Prevalence and severity of dental caries and treatment needs among population in the Eastern states of India

The present epidemiological investigation was conducted on a total sample of 2067 individuals in the age groups of 5-6, 15-16 and 30-35 years belonging to urban (U) and rural (R) areas of three states of eastern region of India viz. West Bengal (U & Rn = 361 & 359), Orissa (U & Rn = 351 & 351) and Sikkim (U & Rn = 323 & 321). Dental caries recording was done according to WHO index 1983. The point prevalence of dental caries, deft/DMFT and defs among all the three age groups in the urban and rural areas of three states revealed common pattern i.e. (i) Dental caries was higher in 5-6 year old children (U & R - W.B. = 52.4% & 48.3%, Orissa = 56.0% & 48.7% and Sikkim = 61.8% and 22.0% exception) as compared to 15-16 years (U & R.- WB. = 21.0% & 15.2%, Orissa = 18.3% & 19.8%, and Sikkim = 30.1% & 17.9%) and 30-35 year old individuals (U & R WB = 19.4% & 18.1% Orissa = 24.3% & 20.1% and Sikkim 29.9% & 24.5%) in West Bengal, Orissa and Sikkim respectively, (ii) dental caries was higher in urban as compared to rural areas. The decayed (d/D) component contributed maximum to total deft/DMFT and defs/DMFS score, followed by e/M (missing due to caries) and f/F component (filling) which was negligible or absent. Teeth requiring various type of treatment found that one or two surface fillings were maximum followed by others. Fluoride content of drinking water was negligible (0.004 - 0.011 ppm).     

Identification of 5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine as novel orally bioavailable and metabolically stable antimalarial compound for further exploration

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin-based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold-hopping approach combined with docking studies for putative-binding interactions with Plasmodium falciparum phosphatidylinositol-4-kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME-PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC₅₀ = 29 nM) with meager in vitro intrinsic clearance, moderate plasma-protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies.     

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young’s modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.     

Unmet Needs in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role. Invariant natural killer T cells, which are triggered specifically by lipid antigens, may protect against progression of subclinical atherosclerosis. However, currently our recommendation is that clinicians should focus on optimal management of standard CVD risk factors such as smoking, blood pressure and lipid levels. Fatigue is one of the most common and most limiting symptoms suffered by patients with SLE. The cause of fatigue is multifactorial and disease activity does not explain this symptom. Consequently, therapies directed towards reducing inflammation and disease activity do not reliably reduce fatigue and new approaches are needed. Currently, we recommend asking about sleep pattern, optimising pain relief and excluding other causes of fatigue such as anaemia and metabolic disturbances. For the subgroup of patients whose disease activity is not fully controlled by standard treatment regimes, a range of different biologic agents have been proposed and subjected to clinical trials. Many of these trials have given disappointing results, though belimumab, which targets B lymphocytes, did meet its primary endpoint. New biologics targeting B cells, T cells or cytokines (especially interferon) are still going through trials raising the hope that novel therapies for patients with refractory SLE may be available soon.     

Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis

Background  

The aim of this meta-analysis was to determine if severity assessment tools can be used to guide decisions regarding intensive care unit (ICU) admission of patients with community-acquired pneumonia.     

Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project

Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.     

Indolylquinoline derivatives are cytotoxic to Leishmania donovani promastigotes and amastigotes in vitro and are effective in treating murine visceral leishmaniasis

A wide variety of biologically active compounds contain indole and quinoline nuclei. Some novel indolylquinoline derivatives were synthesized from indole by Friedel-Crafts acylation reaction. Out of the four derivatives tested, 2-(2'-acetamidobenzyl)-3-(3'-indolylquinoline) (C) had no effect on the promastigotes or amastigotes of Leishmania donovani in vitro. The remaining three analogues, 2-(2'-dichloroacetamidobenzyl)-3-(3'-indolylquinoline) (A), 2-(2'-chloroacetamidobenzyl)-3-(3'-indolylquinoline) (B), and 2-(2'-aminobenzyl)-3-(3'-indolylquinoline) (D), inhibited the growth of L. donovani promastigotes in vitro and were cytotoxic to both the promastigote and amastigote forms of the parasite. These three derivatives were also effective in eliminating L. donovani amastigotes from BALB/c mouse peritoneal macrophages in vitro. One indolylquinoline derivative [A] was used to treat established visceral leishmaniasis in BALB/c mice. This compound was significantly more effective than sodium antimony gluconate (SAG) in reducing the splenic parasite load at a much lower concentration (5% of SAG). Our results suggest that indolylquinoline derivatives may be exploited as antileishmanial agents.