Tuberculosis vaccine: pipeline approaches and future prospective

Tuberculosis (TB), despite anti-mycobacterial therapies and vaccine, is a deadly infectious disease with about 12 million incident cases worldwide. Existing Bacillus Calmette-Guérin (BCG) vaccine is unquestionably inexpensive, safe and effective against severe forms of childhood TB but appears to be limited in effectiveness against adult pulmonary disease in endemic areas. Genetic variation in the population is the major obstruction inhibiting validation of biomarkers for protective human immunity against TB. Since current TB cases are presenting new challenges with threats of HIV co-infection therefore various attempts at a global platform are being made to develop a new modified vaccine against it. Consequently, Modified Vaccinia Ankara virus (MVA) vectored MPT64 & Ag85A delivery and polyvalent DNA vaccine, expressing an ESAT6–Ag85B fusion protein etc. are preclinically tested for boosted immune effects. However, better vaccine approaches still need to be developed against M. tuberculosis which can be unbeaten in most infected areas

A comparative study of morbidity pattern among rural and urban postmenopausal women of Allahabad, Uttar Pradesh, India

Background: Menopause is an inevitable reproductive phase during midlife when various physical and mental changes may impair the quality of life of women. Middle-aged women may experience a wide range of physical and psychological symptoms. Decrease in the production of estrogen leads to the premenopausal symptoms of hot flushes, insomnia and mood changes, as well as post-menopausal osteoporosis and vaginal atrophy, leading to decrease in quality of life.Methods: Community based cross-sectional study. Door to door survey was conducted among women who had attained menopause for more than 1 year, in rural and urban area of Allahabad. Multistage random sampling was done. 400 postmenopausal women, 200 each from rural and urban area were selected. A pre-tested structured questionnaire was used for data collection.Results: Majority were in the age group of 50-60 years followed by 60-70 years. Majority of women were having a parity of 3. Vasomotor symptoms were experienced by 34.5% and 39.5% rural and urban women respectively. Out of total post-menopausal women who reported genitourinary complaints, the most commonly reported complaint was stress incontinence i.e. 10.5% and 8.5% respectively in rural and urban communities followed by increased urinary frequency i.e. 9% and 7.5% respectively in rural and urban areas. Vaginal dryness was reported by 2.5% of rural women and 6% of urban women. Vaginal discharge was reported by 7% of rural and 4% of urban women. Uterine Prolapse was reported by 6% of rural women and 3.5% of urban women.Conclusions: The study shows that postmenopausal women in India suffer from various vasomotor, physical as well as psychiatric problems related to menopausal hormonal changes with varied frequencies. There is a need to address their problem and establish health care centers for them. Postmenopausal women should be sensitized for availing the health facilities for their health problems by information education and communication (IEC) and behaviour change communication (BCC). Family support should be ensured by creating awareness in community. Awareness regarding menopause and problems among women related to it need to be improved. Health workers, ASHA, Aanganwadi workers can help women to understand about the menopausal symptoms, if they are given adequate training

PHARMACOGNOSTICAL AND PHARMACOLOGICAL EVALUATION OF CRINUM LATIFOLIUM L.

Objective: Pharmacognostical study along with the development of a quantitative HPTLC method for Crinum latifolium and evaluation of its traditional claims. Methods: Quantification of three marker compounds oleanolic acid, linoleic acid, and lupeol was done through HPTLC. In vitro antioxidant activity was determined by six different models, namely total phenolic and total flavonoid content, DPPH radical scavenging assay, ferric reducing power, antioxidant capacity and hydroxyl radical scavenging assay. In vitro antidiabetic activity was evaluated by α-amylase inhibition assay based on starch iodine and DNS method. Results: The content of oleanolic acid, linoleic acid, and lupeol were found to be higher in aerial parts like 0.015%, 0.048%, and 0.028% respectively, while in root extract 0.006%, 0.027% and 0.025% respectively on a dry weight basis. Free radical scavenging activity was done by DPPH assay, showing the IC50 value of 410±1.105 µg/ml in roots and 441.95±1.788 in aerial parts. In vitro antidiabetic potential of both the parts were assessed by starch iodine color assay and DNS method of alpha-amylase inhibition model. In 3,5 DNS assay, IC50 of extract from aerial parts was 282.21±2.151µg/ml whereas in root extract it was 193.33±2.45µg/ml. Iodine-starch assay of C. latifolium (aerial part) shown the IC50 value of 340.81±0.49 µg/ml and C. latifolium (root) of 74.64±1.28 µg/ml. Conclusion: The results indicate that the aerial parts of the plant possess more antidiabetic potential in comparison to the root. Thus, the aerial part can be used to get better results as a drug and roots can be used as an alternative

Cost-effectiveness of population-based screening for oral cancer in India: an economic modelling study

Background: Oral cancer screening reduces mortality associated with oral cancer. The current study evaluated the cost-effectiveness of commonly used screening techniques, namely conventional oral examination (COE), toluidine blue staining (TBS), oral cytology (OC), and light-based detection (LBD) in the Indian scenario. Methods: The study used a Markov modelling approach to estimate the cost and health outcomes of four different approaches (COE, TBS, OC, and LBD) for screening oral cancer over time from a societal perspective. The discount rate was assumed as 3%. The outcomes estimated were oral cancer incident cases, deaths averted, and quality-adjusted life years (QALYs). To address the high burden of risk factors (tobacco and/or alcohol) in India, two Markov models were developed: Model A adopted a mass-screening strategy, whereas Model B adopted a high-risk screening strategy versus no screening. Probabilistic sensitivity analysis (PSA) was undertaken to address any parameter uncertainty. Findings: Mass-screening using LBD at three years had the least incident cases (3271.68) and averted the maximum number of oral cancer deaths (459.76). High-risk screening using COE at ten years interval incurred the least lifetime cost of 2,292,816.21 US$(182,794,468.26 INR). The high-risk strategies (US$/QALY), namely COE 5 years (−29.21), COE 10 years (−90.68), TBS 10 years (−60.54), and LBD 10 years (−13.51), were dominant over no-screening. Interpretation: The most cost-saving approach was the conventional oral examination at an interval of 10 years for oral screening in high-risk populations above 30 years of age. Funding: Department of Health Research, Ministry of Health & Family Welfare, Government of India

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients

Persistencia de malezas gramíneas en cultivos de trigo del sudeste bonaerense

En la presente tesis se estudió la persistencia de especies poáceas en cultivos de trigo del sudeste de Buenos Aires. En dicha región, Avena fatua L. y Lolium multiflorum Lam. son las malezas poáceas más importantes, tanto por la dificultad de control como por sus efectos competitivos sobre el cultivo. A los efectos de cuantificar la persistencia de dichas especies, se estudió la composición de la comunidad de malezas en dos momentos del ciclo: preaplicación de herbicidas y precosecha. Individuos de ambas malezas fueron registrados en ambos momentos como consecuencia de “escapes” al control realizado con herbicidas, siendo A. fatua más constante que L. mutiflorum. Posteriormente, se estudiaron los procesos que definen la persistencia de ambas malezas. Los resultados obtenidos indican que el ajuste del momento de emergencia es jerárquicamente el factor más importante para explicar la persistencia de A. fatua. Se demostró que los modelos de germinación son diferentes según las semillas provengan de un lote agrícola o de una condición de no cultivo, siendo estas diferencias de naturaleza genética. Por otro lado, la variabilidad en la supervivencia a los herbicidas es el factor que mejor explica la persistencia de L. multiflorum, habiéndose documentado resistencia cruzada a los herbicidas inhibidores de la ALS, pyroxsulam, imazamox y flucarbazone, sin antecedentes previos en la región. Los índices de resistencia encontrados presentan variación con la temperatura ambiente en post-aplicación del herbicida, habiéndose registrado mayor resistencia con mayor temperatura. Además, se comprobó que los individuos resistentes presentan menor tiempo a floración que los susceptibles. Tal atributo puede significar una ventaja demográfica para dichas poblaciones. Queda así demostrada la persistencia de A. fatua y L. multiflorum durante el ciclo del cultivo más allá de las prácticas de control realizadas y la participación de dos procesos demográficos distintos (establecimiento y supervivencia) en dicha persistencia

Implication of Solarization against Soil -borne fusaria in leguminous crop fields in Kalli paschim village in Lucknow, India: A Tropical Country

ABSTRACT Soil solarisation is a technique to trap sun's energy helps to increase the temperature of the soil .This higher temperature is unsuitable for most of the plant pathogens results decreased in their population. It's a very beneficial technique for management of pathogen microbes in tropical countries where sunlight is available for a long period in a day time. Soil solarisation also helps to increases the productivity of soil both by suppressing the pathogens as well as by increasing the metabolic rate of soil materials, which helps to enhance the fertility of the soil. This procedure is also enhancing the bulk and bustle of antagonistic microbes. The purpose of present study is to test the effect of soil solarization on population dynamics of two pathogenic soil fusaria i.e. Fusarium oxysporum f.sp.ciceri and fusarium udum causing wilt in chickpea and pigeonpea crops. All treatment comprises treated plots and untreated (control) plots at different depth i.e. 5, 10 and 15 cm on 7, 14 and 21 st days of experiment. It is found that in solarized plots the population of pathogens significantly reduced in compared to control plot. Significant increase in temperature is found in solarized plots in comparison to control with increase in days of experiment

Ultrafine Particles of Diesel Exhaust Induces Cytochrome P450 1A1 Mediated Oxidative Stress and DNA Damage in Cultured Blood and Lung Cells

Attempts were made to investigate the role of cytochrome P450 1A1 (CYP1A1) on similarities in the generation of reactive oxygen species (ROS) and DNA damage in IM9, a human B lymphoblastic cell line with A549, the human lung adenocarcinoma epithelial cell line on exposure of diesel exhaust particles (DEP). A suspension of ultrafine particles (< 0.2 μM) of DEP (1mg/ml) in DMEM-F12 medium, at a concentration range of 1-100 μg/ml, was added to the cells for 6-48h. Expression studies revealed that DEP induced similar increase in the expression of CYP1A1, generation of ROS and DNA damage in both the cells. Pre-incubation with 3-methylcholanthrene (MC), a CYP1A1 inducer resulted in higher magnitude of induction of CYP1A1, ROS and DNA damage. This synergistic effect was lowered when α-naphthoflavone (α-NF), an inhibitor of CYP1A1 catalysed reactions, was added to these cells. Though the magnitude of alterations was lower in IM9 cells when compared to A549 cells, similarities in the alterations in blood and lungs cells has further suggested that blood lymphocytes can be used as a surrogate to monitor toxicity of vehicular emissions