Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis.

Orotate phosphoribosyltransferase (OPRT) catalyses the reversible phosphoribosyl transfer from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to orotic acid (OA) to yield orotidine 5'-monophosphate (OMP) during the de novo synthesis of nucleotides. Numerous studies have reported the inhibition of this reaction as a strategy to check diseases like tuberculosis, malaria and cancer. Insight into the inhibition of this reaction is, therefore, of urgent interest. In this study, we implemented a QM/MM framework on OPRT derived from Saccharomyces cerevisiae to obtain insights into the competitive binding of OA and OA-mimetic inhibitors by quantifying their interactions with OPRT. 4-Hydroxy-6-methylpyridin-2(1H) one showed the best inhibiting activity among the structurally similar OA-mimetic inhibitors, as quantified from the binding energetics. Our analysis of protein-ligand interactions unveiled the association of this inhibitory ligand with a strong network of hydrogen bonds, a large contribution of hydrophobic contacts, and bridging water molecules in the binding site. The ortho-substituted CH3 group in the compound resulted in a large population of π-electrons in the aromatic ring of this inhibitor, supporting the ligand binding further.

Clinical diagnostic criteria versus advanced imaging in prediction of cervical lymph node metastasis in oral squamous cell carcinomas: A magnetic resonance imaging based study.

CONTEXT AND AIM: The inaccuracies in clinical examination have been well documented, while advanced imaging modalities, including computed tomography and magnetic resonance imaging (MRI), have been shown to have superior diagnostic accuracy in detecting occult and nodal metastasis. The aim of the present study was to identify as well as evaluate the inaccuracies in clinical examination and of clinical diagnostic criteria in known cases of oral squamous cell carcinomas (OSCCs) with the help of MRI. MATERIALS AND METHODS: A total of 24 patients attending as outpatients were included in the study, while clinically diagnosed and histopathologically proven cases of OSCC were examined clinically and then subjected to advanced imaging with the help of MRI. STATISTICAL ANALYSIS USED: Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA), while paired t-test was performed for evaluating the size of tumor and lymph node recorded on clinical and imaging findings. A P < 0.05 was considered statistically significant. RESULTS: Detection of tumor size and lymph node metastasis was found to be higher in case of MRI than when accomplished by clinical staging alone, while paired t-test values for difference in results were found to be statistically significant (P < 0.05). CONCLUSIONS: The present study showed that clinical diagnostic criteria alone were not sufficient and reliable for detecting metastatic lymphadenopathy, highlighting the significance of advanced imaging modalities such as MRI for an efficient preoperative diagnostic workup, as well a tool for planning treatment in patients with OSCCs.

Appraisal of vulnerable zones of non-cancer-causing health risks associated with exposure of nitrate and fluoride in groundwater from a rural part of India.

The present investigation carried out from a rural part of Nalgonda district, Telangana, India was to know the general groundwater quality and also to measure the vulnerable zones of non-cancer-causing health risks with respect to infants, children, and adults due to the consumption of nitrate and fluoride contaminated groundwater. Groundwater samples were collected from the study area and analyzed for the major physicochemical parameters. Nitrate and fluoride contents ranged from 2 to 700 mg/L and 0.3 to 4.7 mg/L, in which 59.09% and 31.82% of the groundwater samples exceed the safe drinking water limits of 45 mg/L and 1.5 mg/L, which spread over an area of 77.59% and 25.41%, respectively. Domestic wastes, septic tank spillages, animal wastes, and nitrate composts are the prime sources of nitrate, while the fluoride-bearing minerals and phosphate fertilizers are the main sources of fluoride in the aquifer regime. Individual non-cancer-causing health index obviously suggested the nitrate as the higher health risk than fluoride. The total non-cancer-causing health index was observed to be more than the acceptable limit of 1.0 in 95.5% of the total groundwater samples concerning infants, children, and adults. The vulnerable intensity of this index appeared to be higher in infants than in children and adults due to the differences in their body weights. The spatial coverage area of very health risk is more in infants (37.45%) than that of children (36.78%) and adults (30.34%). Thus, the present study suggested suitable measures for the improvement of groundwater quality and consequently the health conditions of the locals.

Metabolism and disposition in rats, dogs, and humans of erdafitinib, an orally administered potent pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor.

This article describes in vivo biotransformation and disposition of erdafitinib following single oral dose of 3H-erdafitinib and 14C-erdafitinib to intact and bile duct-cannulated (BC) rats (4 mg/kg), 3H-erdafitinib to intact dogs (0.25 mg/kg), and 14C-erdafitinib to humans (12 mg; NCT02692677). Peak plasma concentrations of total radioactivity were achieved rapidly (Tmax: animals, 1 h; humans, 2-3 h). Recovery of drug-derived radioactivity was significantly slower in humans (87%, 384 h) versus animals (rats: 91-98%, 48 h; dogs: 81%, 72 h). Faeces was the primary route of elimination in intact rats (95%), dogs (76%), and humans (69%); and bile in BC rats (48%). Renal elimination of radioactivity was relatively low in animals (2-12%) versus humans (19%). Unchanged erdafitinib was major component in human excreta (faeces, 17%; urine, 11%) relative to animals. M6 (O-desmethyl) was the major faecal metabolite in humans (24%) and rats (intact, 46%; BC, 11%), and M2 (O-glucuronide of M6) was the prevalent biliary metabolite in rats (14%). In dogs, besides M6, majority of radioactive dose in faeces was composed of multiple minor metabolites. In humans, unchanged erdafitinib was the major circulating entity. O-demethylation of erdafitinib was the major metabolic pathway in humans and animals.

Seasonal and Spatial Variation of Groundwater Quality Vulnerable Zones of Yellareddygudem Watershed, Nalgonda District, Telangana State, India.

Evaluation of seasonal and spatial variations in vulnerable zones for poor groundwater quality is essential for the protection of human health and to maintain the crop yields. With this objective, groundwater samples were collected seasonally (i.e., pre- and post-monsoon) from the Yellareddygudem watershed of Telangana, India. These samples were analysed for major chemical parameters (pH, TDS, Ca2+, Mg2+, Na+, K+, [Formula: see text], Cl-, [Formula: see text], [Formula: see text], and F-). Geographical information system (GIS) tools were used to delineate the seasonal and spatial variations for vulnerable zones related to the drinking groundwater quality index (DGQI) and irrigation groundwater quality index (IGQI). Geochemical facies and relations, Piper diagrams, and principal component analysis indicated that the weathering, dissolution, leaching, ion exchange, and evaporation were the primary processes controlling the groundwater quality seasonally. Human influences were the secondary factors. The TDS, Na+, K+, Cl-, [Formula: see text], and F- parameters were observed to be within the drinking water quality standard limits in most post-monsoon groundwater samples. However, the DGQI showed an increase in the number of samples with unsuitable quality for drinking in the post-monsoon period compared with the pre-monsoon period. The IGQI demonstrated that the number of samples with unsuitable quality for irrigation increased in the post-monsoon period compared to the pre-monsoon period. The differences in the vulnerable zones between the pre- and post-monsoon periods were due to variations in groundwater recharge, following the topography. Thus, the present study will help decision makers to plan groundwater treatment measures within vulnerable zones.

Spatial distribution of quality of groundwater and probabilistic non-carcinogenic risk from a rural dry climatic region of South India.

Having safe drinking water is a fundamental human right, which affects directly the human health. In view of this, an effort has been made for understanding the spatial distribution of quality of groundwater in a rural dry climatic region of Andhra Pradesh, South India, and associated health risks with respect to pollutants of NO3- and F-, which cause the potential production of non-carcinogenic risk, using entropy-weighted water quality index (EWWQI) and total chronic hazard index (TCHI), where the population rely on the groundwater resource for drinking purpose. Groundwater quality observed from the present study region has an alkaline character with brackish type. The concentrations of K+, HCO3-, TDS, Na+, NO3-, F-, Mg2+ and Cl- come under the non-permissible limits in 100%, 100%, 96.67%, 90%, 73.33%, 46.67%, 13.33% and 6.67% of the groundwater samples, which deteriorate the groundwater quality, causing the health disorders. The overall groundwater quality computed, using EWWQI, ranges from 53.64 to 216.59 (122.22), which classifies the region spatially into 55%, 10% and 35% due to influences of the geogenic and anthropogenic pollutants, which are the respective medium, poor and very poor groundwater quality types prescribed for potable water. According to the TCHI evaluated with respect to pollutants of NO3- and F-, the values of TCHI for men (1.194 to 4030), women (1.411 to 4.763) and children (1.614 to 5.449) are more than its acceptable limit of one. So, the health risk of non-carcinogenic is spatially in the decreasing order of children > women > men, depending upon their sensitiveness to pollutants and also their body weights. Further, the spatial distributions of both TCH1 and EWWQI are more or less similar, following the pollution activities, which help for establishment of the fact to recognize the intensity of various vulnerable zones. Therefore, the present study suggests the suitable environmental safety measures to control the NO3-- and F--contaminated drinking water and subsequently to increase the health conditions.

Applications of geochemical and multivariate statistical approaches for the evaluation of groundwater quality and human health risks in a semi-arid region of eastern Maharashtra, India.

A qualitative approach, including geochemical and multivariate statistical approaches, is applied to evaluate the groundwater quality and human health risk, based on analytical data of 72 samples collected from a semi-arid region of eastern Maharashtra, India. The shifting of hydrochemical type from Ca2+-Na+-[Formula: see text] to Na+-Ca2+-Cl- type was observed along different flow paths. The main controlling processes observed from the chemical characterisation of the groundwater are water-rock interactions, dedolomitisation and reverse ion exchange. Simulation analysis (mass transfer) exposes the dissolution of dolomite, gypsum, halite, k-feldspar and CO2 down the simulated pathways. Around 77% of the total variance was observed from the first three principal component analyses. The high positive loadings of EC, TDS, Na+, K+, Ca2+, Cl-, [Formula: see text] and [Formula: see text] of PC1 revealed silicate weathering and reverse ion exchange followed by human activities as the contamination sources. The sources identified for high positive loadings on [Formula: see text] and [Formula: see text] of PC2 are soil CO2 and human activities. The high loadings of pH and F- in PC3 revealed fluorite dissolution and calcite precipitation. The human health risk calculated for [Formula: see text] revealed that 58% and 44% of the total groundwater samples surpassed the tolerance limit for non-carcinogenic risk of 1.0 in children and adults. The human health risk assessment for fluoride showed high hazard index values in 40% and 23% of the total groundwater samples for children and adults, respectively. The study suggests some management measures for protection of groundwater resources.

Live Case Demonstrations are Essential for the Success of Pediatric Urology Meetings in India.

PURPOSE: The purpose of the study was to survey the opinion of delegates attending national pediatric urology meeting regarding live case demonstrations (LCDs) to see whether these can be replaced with taped case demonstrations (TCDs) in future. METHODS: A questionnaire-based survey was conducted at the end of the 3-day annual conference and live operative workshop in pediatric urology. Apart from general data such as age of the respondent and type of practice setting, four key questions on LCDs with yes/no responses included: would you have attended this meeting if there were no LCDs? Are unedited videos (TCDs) as effective as LCDs for teaching? Do you think LCDs should be continued? Would you allow your child to be operated in LCD by an expert? For question 3, the outcomes were compared between junior surgeons (<45-year-old) and senior surgeons (>45-year-old). RESULTS: On analysis, 88/140 (62%) respondents (95% confidence interval [CI]: 54%-70%) said that they would not have attended the meeting if there were no LCDs; 70/139 (50%) respondents (95% CI: 42%-58%) felt that TCDs may be an effective alternative to LCDs; 129/144 (90%) respondents (95% CI: 83%-94%) felt that LCDs should be continued. For question 4, 101/129 (79%) said they would allow their child to be operated in LCD by an expert, while 28 (21%) did not agree for their child to be operated in LCD. There was no significant difference between junior and senior surgeons regarding support for LCDs (P = 0.15). CONCLUSIONS: In the Indian scenario, LCDs were favored as an essential part of pediatric urology meeting, attract more participation, and are likely to be important for the success of the meeting.

Evaluation of Nicotine Dependence in Adult Population of Eastern Nepal.

Background Tobacco consumption is a leading cause of premature death in the world. Tobaccorelated deaths are associated with cardiovascular diseases, pulmonary diseases, oral potentially malignant disorders, cancer, others. Moreover there is also associated nicotine dependence which might result to numerous tobacco-associated diseases. Objective This study was conducted to analyze the degree of nicotine dependence considering its potential health risk, in the Eastern region of Nepal. Method A descriptive questionnaire based study was conducted among current tobacco users of six districts of Eastern Nepal. Fagerstrom Test for Nicotine Dependence (FTND) and Fagerstrom Test for Nicotine Dependency for Smokeless Tobacco (FTNDST) questionnaire were used for tobacco smokers and chewers, respectively. Result Of the total participants, 836 were males and 359 females, among whom 736 were active tobacco smokers and 432 chewers, 34.8% had tried to stop consuming tobacco and 306 (25.6%) had oral lesions in white or red forms. Very low nicotine dependence was found among 244 (31.47%) tobacco smokers and 37 (8.56%) chewers whereas 36 (4.71%) smokers and 103 (23.84%) chewers had very high nicotine dependence. The mean score for FTND was 3.73±2.37 and 5.74±2.12 for FTND-ST. A significant difference in duration and age group with FTND score was observed, however not with FTND-ST. Conclusion The information regarding degree of nicotine dependence can be used as baseline information for planning of preventive strategies and implementation of tobacco cessation and control programs.

ANCA vasculitis and IgA nephropathy linked to silica exposure.

There is a recognized association between silica exposure and Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV); however, no clear association between silica exposure and Immunoglobulin A (IgA) nephropathy. We describe the case of a 26-year-old male stonemason who presents with hilar lymphadenopathy, haematuria and acute kidney injury related to silica exposure, AAV and IgA nephropathy. He was asymptomatic on presentation; urinalysis revealed glomerular haematuria (>1000 red blood cells/L) and proteinuria (protein-to-creatinine ratio 84 mg/mmol). ANCA anti-myeloperoxidase serology was strongly positive. Mediastinal lymph node biopsy revealed multiple necrotizing granulomas with silica inclusions, and renal biopsy demonstrated crescentic glomerulonephritis and mesangial IgA staining. The patient was treated with cyclophosphamide and high-dose prednisolone with subsequent improvement in renal function. To our knowledge, this is the first report of both ANCA vasculitis and IgA nephropathy in the setting of silica exposure. This case highlights the relevance of occupational exposures in renal disease, and the immune-stimulatory effect of silica.

Quality criteria for groundwater use from a rural part of Wanaparthy District, Telangana State, India, through ionic spatial distribution (ISD), entropy water quality index (EWQI) and principal component analysis (PCA).

The present study region comprises granite and granite gneisses aquifer system constituted by Precambrian rocks. Groundwater is the primary source for drinking and other domestic purposes. Many developing regions in the world suffer from lack of safe drinking water. A rural part of Wanaparthy District in Telangana State, India, is one of them. For this reason, the groundwater samples collected from the study region were analyzed for pH, TDS, Ca2+, Mg2+, Na+, K+, HCO3-, Cl-, SO42-, NO3- and F- and evaluated groundwater quality criteria, using ionic spatial distribution (ISD), entropy water quality index (EWQI) and principal component analysis (PCA). The ISD maps show that some locations are not suitable for drinking purpose due to exceeding concentrations of TDS, Mg2+, Na+, K+, HCO3-, Cl-, NO3-and F-, compared to those with national drinking water quality standards. According to the EWQI, about 3%, 47%, 43% and 7% of the total area come under the excellent, good, medium and extremely poor water quality types for drinking purpose, respectively. Chadha's diagram classified the area as carbonate hardness (63%), non-carbonate alkali (17%), carbonates alkali (13%) and non-carbonate hardness (7%) zones. The binary diagrams (Na+ + K+ vs TC, Na+ vs Ca2+ and HCO3- vs TC) indicate that the quality of groundwater is controlled by influences of water-rock interactions, mineral weathering and dissolution, ion exchange and evaporation as well as the impact of anthropogenic sources. The PCA transferred the chemical variables into three principal components accounts for about 81% of the total variance. The high positive loadings of PC1 (Cl-, TDS, SO42-, Na+, NO3-, Mg2+ and HCO3-) stand for processes of silicate weathering and dissolution, ion exchange and evaporation, and the influence of domestic waste waters, irrigation return flows and chemical fertilizers on the groundwater system, the PC2 (F- and pH) signifies the alkaline nature of groundwater, which causes fluorosis, and the PC3 (K+) is a result of potassium fertilizers. The study helps to take remediate measures at a specific site and hence suggests the treatment of water before its drinking and also the recharge of the aquifer artificially to improve the groundwater quality.

HLA-DR15-specific inhibition attenuates autoreactivity to the Goodpasture antigen.

Goodpasture's disease manifests as rapidly progressive glomerulonephritis. Current immunosuppressive treatments do not specifically target the pathological immune response and have significant side effects. Like most autoimmune diseases, the strongest genetic association is with the HLA alleles. Inheritance of HLA-DR15 confers susceptibility, and structure-function studies have shown that HLA-DR15 plays a causative role in activating autoreactive pro-inflammatory T cells. Thus, specific inhibition of HLA-DR15 would provide a targeted therapeutic approach. We hypothesised that PV-267, an HLA-DR15-specific inhibitor, would effectively block HLA-DR15 presentation of the dominant epitope, attenuate the activation of autoreactive T cells, and limit disease. Using humanised HLA-DR15 transgenic mice, α3135-145-specific, pro-inflammatory T cell recall responses were measured using IFN-γ and IL-17A ELISPOTs and by proliferation assay. To determine if PV-267 could limit disease, experimental autoimmune anti-GBM glomerulonephritis was induced in HLA-DR15 transgenic mice (on an Fcgr2b-/- background), and functional and histological disease endpoints were measured. PV-267 effectively inhibited α3135-145-specific immune responses and disease development. Mice treated prior to immunization with α3135-145 had reduced α3135-145-specific recall responses, and limited disease by albuminuria, histological glomerular injury, IgG deposition, and inflammatory cell infiltrates. PV-267 treatment commencing after the onset of active anti-α3(IV)NC1 autoimmunity attenuated functional and histological renal injury. When treatment was administered after disease was established, PV-267 limited the severity of histological injury. In conclusion, HLA-DR15 inhibition attenuates α3(IV)NC1-specific pro-inflammatory responses and could be used as an adjunct therapy for anti-GBM disease.

The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study.

BACKGROUND: ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate-to-severe AD. Methods A total of 36 patients with moderate-to-severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28-day period (20 mg, 40 mg and 80 mg once daily). RESULTS: ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg -1·3 ± 2·1, P = 0·81; 40 mg -3·1 ± 2·7, P = 0·27; 80 mg -4·7 ± 2·1, P = 0·01; placebo -1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose-dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis-associated biomarker E selectin/SELE. CONCLUSIONS: In patients with moderate-to-severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.

Diagnostic pathways in Crohn's disease.

The management of Crohn's disease (CD) is shifting from a stepwise, incremental approach based on symptom control to more aggressive early combined immunosuppression in an attempt to induce remission more rapidly and avoid long-term bowel damage. Accurately defining disease activity is a major challenge, as there is often a disconnect between symptomatology and underlying disease status. The role of imaging in CD has evolved such that it now plays a central role establishing the initial diagnosis, characterising disease phenotype, activity assessment, disease surveillance, and assessing response to therapy. Furthermore, the "treat-to-target" approach is being investigated in CD, with resolution of transmural inflammation on cross-sectional imaging being the treatment goal. In this review, we summarise the principal imaging techniques available to the radiologist, the key findings, and provide some guidance on the preferred imaging option in the diagnostic pathway. We consider the relative merits and drawbacks of each imaging technique before offering a brief discussion of some current developments and research avenues in CD imaging. We discuss how imaging may be useful in a "treat-to-target" approach. Finally, we highlight some practical considerations around service configuration and delivery to optimise imaging in CD in an accurate, cost-effective manner.

Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime.

Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells. After systemic administration of the NO-NPs, we quantitatively assessed and visualized increased tumor blood flow as well as enhanced vascular permeability than could be achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated consequential improvement in therapeutic efficacy over the control groups with considerably improved DOX intratumoral accumulation. Overall, this proof of concept study implies a high potency of the NO-NPs as an EPR enhancer to achieve better clinical outcomes.

[Comparative study of differentiation potential of mesenchymal stem cells derived from orofacial system into vascular endothelial cells].

OBJECTIVE: To compare the proliferation and capacity of differentiation to vascular endothelial cells and angiogenesis induction among stem cells from human exfoliated deciduous teeth (SHED), dental pulp stem cells (DPSC) and human bone marrow mesenchymal stem cells (BMSC) from orofacial bone. METHODS: SHED and DPSC were isolated from pulp tissue of the patients. BMSC were isolated from orthognathic or alveolar surgical sites. The surface markers of the cells were detected by flowcytometry. Cell counting kit-8 (CCK-8) assays were conducted to detect the proliferation ability of the cells. The cells were induced into endothelial cells with conditional medium and then the induced cells were cultured in Matrigel medium. The expression of angiogenesis-related genes such as platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrand Factor (vWF) were quantified by real-time PCR. The cells were cultured in chick embryo chorioallantoic membrane (CAM) and the vessels were counted after 5 days. RESULTS: The cell surface markers CD73, CD90, CD105 and CD146 of all the stem cells were positive, CD34 and CD45 were negative. The CD146 positive rate of SHED and DPSC was higher than that of BMSC. SHED had a higher proliferation rate than DPSC and BMSC. After angiogenic induction for 14 d, 3 kinds of cells emanated pseudopodia formed grid structure long vasculature in Matrigel media. The total length of tube formation of induced BMSC (7 759.7 µm) and SHED (7 734.3 µm) was higher than DPSC (5 541.0 µm). The meshes number of induced SHED (70.7) was higher than DPSC (60) and BMSC (53.7) in Matrigel medium. The expression of CD31, VEGFR2 and vWF genes of SHED were higher than those of BMSC and DPSC. VEGFR1 gene expression of BMSC was higher than that of the other groups, and SHED was higher than DPSC. The expression of VEGF showed no difference among the cells. No deference was showed between the effect of the stem cells and negative control on new formed vessels in CAM. The total length of vessels of SHED (30.4 mm) was higher than that of the negative control (20.9 mm) and BMSC (28.0 mm). CONCLUSION: SHED, DPSC and BMSC can differentiate into vascular endothelial cells. SHED showed a stronger angiogenesis differentiation and proliferation potential compared with DPSC and BMSC.

Association of vascular calcification of breast with carotid intima media thickness.

PURPOSE: To assess the relationship between breast arterial calcification (BAC) on mammography and carotid intima medial thickness (C-IMT) by comparing these patients with healthy control subjects. MATERIAL AND METHODS: The study included 100 women divided into two groups based on presence of BAC on mammography using the WIPRO GE - DMR PLUS mammography unit. The groups included 50 BAC(+) (case group) and 50 BAC(-) (control group). BAC is defined as two linear calcific deposits forming the rail-road track pattern, with ring-like appearance in cross section. Relevant previous clinical and surgical history was taken and C-IMT was measured using B-mode ultrasonography Aplio XG (Toshiba medical systems corp., Japan) using an 8-13 MHz linear transducer within 1 cm from the proximal and distal portion of the common carotid artery and the mean value was taken. RESULTS: All the participants included in this study were within the age group of 40-70 years. Mean age with BAC(+) was 59.18 ± 8.59 years and BAC(-) was 50.70 ± 7.93 years. Mean C-IMT in the BAC(+) group was 0.86 ± 0.21 mm vs. 0.71 ± 0.12 mm in the BAC(-) group. Chi-square test, independent t test and Spearman's rho correlation to assess the association of the breast arterial calcification were performed. The study showed significant difference in mean C-IMT between two groups (p value < 0.001) when correlated with age, diabetes, hypertension, presence of BAC and history of surgery and drug intake. CONCLUSIONS: BAC in mammography is independently associated with C-IMT. Furthermore, apart from age and menopausal status a statistically significant positive correlation with C-IMT was observed.

Effect of erbium ion concentration on structural and luminescence properties of lead borosilicate glasses for fiber amplifiers.

This investigation reports, the effect of the concentration of erbium and lead ions on the physical, structural and optical properties of lead borosilicate glasses. These glasses were synthesized by the melt quench method. In the synthesis, the concentration of the erbium (Er3+ ) ion was varied in the order of 0.0, 0.1, 0.5, 1.0 and 2.0 mol% and lead (Pb2+ ) ion was varied in the order of 30, 29.9, 29.5, 29 and 28 mol%. The glasses were analyzed using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and UV-vis-NIR spectroscopy. From XRD, the amorphous nature of lead borosilicate glasses was confirmed. The functional groups which were present in the glasses have been identified by analyzing the FT-IR spectrum. From the absorption spectra, the oscillator strengths as well as the Judd-Ofelt (JO) intensity parameters were determined and compared with other hosts. The JO intensity parameters were further used to calculate certain radiative properties for the excited luminescent levels of Er3+ ion. From emission spectra, full width at half maxima (FWHM), stimulated emission cross-sections (σe ) and certain lasing parameters were evaluated and compared with reference host glasses. The lifetimes of 4 I13/2 excited level of Er3+ ion have also been recorded and analyzed. The calculated and experimental lifetimes were compared in terms of quantum efficiencies. From the photoluminescence analysis, the erbium doped lead borosilicate glasses well suited for optical fiber amplifiers are discussed.

India's integrated child development services scheme: challenges for scaling up.

BACKGROUND: India had around 158 million children under the age of 6 and about 26 million births in 2015. In the same year, India's Integrated Child Development Services Scheme served about 82 million children under 6 years and over 19 million pregnant women and lactating mothers. These 102 million beneficiaries received services in about 1.3 million centres. METHOD: This paper reviews the growth of the Scheme and considers challenges to scaling up quality with equity based on results of large-scale national or multistate studies. RESULTS: The Scheme is associated with decreased malnutrition and better child development. The size and diversity of the country, the policy context, funding mode and lack of community awareness and engagement have hindered scaling up access while the approach to service delivery, low institutional capacity and poor infrastructure have impeded scaling up of implementation quality. CONCLUSIONS: This review illustrates the challenges associated with scaling-up access and implementation quality of a multicomponent, integrated early childhood programme in a large, diverse country. The future success of the Integrated Child Development Services will depend on how well it adheres to quality standards and how well it evolves to address current weaknesses.

[Comparison of the properties of CD146 positive and CD146 negative subpopulations of stem cells from human exfoliated deciduous teeth].

OBJECTIVE: Stem cells from human exfoliated teeth (SHED) were sorted by magnetically activated cell sorting (MACS) technique to obtain the CD146 positive and negative cell subpopulation. Then the biological characteristics of these subpopulations were compared to explore their specific application potential in tissue engineering. METHODS: In this study, freshly extracted deciduous teeth without any caries or dental pulp disease were obtained. SHED was isolated using enzyme digestion method and then sorted by MACS, CD146 positive cells and CD146 negative cells were obtained after cell sorting. The biological characteristics of the unsorted mixed cells, CD146 positive subpopulation and CD146 negative subpopulation were compared. The proliferation ability was detected through cell counting kit-8 (CCK-8) and colony-forming unit (CFU). After osteogenic induction, alizarin red staining was performed and the gene expression of osteogenic related markers was detected by quantitative real-time polymerase chain reaction(qPCR). After adipogenic induction, oil-red O staining was performed and the gene expression of adipogenic related markers was detected. After neurogenic differentiation induction, the expression of neural markers was detected by immunofluorescence and the gene expression of neural markers was detected by qPCR. RESULTS: SHED of the fifth passage was sorted by MACS. And the CD146 positive cell subpopulation and CD146 negative cell subpopulation were obtained. CCK8 assay showed that the proliferative tendency of the three cell groups was consistent, but the proliferation potential of CD146 positive and negative cell subpopulations was significantly lower than that of the unsorted cells. The colony forming rates of the unsorted mixed cell group, CD146 positive and negative populations were 28.6%±3%,17.1%±2.3% and 27.5%±2.5%, respectively. After 21 days of osteogenic induction, alizarin red staining and qPCR showed that the CD146 positive cell population had more mineralized nodule formation and expressed higher level of osteogenic related genes compared with the other two groups. After 21 days of adipogenic induction, oil red O staining and qPCR results showed that the CD146 negative subpopulation produced more lipid droplets and the expression of lipid related genes increased more significantly. After 14 days of neural induction, cell immunofluorescence and qPCR results showed that the unsorted mixed cell group and CD146 positive subpopulation expressed glial cell marker, and the expressions of neural precursor cells and neuronal marker increased significantly in negative subpopulation. CONCLUSION: The unsorted mixed cells showed better proliferative potential than CD146 positive and negative subpopulations. The CD146 positive subpopulation was most potent in osteogenic differentiation; it was more suitable for bone tissue engineering. The CD146 negative cells had stronger adipogenic differentiation potential than the other two cell groups; different subpopulations differed in neural differentiation.