely rare entity with very few cases reported in literature. The standard of treatment is complete surgical excision with limited role for chemotherapy and also a limited role for radiotherapy as this type of tumour has very low metastatic potential. We describe a case of a tracheal carcinoid which was surgically unresectable, but which showed excellent response to combined modality treatment with sequential multi-agent chemotherapy followed by radiotherapy with complete resolution of disease.

Proboscis lateralis: case report and overview.

We present a rare case of the congenital malformation of the nose in a 10-month-old baby.

Cemento-ossifying fibroma of the maxilla: a case report.

We report a case of very large ossifying fibroma of the maxilla in a 22-year-old male. It is a bony tumour of the maxilla of possibly odontogenic origin with aggressive behavior and high tendency for recurrence.

Objective acoustic analysis of voice improvement after phonosurgery.

OBJECTIVE: To evaluate voice improvement after phonosurgery by objective acoustic analysis. MATERIAL AND METHODS: This prospective study was conducted in Maulana Azad Medical college New Delhi from December 2002 to 2008. In this study 100 subjects were included comprising of all age groups and either sex. All these patients with organic voice disorder underwent speech analysis using VAUGMI speech analysis program before and after phonosurgery. RESULT: All the parameter of voice analysis were deranged before the treatment but after surgery all the parameters should improvement most significant change was seen in the jitter. CONCLUSION: After doing this study we found that the analysis of hoarse voice using various parameters of acoustic analysis like fundamental frequency, harmonics to noise ratio, jitter, shimmer, S/z ratio helped us in identifying the degree of hoarseness and the severity related to it. Some parameters like jitter and shimmer were able to detect the component of hoarseness in perceptually normal voice and thus patient was helped by doing surgery and voice therapy at the appropriate time.

Semen quality and age-specific changes: a study between two decades on 3,729 male partners of couples with normal sperm count and attending an andrology laboratory for infertility-related problems in an Indian city.

OBJECTIVE: To compare the semen quality and age-specific changes in men between the 1980s and 2000s. DESIGN: Prospective study. SETTING: Andrology laboratory, University of Calcutta, India. PATIENT(S): A semen sample was obtained from 3729 men presenting for infertility problems in two distinct decades, that is, between 1981-85 and 2000-2006. INTERVENTION(S): Subjects with sperm count >20 x 10(6)/mL without any extreme pathological disorders were selected. Samples having a major liquefaction problem were excluded. MAIN OUTCOME MEASURE(S): A standard World Health Organization procedure for semen analysis was performed that included assessment of volume, sperm concentration, and percentage motility. The motility parameters were further classified into forward progressive motility and nonprogressive motility. RESULT(S): The present large-scale study confirms a significant decline in the sperm motility parameters and seminal volume in the present decade. However, no change in overall sperm concentration was noted. A decline was seen in sperm motility with increasing age in both decades. CONCLUSION(S): There are significant changes in sperm motility and volume between the two decades, and the age-related changes in semen parameters are also different in the two decades.