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Advancement in technology led to development of live attenuated Salmonella typhi Ty21a as enteric vector for expression of foreign proteins. Such vector platform is inevitable for development of vaccine candidate against human papilloma virus (HPV), the etiological agent of cervical cancer with high prevalence in developing nations. The high risk HPVs like type 16 and 18 contributes to 70% of cervical cancer, hence Indian Immunologicals Limited (IIL), Hyderabad, India developed a recombinant HPV vaccine by introducing HPV 16 and 18 L1 protein coding genes into attenuated S. typhi Ty21a vector. Being a genetically engineered enteric vector vaccine, it would be less expensive, with an ease of oral administration, instead of injectable that needs trained personale, is an added advantage for low socioeconomic setup compared to existing HPV vaccines. Establishing the nonclinical efficacy and safety/toxicity as per the national/international regulatory guidelines has become major constrain for such recombinant S. typhi HPV (rSt.HPV) vaccine. Since, the intended clinical mode of rSt.HPV is through oral route, whereas the live attenuated S. typhi Ty21a doesn't colonize in gut of laboratory animals to be used for nonclinical experiments. Hence, an alternate and unconventional method of ‘intranasal drug testing’, was followed for nonclinical efficacy and toxicity evaluations. An array of parameters specified by regulatory agencies were investigated in mice, rat and rabbits administered with rSt.HPV through, intra-peritoneal, intranasal and oral routes, the intended clinical route.•Current unconventional and innovative nonclinical testing procedures helps in exploring the alternate methods by pharmacologist/toxicologist.•Ultimately, such new drugs developed through technology must serve the humankind justifying the guidelines of regulatory agencies., Graphical abstract Image, graphical abstract

AIM The human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and 18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins. METHODOLOGY The acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days. RESULTS No abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P

Azoles are prominent scaffolds in the pharmaceutical arena. In fact, medicinal properties of azole and benzazole containing compounds include anticancer, antimicrobial and antioxidant. Some of the drugs Inthomycin C, Oxaprozin, Tiazofurin, Dacarbazine, Tipifarnib, Albendazole, Febendazole, Omeprazole possess azole/benzazole moiety. Realizing the importance of azoles and benzazoles, it is planned to conjugate these two ligands as heteroaryl substituted urea derivatives and to study their antimicrobial activity. The results pertaining to these aspects will be discussed. © 2020 Author(s). The authors K. Narendra Babu and V. Padmavathi are grateful to CSIR (Council of Scientific and Industrial Research), New Delhi for financial assistance under major research project.

MRKH (Mayer Rokitansky Kuster Hauser) syndrome is a congenital abnormality seen in one out of 5,000 women characterized by the agenesis of the vagina, cervix, and uterus. It is also associated with kidney, bone and hearing difficulties. The ovaries are present with a normal function similar to that of a healthy reproductive woman’s by producing eggs and female hormones. Chromosomes are the normal 46xx female karyotype. We report this rare syndrome in a 26–year-old female where she had presented with complaints of absence of uterus with the absence of left kidney. She didn’t attain menarchy, secondary sexual characters are well developed. Small right ovarian follicular cyst with a rim of ovarian tissue was observed. She had undergone vaginoplasty.

This study evaluated the persistence of heavy metals, cadmium (Cd), lead (Pb) and mercury (Hg) in surficial marine sediments and their relationship with textural characteristics. Furthermore, heavy metal distribution was studied against organic carbon concentration within the sediments. Our results suggest that Cochin estuary is highly polluted in the case of all heavy metals (Pb of 29.48± 4.37µg/g, Cd of 0.21± 0.17µg/g and Hg of 0.17± 0.15µg/g). All the studied trace elements showed negative correlation with sand particles. However , significant positive correlations were observed between lead and mercury with silt and organic carbon (P

Objective To explore the effect of letrozole as an ovulation inducing agent on oocyte and embryo quality in mice model. Design Prospective study. Setting Institute of Reproductive Medicine, Kolkata, India. Animal(s) Sixty-nine sexually mature female Swiss Albino mice 6–7 weeks old. Intervention(s) Metaphase II (MII) oocytes from two groups of mice, one group injected with letrozole and the other with rFSH. Main Outcome Measure(s) Number of MII oocytes, number of oocytes with meiotic spindle (MS), different angles of MS relative to the polar body (PB), spindle characteristics, and fertilization outcome. Result(s) The MS was present in 84% and 71.2% of the oocytes in the letrozole and rFSH group, respectively. In the letrozole group, 73% of the oocytes had a 0° spindle position compared with 35.7% in the rFSH group. With letrozole, 19% of the oocytes had 0° > MS 90°, compared with 46.1% oocytes with 0° > MS 90° with rFSH. Mean spindle area retardance, spindle dimensions, and 4–8-cell embryo formation rate were significantly higher with letrozole compared with rFSH. Two-cell and blastocyst formation rates were similar in both groups. Conclusion(s) Robust birefringent spindles were obtained in mice on superovulation with letrozole. Letrozole does not appear to increase the risk of spindle assembly and preimplantation developmental arrest in mouse oocytes.

Ashtamudi estuary, situated on the southwest coast of India, is enormously affected by anthropogenic interventions. Physicochemical quality of water and sedimentological features of the estuary are evaluated during monsoon and nonmonsoon seasons to elucidate its quality variations and to link the same with existing environmental scenario. The whole data has been factorized using principal component analysis for extracting the total variability and linear relationships existing among a set of different physicochemical parameters of the backwater system. In PCA, high loadings were obtained for conductivity, salinity, fluoride, calcium, magnesium, sulfate, boron, and pH. The results were revealed that all the physicochemical processes depend upon seasonal fluctuation of freshwater input and seawater intrusion. Wide spatial concentration fluctuations of organic carbon and iron in bottom sediment have been noticed and both constituents reveal good correlation with sediment texture. The results showed high deterioration of the physicochemical quality of water during nonmonsoon season with respect to monsoon season.

Probiotic supplementation during critical windows of gestation might have a significant influence on the infant’s immune phenotype. Swiss albino mice (F0 generation) aged 31 days were supplemented orally with probiotic Lactobacillus rhamnosus GG (LGG); and the supplementation was continued throughout mating, gestation and lactation. The pups (F1 generation) born to them were separated post weaning and received either the same probiotic supplementation as their mothers or were denied supplementation postnatally. Neutrophil phagocytic ability, splenocyte proliferation, immunoglobulins and cytokines were determined in both F0 and F1 pups. In addition, antibody response against hepatitis-B surface antigen (HBsAg) was determined in F1 pups. Probiotic supplementation had no effect on the neutrophil phagocytic ability and splenocyte proliferation index. The serum immunoglobulin G (IgG) and secretory IgA (s-IgA) among the probiotic supplemented group of F0 generation were significantly (P

This paper suggests a structure for possibility management utilizing smart loads that are acknowledged through the rising standard of the IoT (Internet of things). LSEs (load-serving substances), operators of this system, and the end-users with smart home management frameworks, which mechanically control the adaptable loads are involved in this framework. The operator of the framework uses a profcient linear equation solver to quickly compute the load reduction required at every bus to release congested lines after a possibility. In this reduction request, a power allowance is calculated by LSE, for each of its end-user to increase the aggregate client utility.

This article presents application of non dominated sorting based gravitational search algorithm (NSGSA) for solving optimal power flow (OPF) problems with economic and environment objectives. Fast elitist non-dominated sorting and crowding distance have been used to locate and manage the Pareto optimal front. The proposed method is tested and implemented on standard IEEE 30-bus test power system, with different objectives, that reflect the minimization of total quadratic fuel cost, piecewise quadratic fuel cost, fuel cost with valve point loading effect of generators and emission cost. The numerical results have been compared with other recently developed algorithms to reveal the tangible superiority of the proposed method for solving the OPF problems.

Application of non dominated sorting multi objective gravitational search algorithm (NSMOGSA) for solution of different optimal power flow (OPF) problem is presented in this article. NSMOGSA is an extension of the gravitational search algorithm (GSA), where the gravitational acceleration is updated using non-dominated sorting concept. A mixture of sign and reordering mutations are also proposed in to reduce the chance of trapping in local optima. The proposed method is employed for optimal adjustments of the power system control variables which involve both continuous and discrete variables of the OPF problem. To show the effectiveness of the proposed algorithm, it has been tested on a standard IEEE 30-bus system with two different individual objectives that reflect total emission cost minimization and fuel cost minimization. The performance of NSMOGSA is compared with the results found by other meta-heuristic techniques reported in the recent literature to demonstrate the tangible superiority of the proposed method.

This study evaluated the relationship between the traditional indicators of faecal pollution, total coliforms (TC), faecal coliforms (FC) and Faecalstreptococci (FS), and the presence of few potentially pathogenic enteric bacteria, Vibrio cholerae (VC), Vibrio parahaemolyticus (VP), Shigella spp. (SH) and Salmonella spp. (SL) in coastal sea water. The distributional statuses of these bacteria were also studied along the Southern Kerala coast. Cluster analyses were done to identify similar groups of indicator as well as enteric pathogenic bacteria. Kochi was found to be highly polluted with enteric pathogens and indicator bacteria (TC of 4700, VC of 820, FC of 920 and FS of 410 CFU ml(-1)). Percentage incidence of VC (97.42%) was comparatively higher than the traditional indicator bacteria (TC 95.04%, FC of 63.64% and FS of 47.64%). VC found to be rather stable and showed significant relationship with all the traditional indicator bacteria (R20.370), suggests that both quantitatively and qualitatively the abundance of Vibrio cholerae can determine faecal pollution, could be used as a faecal pollution indicator bacterium, especially in the marine environment where traditional indicator bacteria failed to survive. It would be advisable to always perform the detection of SH and VP beside the traditional indicators as no significant relationship (R2or =0.076, p0.05) exists among them.

Miscellaneous statistical approaches were applied to illustrate the influence exerted by different zooplankton groups on the survival and distributional status of autochthonous Vibrio cholerae in two diverse marine environments, Veli and Kochi, former with low nutrient loading and later with high nutrient loading. The data set has been factorised using principal component analysis (PCA) for extracting linear relationships existing among a set of variables. Box plots were derived from the PCA data and were graphically represented. Vibrio cholerae (VC) showed strong positive correlation to zooplanktons especially with crustacean copepods under low nutrient conditions which confirmed a clear association between VC and zooplanktons for its surveillance and distribution under low nutrient concentration, while under high nutrient loading VC rely only on the available nutrients.

Spatial and temporal variations in concentration of dissolved metals viz. Copper (Cu), Lead (Pb), Chromium (Cr), Nickel (Ni), Zinc (Zn), Cadmium (Cd) and Mercury (Hg) in surface waters of southwest coast of India were studied. Concentrations of metals showed an aberration both temporally and spatially. Seasonal average concentrations of the analyzed metals followed the order Zn > Ni > Cu > Pb > Cd > Cr > Hg. The degree of contamination due to metal was determined by comparison with coastal water quality criteria. It established enrichment of Cu, Zn, Ni and Hg due to anthropogenic influence along southwest coast of India.

Autonomous robotic navigation and mapping have been of tremendous interest during the last decade. While several approaches have been presented, little is known about performing these tasks when constraints are placed on the processing resources and sensors. This paper studies the effectiveness in performing a few high level tasks when a mobile robot is equipped merely with a low-end microcontroller and four ultrasonic sensors. It is shown that the data memory on the microcontroller plays a crucial role in map construction of indoor environment. Four sensors are shown to be adequate for good quality map construction and for following a wall reasonably well. Experiments on map construction and wall following in an indoor environment using a mobile robot equipped with merely an Atmel 89C52 (and no external memory) are presented.