EXISTING AND NOVEL THERAPIES FOR PSORIASIS

Psoriasis is adjudged as prototypic papulosquamous skin condition attributed by the erythematous papules (or) plaques. It occurs at any age but commonly seen in age groups of 20–30 and 50–60 years. Psoriasis affects around 2% of the world population. Psoriasis has a broad spectrum of skin indications occurring in different forms with common characteristics. It is clinically classified as non-pustular and pustular psoriasis. Existing therapies include topical therapy, systematic therapy, and phototherapy. Biological drugs and novel immunological factors have been identified as alternative therapy to conventional therapies. These biological drugs show more efficacies with fewer side effects in long-term application

RECENT TRENDS IN MANAGEMENT OF KERATOCONJUNCTIVITIS SICCA (DRY EYE DISEASE)

At the air-water interface, the tear film lipid layer (TFLL), a combination of lipids and proteins plays an important role in surface tension of the tear and is necessary for the physiological hydration of the ocular surface and maintenance of ocular homeostasis. Alteration in lacrimal fluid rheology, differences in lipid constitution or down regulation of particular tear proteins are found in maximum types of ocular surface disease including dry eye disease (DED). Dry eye is a disorder of the tear film due to tear deficiency or excessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of discomfort. It results in changes on the ocular surface epithelia causing reduced tear quantity and surface sensitivity which leads to inflammation reactions. Managing this inflammation is very helpful in dry eye disease patients. In this article we revise the current understanding of tear film properties, ocular surface and review the effectiveness of topically applied tear supplements, thermo sensitive atelocollagen punctal plug, subtrasal ultrasonic transducers, novel liposome based gelling tear formation and insulin based ophthalmic delivery systems which help in restoring the healthy tear film

Effect of epidural volume extension with colloid on dose requirement for intrathecal spinal block: a double blind prospective study

Background: Epidural volume extension (EVE) is a modification of combined- spinal epidural anaesthesia (CSEA) in which fluid is injected in epidural space after the intrathecal block. Fluid in epidural space compress subarachnoid space and causes cephalic spread of intrathecal drug to increase block height. Purpose of study is to determine efficacy of EVE on dose requirement of intrathecal bupivacaine when colloid was used for EVE.Methods: Sixty patients of ASA physical status I or II, scheduled for elective caesarean sections were recruited and randomized into two groups (30 each group). Group 1: CSEA in which spinal block is followed by 10 ml Colloid (HES 6%) in epidural space; Group 2: CSEA but no fluid in epidural space. Onset of sensory block and hemodynamic variables were measured at 5 min. intervals up to 40 minutes then at 10 min. intervals till end of surgery. Ineffective block was top- up by epidural 0.5% bupivacaine in incremental doses.Results: Median effective dose of intrathecal bupivacaine was significantly lower, 4.0 mg (95% CI 4.40-5.60) in group 1 versus 7.0 mg (95% CI 6.93-7.61) in group 2. Only 11 patients required ephedrine in group 1 versus 20 in group 2. Requirement of ephedrine was significantly lower 2.20 (±2.94) mg in group 1 versus 4.0 (±2.88) mg groups 2. Changes in haemodynamic variables from baseline were significantly lower in group 1 than those in group 2.Conclusions: EVE with colloid was effective in lowering dose requirement of spinal bupivacaine while patients hemodynamically were more stable.

Functional outcome of hybrid external fixator in proximal tibial fractures Schatzker type V and VI with Gustillo grade-II

Background: Management of high energy tibial plateau fractures along with extensive soft tissue damage is still challenging to many orthopaedic surgeons. This study evaluates the purpose of hybrid external fixator intreating high energy tibial plateau fractures with minimal invasion and accurate reduction.Methods: Twenty patients with high energy Schatzker type V and VI tibial plateau fractures with severe soft tissue injury were enrolled into the study in RNT medical college, Udaipur.Results: The results- bony union, range of movements and associated complications were assessed. All fractures united in an average time period of 20 weeks. Ten patients developed knee stiffness, five patients developed delayed union andthreenon-union.15 patients required split skin graft. Final outcome showed excellent score in 53 patients.Conclusions: Hybrid external fixation is a safe option for managing complex high energy tibial plateau fractures by simultaneously providing adequate fracture stabilization and necessary protection to soft tissue healing to achieve bony union

Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells

Personalized in vitro models for dysplasia and carcinogenesis in the pancreas have been constrained by insufficient differentiation of human pluripotent stem cells (hPSCs) into the exocrine pancreatic lineage. Here, we differentiate hPSCs into pancreatic duct-like organoids (PDLOs) with morphological, transcriptional, proteomic, and functional characteristics of human pancreatic ducts, further maturing upon transplantation into mice. PDLOs are generated from hPSCs inducibly expressing oncogenic GNAS, KRAS, or KRAS with genetic covariance of lost CDKN2A and from induced hPSCs derived from a McCune-Albright patient. Each oncogene causes a specific growth, structural, and molecular phenotype in vitro. While transplanted PDLOs with oncogenic KRAS alone form heterogenous dysplastic lesions or cancer, KRAS with CDKN2A loss develop dedifferentiated pancreatic ductal adenocarcinomas. In contrast, transplanted PDLOs with mutant GNAS lead to intraductal papillary mucinous neoplasia-like structures. Conclusively, PDLOs enable in vitro and in vivo studies of pancreatic plasticity, dysplasia, and cancer formation from a genetically defined background

A study of bronchial asthma in school going children in Southern part of Rajasthan

Background: Asthma is a chronic and common inflammatory disease involving mainly large airways of lungs. Childhood asthma is common chronic illness among school going children and is usually underdiagnosed and undertreated. The aim of the present study was to find out of the prevalence of Bronchial asthma in school going children of age group 6-12 years in southern part of Rajasthan (India), and its relation with gender, socio-economic status and heredity.Methods: A questionnaire-based study has been carried out in 1500 children of 6 to 12 years age group in four schools of Udaipur city (Rajasthan, India) with a response rate of 60.23% (904/1500).Results: The overall prevalence of asthma observed is 4.75% (43/904). The prevalence is higher among boys (5.55%) as compared to girls (3.75%). Further the prevalence is higher in upper (7.18%) and upper middle class (7.14%) children as compared to lower middle (4.84%) and upper lower class (2.01%) socioeconomic status. The children with positive family history of asthma also have higher prevalence (26.31%) of asthma.Conclusions: The prevalence of childhood asthma in Udaipur city is relatively lower and supports the already reported relation with gender, socioeconomic status and heredity.

Primary tubercular caecal perforation: a rare clinical entity

<p>Abstract</p> <p>Background</p> <p>Intestinal tuberculosis is a common problem in endemic areas, causing considerable morbidity and mortality. An isolated primary caecal perforation of tubercular origin is exceptionally uncommon.</p> <p>Case presentation</p> <p>We report the case of a 39 year old male who presented with features of perforation peritonitis, which on laparotomy revealed a caecal perforation with a dusky appendix. A standard right hemicolectomy with ileostomy and peritoneal toileting was done. Histopathology revealed multiple transmural caseating granulomas with Langerhans-type giant cells and acid-fast bacilli, consistent with tuberculosis, present only in the caecum.</p> <p>Conclusions</p> <p>We report this extremely rare presentation of primary caecal tuberculosis to sensitize the medical fraternity to its rare occurrence, which will be of paramount importance owing to the increasing incidence of tuberculosis all over the world, especially among the developing countries.</p

Network analysis of human protein location

<p>Abstract</p> <p>Background</p> <p>Understanding cellular systems requires the knowledge of a protein's subcellular localization (SCL). Although experimental and predicted data for protein SCL are archived in various databases, SCL prediction remains a non-trivial problem in genome annotation. Current SCL prediction tools use amino-acid sequence features and text mining approaches. A comprehensive analysis of protein SCL in human PPI and metabolic networks for various subcellular compartments is necessary for developing a robust SCL prediction methodology.</p> <p>Results</p> <p>Based on protein-protein interaction (PPI) and metabolite-linked protein interaction (MLPI) networks of proteins, we have compared, contrasted and analysed the statistical properties across different subcellular compartments. We integrated PPI and metabolic datasets with SCL information of human proteins from LOCATE and GOA (Gene Ontology Annotation) and estimated three statistical properties: Chi-square (χ²) test, Paired Localisation Correlation Profile (PLCP) and network topological measures. For the PPI network, Pearson's chi-square test shows that for the same SCL category, twice as many interacting protein pairs are observed than estimated when compared to non-interacting protein pairs (χ²= 1270.19, <it>P-value </it>< 2.2 × 10^-16), whereas for MLPI, metabolite-linked protein pairs having the same SCL are observed 20% more than expected, compared to non-metabolite linked proteins (χ²= 110.02, <it>P-value </it>< 2.2 x10^-16). To address the issue of proteins with multiple SCLs, we have specifically used the PLCP (Pair Localization Correlation Profile) measure. PLCP analysis revealed that protein interactions are majorly restricted to the same SCL, though significant cross-compartment interactions are seen for nuclear proteins. Metabolite-linked protein pairs are restricted to specific compartments such as the mitochondrion (<it>P-value </it>< 6.0e-07), the lysosome (<it>P-value </it>< 4.7e-05) and the Golgi apparatus (<it>P-value </it>< 1.0e-15). These findings indicate that the metabolic network adds value to the information in the PPI network for the localisation process of proteins in human subcellular compartments.</p> <p>Conclusions</p> <p>The MLPI network differs significantly from the PPI network in its SCL distribution. The PPI network shows passive protein interaction, possibly due to its high false positive rate, across different subcellular compartments, which seem to be absent in the MLPI network, as the MLPI network has evolved to maintain high substrate specificity for proteins.</p

Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer

CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. Results Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. Conclusions Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.Fil: Jain, Shantanu. No especifíca;Fil: Bakolitsa, Constantina. No especifíca;Fil: Brenner, Steven E.. No especifíca;Fil: Radivojac, Predrag. No especifíca;Fil: Moult, John. No especifíca;Fil: Repo, Susanna. No especifíca;Fil: Hoskins, Roger A.. No especifíca;Fil: Andreoletti, Gaia. No especifíca;Fil: Barsky, Daniel. No especifíca;Fil: Chellapan, Ajithavalli. No especifíca;Fil: Chu, Hoyin. No especifíca;Fil: Dabbiru, Navya. No especifíca;Fil: Kollipara, Naveen K.. No especifíca;Fil: Ly, Melissa. No especifíca;Fil: Neumann, Andrew J.. No especifíca;Fil: Pal, Lipika R.. No especifíca;Fil: Odell, Eric. No especifíca;Fil: Pandey, Gaurav. No especifíca;Fil: Peters Petrulewicz, Robin C.. No especifíca;Fil: Srinivasan, Rajgopal. No especifíca;Fil: Yee, Stephen F.. No especifíca;Fil: Yeleswarapu, Sri Jyothsna. No especifíca;Fil: Zuhl, Maya. No especifíca;Fil: Adebali, Ogun. No especifíca;Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Patra, Ayoti. No especifíca;Fil: O'Donnell Luria, Anne. No especifíca;Fil: Ng, Pauline C.. No especifíca;Fil: Shon, John. No especifíca;Fil: Veltman, Joris. No especifíca;Fil: Zook, Justin M.. No especifíca