Cross-population genetic analysis revealed genetic variation and selection in the Ovar-DRB1 gene of Indian sheep breeds.

In sheep, MHC variability is studied widely to explore disease association. The aim of the current study was to explore the genetic diversity of Ovar-DRB diversity across sheep breeds of India. Here, Ovar-DRB1 locus was studied across 20 sheep breeds. DRB1 was amplified (301 bp) and sequenced using a PCR-sequence-based typing approach. Results revealed a high degree of heterozygosity across breeds (mean: 73.99%). Overall mean distance for DRB1 was highest in Sangamneri (0.18) and lowest in Madgyal sheep (0.10). There was a higher rate of transition, across breeds. Further, 39 alleles were isolated in different breeds, out of which 10 were new. To allow easy access and use of the immune-polymorphic database, an online database management system was launched (http://www.mhcdbms.in/). Nucleotide content across breeds for the DRB1 region revealed the richness of GC content (59.26%). Wu-Kabat index revealed vast genetic variation across peptide binding sites (PBS) of DRB1. Residues 6, 66, 69, 52, and 81, were polymorphic showing utility for antigen presentation. All breeds were under positive selection for DRB1 locus (dN > dS). Study revealed the importance of DRB locus diversity for beta chain specifically at PBS across sheep breeds of the Indian subcontinent and presented evidence of positive selection for DRB owing to its evolutionary significance.

Impact of airborne total suspended particles (TSP) and fine particulate matter (PM2.5 )-induced developmental toxicity in zebrafish (Danio rerio) embryos.

Airborne total suspended particles (TSP) and particulate matter (PM2.5 ) threaten global health and their potential impact on cardiovascular and respiratory diseases are extensively studied. Recent studies attest premature deaths, low birth weight, and congenital anomalies in the fetus of pregnant women exposed to air pollution. In this regard, only few studies have explored the effects of TSP and PM2.5 on cardiovascular and cerebrovascular development. As both TSP and PM2.5 differ in size and composition, this study is attempted to assess the variability in toxicity effects between TSP and PM2.5 on the development of cardiovascular and cerebrovascular systems and the underlying mechanisms in a zebrafish model. To explore the potential toxic effects of TSP and PM2.5 , zebrafish embryos/larvae were exposed to 25, 50, 100, 200, and 400 µg/ml of TSP and PM2.5 from 24 to 120 hpf (hours post-fertilization). Both TSP and PM2.5 exposure increased the rate of mortality, malformations, and oxidative stress, whereas locomotor behavior, heart rate, blood flow velocity, development of cardiovasculature and neurovasculature, and dopaminergic neurons were reduced. The expression of genes involved in endoplasmic reticulum stress (ERS), Wnt signaling, and central nervous system (CNS) development were altered in a dose- and time-dependent manner. This study provides evidence for acute exposure to TSP and PM2.5 -induced cardiovascular and neurodevelopmental toxicity, attributed to enhanced oxidative stress and aberrant gene expression. Comparatively, the effects of PM2.5 were more pronounced than TSP.

Impact of the Diabetes Inpatient Care and Education (DICE) project on length of stay and mortality.

AIM: To determine whether the Diabetes Inpatient Care and Education (DICE) programme, a whole-systems approach to managing inpatient diabetes, reduces length of stay, in-hospital mortality and readmissions. RESEARCH DESIGN AND METHODS: Diabetes Inpatient Care and Education initiatives included identification of all diabetes admissions, a novel DICE care-pathway, an online system for prioritizing referrals, use of web-linked glucose meters, an enhanced diabetes team, and novel diabetes training for doctors. Patient administration system data were extracted for people admitted to Ipswich Hospital from January 2008 to June 2016. Logistic regression was used to compare binary outcomes (mortality, 30-day readmissions) 6 months before and after the intervention; generalized estimating equations were used to compare lengths of stay. Interrupted time series analysis was performed over the full 7.5-year period to account for secular trends. RESULTS: Before-and-after analysis revealed a significant reduction in lengths of stay for people with and without diabetes: relative ratios 0.89 (95% CI 0.83, 0.97) and 0.93 (95% CI 0.90, 0.96), respectively; however, in interrupted time series analysis the change in long-term trend for length of stay following the intervention was significant only for people with diabetes (P=0.017 vs P=0.48). Odds ratios for mortality were 0.63 (0.48, 0.82) and 0.81 (0.70, 0.93) in people with and without diabetes, respectively; however, the change in trend was not significant in people with diabetes, while there was an apparent increase in those without diabetes. There was no significant change in 30-day readmissions, but interrupted time series analysis showed a rising trend in both groups. CONCLUSION: The DICE programme was associated with a shorter length of stay in inpatients with diabetes beyond that observed in people without diabetes.

Infections among Contacts of Patients with Nipah Virus, India.

We conducted a serosurvey of 155 healthcare workers and 124 household and community members who had close contact with 18 patients who had laboratory-confirmed Nipah virus infections in Kerala, India. We detected 3 subclinical infections; 2 persons had IgM and IgG and 1 only IgM against Nipah virus.

Inhibition of adhesion-specific genes by Solidago virgaurea extract causes loss of Candida albicans biofilm integrity.

AIMS: Candida albicans biofilms are commonly associated with severe oral infections. We previously discovered that a crude extract from the Solidago virgaurea plant (SV extract) was a potent inhibitor of C. albicans biofilm formation. Here, we further investigate the mechanisms underlying C. albicans biofilm inhibition by the SV extract. METHODS AND RESULTS: The SV extract was shown to inhibit laboratory and clinical C. albicans isolates adherence and hyphal transition on inert support and epithelial human cells, without affecting viability and growth of planktonic yeasts. Interestingly, RT-PCR-based experiments demonstrated that some key genes involved in adhesion and hyphal morphological switch (e.g. Hwp1p, Ece1p, Als3p) were strongly down-regulated by the SV extract. Moreover, antimicrobial synergy testing (checkerboard assay) demonstrated that antifungal effects of miconazole, nystatin or a common antiseptic mouthwash were synergistically improved when used in combination with the SV extract. CONCLUSIONS: The SV extract prevents C. albicans biofilm formation through direct inhibition of key adherence and hyphae-associated genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilm is considered as a key virulence factor of C. albicans infection. Our discovery of an inhibitor specifically acting on genes involved in biofilm formation paves the way for the future development of a new class of antifungal product.

Characterization and toxicology evaluation of zirconium oxide nanoparticles on the embryonic development of zebrafish, Danio rerio.

Zirconia oxide nanoparticles (ZrO2NPs) are known to be one of the neutral bioceramic metal compounds that has been widely used for their beneficial applications in many biomedical areas, in dental implants, bone joint replacements, drug delivery vehicles, and in various industrial applications. To study the effects of ZrO2NPs on zebrafish model, we used early life stages of the zebrafish (Danio rerio) to examine such effects on embryonic development in this species. ZrO2NPs were synthesized by the sol-gel method, size about 15-20 nm and characterized by SEM, EDX, XRD, FTIR, UV-Vis Spectra. In this study, zebrafish embryos were treated with ZrO2NPs 0.5, 1, 2, 3, 4, or 5 µg of nanoparticles/ml during 24-96 hour post fertilization (hpf). The results showed that ≥0.5-1 µg/ml of ZrO2NPs instigated developmental acute toxicity in these embryos, causing mortality, hatching delay, and malformation. ZrO2NPs exposure induced axis bent, tail bent, spinal cord curvature, yolk-sac, and pericardial edema. A typical phenotype was observed as an unhatched dead embryo at ≥1 µg/ml of ZrO2NPs exposure. This study is one of the first reports on developmental toxicity of zebrafish embryos caused by zirconium oxide nanoparticles in aquatic environments. Our results show that exposure of zirconium oxide nanoparticles is more toxic to embryonic zebrafish at lower concentrations. The results will contribute to the current understanding of the potential biomedical toxicological effects of nanoparticles and support the safety evaluation and synthesis of Zirconia oxide nanoparticles.

A novel combination of silane-coated silica colloid with hybrid RNA extraction protocol and RNA enrichment for downstream applications of spermatozoal RNA.

Spermatozoa are specialised cells with low RNA content as compared to somatic cells. The suitable sperm RNA extraction and enrichment protocols for downstream applications are available for human, cattle, stallion and mouse but not for buffalo spermatozoa. Therefore, the present work was conducted to find out suitable colloidal solution for sperm purification and appropriate protocol for sperm RNA extraction and enrichment/amplification of RNA. For purification, we used PVP-coated silica colloidal solution (PVP-Si), silane-coated silica colloidal solution (Silane-Si) and iodixanol. Sperm recovery rate, total sperm motility and progressive sperm motility were significantly improved after separation by Silane-Si and iodixanol compared to PVA-Si method. The combined guanidinium thiocyanate-phenol-chloroform (GTPC) with silica matrix (SM)-based RNA extraction yielded more quantity of RNA in compared to individual method. The hybrid of SM and GTPC into a single protocol yielded 360-450 ng RNA from 30 million buffalo spermatozoa. For the first time, we adopted new way to enrich sperm RNA that increased the RNA concentration 4-5 times that was sufficient for downstream applications. The linear amplification of sperm RNA increased RNA concentration around 27-45 times. In summary, Silane-Si colloid for sperm separation, hybrid SM and GTPC protocol for sperm RNA extraction followed by enrichment or amplification of RNA was found suitable for high-throughput analyses of buffalo sperm RNA.

Strain-specific variation in plant growth promoting volatile organic compounds production by five different Pseudomonas spp. as confirmed by response of Vigna radiata seedlings.

AIM: Analysis of a blend of volatile organic compounds (VOCs) released by Pseudomonas spp. with growth-promoting effect in Vigna radiata seedlings. METHODS AND RESULTS: Plant growth-promoting activity of VOCs produced by five different Pseudomonas spp. was investigated by I-plate technique. VOCs produced by different organisms were extracted by various solvents (methanol, ethyl acetate, hexane and butanol) and were identified by gas chromatography-mass spectrometric analysis. The major VOCs identified were undecane, nonadecane, hexacosane, tetradecane, heptacosane, pentadecane, dodecane and tetratetracontane. The cultural conditions for the production of VOCs with plant growth enhancement effect were optimized and further confirmed using pure pentadecane as a candidate VOC. CONCLUSIONS: The study provides insight into plant beneficial effect of VOCs produced by Pseudomonas spp. Remarkable modulation in the production of VOCs with plant growth-promoting effect by rhizobacteria was found to be dependent on the bacterial strain and its concentration. SIGNIFICANCE AND IMPACT OF THE STUDY: The study describes the requirement to consider bacterial VOC production also for preparing plant probiotic formulations. As VOCs are least considered for preparation of commercial plant growth-promoting rhizobacterial strain formulation, the results of the study is highly significant.

Polymorphism of growth hormone receptor (GHR) gene in Nilagiri sheep.

The allelic variation in the regulatory sequence of growth hormone receptor (GHR) gene influences the growth traits of sheep. A study was carried out to find out the polymorphisms associated with exon 10 of GHR gene and its association with growth traits of Nilagiri sheep. The blood samples were collected from Nilagiri sheep (n = 103) reared at Sheep Breeding Research Station, Sandynallah, Tamil Nadu, India. DNA was isolated using the phenol-chloroform extraction procedure and eight samples having amplified product of part of exon 10 (895 bp) sequenced. The results indicated transitions of nucleotide G>A at loci G177624A and G177878A. The genotyping frequencies estimated using the tetra-primer amplification refractory mutation system-PCR for GG, GA and AA were 0.262, 0.544 and 0.194, and 0.349, 0.505 and 0.146, respectively. The estimated allele frequencies of G and A nucleotides were 0.5340 and 0.4660, and 0.6015 and 0.3985, respectively, at loci G177624A and G177878A. The effects of both the mutations on growth-related traits viz., birth, weaning (3 months) 6, 9 and 12 months weight in Nilagiri sheep were found to be non-significant. This can be a novel approach to assess growth of sheep using the mutation in GHR gene. Thus, this approach can be useful for further investigation as a molecular marker associated with genetic improvement.

Impact of the Diabetes Inpatient Care and Education (DICE) project and the DICE Care Pathway on patient outcomes and trainee doctor's knowledge and confidence.

AIM: To evaluate the impact of the Diabetes Inpatient Care and Education project and a comprehensive diabetes care pathway, the Diabetes Inpatient Care and Education Care Pathway, on patient outcomes and on the knowledge and confidence of trainee doctors. METHODS: The effect on patient outcomes was evaluated by comparing the National Diabetes Inpatient Audit data before (2012) and after (2013) implementing the Diabetes Inpatient Care and Education project. The impact on trainee doctors was evaluated using the Modified Kirkpatrick model. Just before the project began and again 3 months later, trainee doctors were surveyed to assess their knowledge and confidence in inpatient diabetes care. RESULTS: Patient harm was found to have been reduced significantly when National Diabetes Inpatient Audit data for 2012 and 2013 were compared. Severe hypoglycaemia decreased from 15.4 to 9.7%, medication errors from 56.9 to 21.1% and insulin errors from 31 to 7%. Across the 96 trainee doctors surveyed, the mean (sd) knowledge and confidence scores increased significantly (P < 0.001 for both) from 57.1 (16.8) and 61.8 (14.9) to 68.4 (13.3) and 74.3 (11.7), respectively. CONCLUSION: The Diabetes Inpatient Care and Education project and the Diabetes Inpatient Care and Education Care Pathway improved patient outcomes and the knowledge and confidence of trainee doctors in this hospital. The impact of a similar project in other hospitals needs to be evaluated.

Impact on prevalence of intestinal helminth infection in school children administered with seven annual rounds of diethyl carbamazine (DEC) with albendazole.

BACKGROUND & OBJECTIVES: One third of the world's population is infected with one or more of the most common soil-transmitted helminths (STH). Albendazole (ALB) is being administered with diethyl carbamazine (DEC) in filariasis endemic areas to eliminate lymphatic filariasis (LF) and helminth infections. In this study, the cumulative impact of seven annual rounds of mass drug administrations (MDA) of DEC and ALB on STH infection in school children in selected villages in southern India was determined. METHODS: During 2001-2010, seven MDAs were implemented by the Tamil Nadu s0 tate h0 ealth d0 epartment, India. LF and STH infections were monitored in school children from 18 villages of the two treatment arms (viz, DEC alone and DEC+ALB). Kato-Katz cellophane quantitative thick smear technique was employed to estimate STH infections at three weeks, six months and one year post MDA. RESULTS: Prior to treatment, an overall STH prevalence was 60 per cent. After each MDA, infection markedly reduced at three weeks post-treatment in both the arms. The prevalence increased at six months period, which was maintained up to one year. After seven rounds of MDA, the infection reduced from 60.44 to 12.48 per cent in DEC+ALB arm; while the reduction was negligible in DEC alone arm (58.77 to 52.70%). INTERPRETATION & CONCLUSIONS: Seven rounds of MDA with DEC+ALB reduced the infection load significantly, and further sustained low level of infection for 10 years. However, complete parasite elimination could not be achieved. To curtail STH infection in the community, MDA should be regularized and environmental sanitation measures need to be improved by effective community-based campaigns.

Biodecolorization and Bioremediation of Denim Industrial Wastewater by Adapted Bacterial Consortium Immobilized on Inert Polyurethane Foam (PUF) Matrix: A First Approach with Biobarrier Model.

The present experiments were studied on bioremediation of denim industry wastewater by using polyurethane foam (PU foam) immobilized bacterial cells. About 30 indigenous adapted bacterial strains were isolated from denim textile effluent out of which only four isolates were found to be efficient against crude indigo carmine degradation using broth decolorization method. The selected bacterial strains were identified as Actinomyces sp., (PK07), Pseudomonas sp., (PK18), Stenotrophomonas sp., (PK23) and Staphylococcus sp., (PK28) based on microscopic and biochemical characteristics. The bacterial immobilized cells have the highest number of viable cells (PK07, PK18, PK23 and PK28 appeared to be 1 x 10(8), 1 x 10(9), 1 x 10(6) and 1 x 10(7) CFU/ml respectively) and maximum attachment efficiency of 92% on PU foam. The complete degradation using a consortium of PU foam immobilized cells was achieved at pH 6, 27 degrees C, 100% of substrate concentration and allowed to develop biofilm for one day (1.5% W/V). In SEM analysis, it was found that immobilization of bacterial cells using PUF stably maintained the production of various extracellular enzymes at levels higher than achieved with suspended forms. Finally, isatin and anthranilic acid were found to be degradation products by NMR and TLC. The decolorized dye was not toxic to monkey kidney cell (HBL 100) at a concentration of 50 µl and 95% of cell viability was retained. A mathematical model that describes bacterial transport with biodegradation involves a set of coupled reaction equations with non-standard numerical approach based on the time step scheme.

Bioassay guided fractionation and identification of active anti-inflammatory constituent from Delonix elata flowers using RAW 264.7 cells.

CONTEXT: Delonix elata (L.) Gamble (Fabaceae) has been used in the Indian traditional medicine system to treat rheumatism and inflammation. AIM: To assess the anti-inflammatory effect of Delonix elata flowers and to isolate the active principle. MATERIALS AND METHODS: The prompt anti-inflammatory constituent was isolated from Delonix elata flower extracts using bioassay guided fractionation in liposaccharide (LPS) stimulated RAW 264.7 macrophage cell line. The anti-inflammatory activity of extracts/fractions/sub-fractions/compounds (10, 25, and 50 µg/ml) was evaluated by estimating the levels of nitric oxide (NO), TNF-α, and IL-1ß after 24 h of LPS induction (1 µg/ml). The isolated active compound was subjected to NMR, IR, and UV analyses for structure determination. RESULTS: In an attempt to search for anti-inflammatory constituents, the active pure principle was isolated and crystallized as a white compound from Delonix elata flowers methanol extract. This active compound (50 µg/ml) decreased the release of inflammatory mediators levels such as NO (0.263 ± 0.03 µM), TNFα (160.20 ± 17.57 pg/ml), and IL-1ß (285.79 ± 15.16 pg/ml) significantly (p < 0.05); when compared to the levels of NO (0.774 ± 0.08 µM), TNFα (501.71 ± 25.14 pg/ml), and IL-1ß (712.68 ± 52.25 pg/ml) from LPS-stimulated macrophage cells. The active compound was confirmed as hesperidin with NMR, IR, and UV spectroscopy data. This is the first report of this compound from Delonix elata flowers. CONCLUSION: The findings of the study support the traditional use of Delonix elata flowers to treat inflammation.

Serious harm from inpatient hypoglycaemia: a survey of hospitals in the UK.

AIM: To estimate the incidence of serious harm to inpatients with diabetes from hypoglycaemia. METHOD: An anonymised questionnaire was e-mailed to lead organisers at the 142 acute NHS Trusts that contributed to the National Diabetes Inpatient Audit 2012. Each diabetes team was asked collectively to recall and report any serious adverse events from inpatient hypoglycaemia in the previous year. A total of 83 Trusts agreed to participate. Serious harm was defined as death, a cardiac or cerebral event or a fall resulting in permanent physical injury or fracture. RESULTS: A total of 41 Trusts returned the survey. Of these, only 28 (68.3%) were confident that robust methods existed in their Trust to ensure all such events were reported, and only 23 (56.1%) were confident that all such events were reported to the diabetes team. Despite these reporting concerns, the retrospective nature of the survey and the reliance on recall, 12 serious adverse events were reported from nine trusts: three deaths; two cases of permanent cerebral damage; two successfully resuscitated cardiac arrests; three seizures; and two undefined events. Insulin therapy was implicated in 10 events. Importantly, three events with two deaths occurred in patients who had received insulin/dextrose to correct hyperkalaemia; only one of whom had diabetes. CONCLUSIONS: An alarming number of serious adverse events was reported: 12 serious adverse events with three deaths over a 1-year period in 41 Trusts. This may be the tip of the iceberg, considering the potential under-reporting. Robust reporting mechanisms are required to determine the full extent of this serious preventable harm.

Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation.

BACKGROUND: Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. CASE REPORT: We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. CONCLUSION: Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status.

Editorial. Oral submucous fibrosis: revised hypotheses as to its cause.

Oral submucous fbrosis (OSF), being a prototype of pathological fbrosis, remains enigmatic as regards its causation. The connective tissue production is permanent and there is no reversal of the condition even after cessation of the habit of areca-nut usage; prime suspect in its causation.(1) The bulk of the connective tissue consists of type-1 collagen(2) and its formation does not appears to be caused by excessive proliferation of fbroblasts.(3) The effect of areca nut extract on in vitro fbroblasts varies on a concentration gradient, predominantly suppressing rather than stimulating the growth of the cells.(4) Based on morphological characteristics, the fbroblast population in the diseased mucosa has been classifed in to types F1, F2 and F3 with F3 cells producing signifcantly more collagen than the other two cell types. It was concluded that a change of fbroblast population has occurred in OSF and that this relative increase of F3 cells in humans, could be committed to the production of large quantities of collagen formation in OSF. It has been proposed that fbroblasts are functionally heterogeneous, the composition of any given normal or diseased connective tissue being a consequence in part of its particular mixture of fbroblast subtypes and density. Subtype deletion or amplifcation can result from selective cytotoxic or mitogenic responses induced by the binding environmental ligands.(5) Against this backdrop, we propose few de-novo attributes, hitherto unreported, and seem to be of relevance in the pathogenesis of OSF; namely the role of autophagy in basic cellular homeostatic process, important to cell fate decisions under conditions of stress and also ECM producing cells (fbroblasts, myofbroblasts and smooth muscle cells) derived from epithelial and endothelial cells through process termed epithelial and endothelial-mesenchymal transition.

Effect of incident angle on weld microstructure and mechanical properties of laser beam welded nitronic -50 austenitic stainless steel joints.

3 mm thick nitronic-50 stainless steel sheets were successfully butt-joined using a 2 kW fiber laser beam welding. Three weld joints were fabricated for different incident angles, namely, 70°, 80° and 90° for the other constant welding process parameters. The effect of incident angle on the weld bead geometry, microstructure evolution, and strength of the laser beam welded joints was studied in detail. The incident angle significantly affected the bead geometry and its orientation. Lowering the incident angle beyond a limit caused the beam shift near the weld root of the joint, where the bead was formed away from the joint line resulting in improper fusion and a defective weld occurred. The microstructure transformed from columnar to an equiaxed dendritic structure at the center of the weld nugget for lower incident angles. Skeletal and lathy ferrite was observed in the joints' weld zone. However, the fraction of lathy ferrite was higher at lower incident angles due to a faster cooling rate. A higher weld joint strength of 1010 MPa (97% of the base metal UTS) was achieved at an 80° incident angle, owing to the formation of more equiaxed dendritic grains and the absence of the secondary phases. All of the tensile test samples showed evidence of ductile failure, and overall, an acceptable level of elongation was achieved.

Anthropogenic nexus on organochlorine pesticide pollution: a case study with Tamiraparani river basin, South India.

The levels of 17 organochlorine pesticides residues (OCPs) in surface water and sediments from Tamiraparani river basin, South India were investigated to evaluate their potential pollution and risk impacts. A total of 96 surface water and sediment samples at 12 sampling stations were collected along the river in four seasons during 2008-2009. The ΣOCP concentrations in surface water and sediments were in the range of 0.1 to 79.9 ng l(-1) and 0.12 to 3,938.7 ng g(-1) dry weight (dw), respectively. Among the OCPs, the levels of dichlorodiphenyltrichloroethanes (DDTs), aldrin, dieldrin, cis-chlordane, trans-chlordane, and mirex were dominant in the sediments. The dominant OCPs in water samples are heptachlor, o,p'-DDE, dieldrin, o,p'-DDD, and mirex, which show different source of contamination pattern among sampling seasons. The distribution pattern of DDTs, hexachlorocyclohexane, and other OCPs in the present study shows heterogenic nature of nonpoint source of pollution. Notable contamination of water and sediment sample that was observed in upstream (S2) 58 ng l(-1) and downstream (S11) 1,693 ng g(-1) dw explains agricultural and municipal outfalls, whereas frequent damming effect reduces the concentration level in the midstream. The overall spatial-temporal distribution pattern of ΣOCP residues are illustrated by GIS package.

Evidence for transforming growth factor-beta 3 gene polymorphism in non-syndromic cleft lip and palate patients from Indian sub-continent.

OBJECTIVES: Orofacial clefts are major human birth defects with complex etiology. Previous studies have proposed Transforming growth factor - beta 3 (TGF-ß3) gene as a key player in contributing to non-syndromic cleft lip and palate, however none of the studies have yet included Indian population. Hence this study was designed to detect TGF-ß3 gene polymorphism in nonsyndromic cleft lip and palate patients from Indian population which is genetically distinct from previously studied populations. STUDY DESIGN: Peripheral blood samples of forty non-syndromic cleft lip and palate patients and forty unaffected individuals were collected for a case - control study design. Ethical clearance from the institutional review board and informed consent from all subjects was obtained. DNA extracted from the cases and controls was amplified using polymerase chain reaction (PCR) with TGF-ß3 specific primers. The obtained fragments were sequenced and TGF-ß3 gene polymorphisms were assessed based on the number of CA repeats. RESULTS: Chi -square test was used to compare the case and control groups. Results showed a significant difference in the number of CA repeats between the case and the control groups (p=0.01). CONCLUSION: This study confirms the crucial role of TGF-ß3 in the fusion of palatal shelves during development and further, provides novel evidence of TGF-ß3 gene polymorphism in the etiology of nonsyndromic cleft lip and palate in Indian subpopulation.

Neuroprotective effects of Tongtian oral liquid, a Traditional Chinese Medicine in the Parkinson's disease-induced zebrafish model.

Traditional Chinese medicine (TCM) is used in the treatment of Parkinson's disease (PD) worldwide. Tongtian Oral Liquid (TTKFY) is one such patented TCM, and a poly-herbal formulation, composed of 11 herbal constituents, which possess neuroprotective, antioxidant, pain-relieving properties. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP), a neurotoxicant is used to induce PD in animal models. The present study was aimed to evaluate the neuroprotective effects of TTKFY, on dopaminergic neuron development, antioxidant activities, and gene expression involved in the dopaminergic pathway in the MPTP-treated zebrafish model. Zebrafish larvae were treated with MPTP (70 µM) to induce PD and then by different concentrations (0.5, 1, 2, 4 ml/L) of TTKFY. Transgenic zebrafish Vmat: GFP at 5 dpf were used to observe the development of dopaminergic neurons. The activities of T-Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA) and mRNA gene expression of dopamine pathway were quantified. MPTP-treated zebrafish larvae showed degeneration of dopaminergic neurons, locomotion dysfunction, diminished activities of antioxidant enzymes, MDA accumulation, and altered gene expression of dopamine pathway. In contrast, TTKFY protected dopaminergic neurons, ameliorated behavioral impairments, antioxidant activities and mRNA gene expression of dopamine pathway in a dose-dependent manner. Thus, TTKFY confers protective effects against MPTP-induced neurotoxicity and the mechanisms of protection may be related to the recovery of dopaminergic neurons by reducing oxidative stress via restoring cellular defense mechanisms and thereby highlighting its therapeutic potential to prevent the progression of PD. Further studies are necessary to elucidate the mechanism of action of TTKFY on neuroprotection in the MPTP-induced PD model.