Fetal ultrasonography of Chiari II malformation

Chiari II malformation is a complex hindbrain malformation, embryologically presenting as a neural tube closure defect comprising of downward herniation of cerebellum, pons, medulla and fourth ventricle into the spinal canal. We present a case of Chiari II malformation depicting essential sonographic observations at 20 weeks of gestation. Such fetuses have high morbidity and mortality and early diagnosis of such a disease is essential in terms of planning including pregnancy termination or neurosurgical procedures for follow-up pregnancy. Ultrasonography is an indispensable modality for the evaluation of fetal anatomy, growth, and such congenital anomalies

Indications for implant removal: a prospective study

Background: The implants removal after fracture healing has always been an issue of controversy. After union, the implant ceases to be important and can be removed. Nevertheless, some patients require metallic implant removal due to various implant-related difficulties. Our study was aimed to identify the most common causes for removal of implant.Methods: The patients admitted for implant removal in our department were consented and included in the study. Pre-operative radiological images collected and evaluated. Post-operatively, images were taken and followed for resolution of symptoms or appearance of new problems.Results: A total of 60 patients were studied. Of these, 47 were males and 13 were females. Mean age was 33.7 years (range 4-70 years). Patient request (35% of patients) was the main indication for removal of implants. Reasons were found to be discomfort due to implant, infection, failure of implants and others.Conclusions: Belief regarding hardware removal has been set and most of them are agreed that routine removal should not be performed unless obviously indicated. In our attempt to fill this gap, we trust that routine removal should not be performed in ‘asymptomatic’ patients. The procedure should not need a big procedure than the implant fixation surgery. Procedure should be sought also as a risk like refracture, bleeding, infection, neurovascular injury and prior to surgery, proper consent to be taken and patient should be well explained. Sometimes indicated results expected after surgery can’t be fulfilled, and instead, complication can results

Strategies for coping with the costs of inpatient care: a mixed methods study of urban and rural poor in Vadodara District, Gujarat, India

Background In India, coping mechanisms for inpatient care costs have been explored in rural areas, but seldom among urbanites. This study aims to explore and compare mechanisms employed by the urban and rural poor for coping with inpatient expenditures, in order to help identify formal mechanisms and policies to provide improved social protection for health care

Role of acute viral hepatitis as a confounding factor in antituberculosis treatment induced hepatotoxicity

Background & Objective: Drug induced hepatotoxicity (DIH) is an important and commonly encountered adverse effect with antituberculosis (anti-TB) treatment. Acute viral hepatitis (AVH) is an important confounding reason which clinically, biochemically and histologically mimics DIH. Methods: The contributory role of acute viral hepatitis as a confounding factor in patients with normal baseline liver functions who developed acute hepatitis while receiving short-course anti-TB treatment was prospectively studied. The sera of all patients who developed acute hepatitis were analysed for markers for hepatitis A, B, C and E viruses. Results: Viral hepatitis was present in 15 of the 102 (14.7%) patients who developed acute hepatitis while receiving anti-TB treatment with hepatitis E virus being the most common cause Later onset of acute hepatitis [58 (5-133) vs. 26 (3-221) days; P=0.04], large elevations in aspartate aminotransferase (AST) [371 (30-2643) vs. 212 (63-1990 IU/l); P=0.03] and alanine aminotransferase (ALT) [388 (31-2997) vs. 225 (52- 1670 IU/l); P= 0.002] and a longer time for normalization of deranged liver functions [36.7 ± 13.3 vs. 24.5 ± 19.3 days; P=0.02] indicated acute viral hepatitis as the cause of liver function derangement. Interpretation & Conclusion: Our findings showed AVH in 14.7 per cent patients who developed hepatotoxicity while an anti-TB treatment. Therefore, in endemic areas, viral hepatitis should be sought after and excluded in all patients suspected to have DIH before attributing the hepatotoxic effect to the anti-TB drugs

An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference

Measures of Association for Identifying MicroRNA-mRNA Pairs of Biological Interest

MicroRNAs are a class of small non-protein coding RNAs that play an important role in the regulation of gene expression. Most studies on the identification of microRNA-mRNA pairs utilize the correlation coefficient as a measure of association. The use of correlation coefficient is appropriate if the expression data are available for several conditions and, for a given condition, both microRNA and mRNA expression profiles are obtained from the same set of individuals. However, there are many instances where one of the requirements is not satisfied. Therefore, there is a need for new measures of association to identify the microRNA-mRNA pairs of interest and we present two such measures. The first measure requires expression data for multiple conditions but, for a given condition, the microRNA and mRNA expression may be obtained from different individuals. The new measure, unlike the correlation coefficient, is suitable for analyzing large data sets which are obtained by combining several independent studies on microRNAs and mRNAs. Our second measure is able to handle expression data that correspond to just two conditions but, for a given condition, the microRNA and mRNA expression must be obtained from the same set of individuals. This measure, unlike the correlation coefficient, is appropriate for analyzing data sets with a small number of conditions. We apply our new measures of association to multiple myeloma data sets, which cannot be analyzed using the correlation coefficient, and identify several microRNA-mRNA pairs involved in apoptosis and cell proliferation

The Embedding Problem for Markov Models of Nucleotide Substitution

10.1371/journal.pone.0069187PLoS ONE87-POLN

Identification of microRNA-mRNA modules using microarray data

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are post-transcriptional regulators of mRNA expression and are involved in numerous cellular processes. Consequently, miRNAs are an important component of gene regulatory networks and an improved understanding of miRNAs will further our knowledge of these networks. There is a many-to-many relationship between miRNAs and mRNAs because a single miRNA targets multiple mRNAs and a single mRNA is targeted by multiple miRNAs. However, most of the current methods for the identification of regulatory miRNAs and their target mRNAs ignore this biological observation and focus on miRNA-mRNA pairs.</p> <p>Results</p> <p>We propose a two-step method for the identification of many-to-many relationships between miRNAs and mRNAs. In the first step, we obtain miRNA and mRNA clusters using a combination of miRNA-target mRNA prediction algorithms and microarray expression data. In the second step, we determine the associations between miRNA clusters and mRNA clusters based on changes in miRNA and mRNA expression profiles. We consider the miRNA-mRNA clusters with statistically significant associations to be potentially regulatory and, therefore, of biological interest.</p> <p>Conclusions</p> <p>Our method reduces the interactions between several hundred miRNAs and several thousand mRNAs to a few miRNA-mRNA groups, thereby facilitating a more meaningful biological analysis and a more targeted experimental validation.</p

Quantification of miRNA-mRNA Interactions

miRNAs are small RNA molecules (′ 22nt) that interact with their corresponding target mRNAs inhibiting the translation of the mRNA into proteins and cleaving the target mRNA. This second effect diminishes the overall expression of the target mRNA. Several miRNA-mRNA relationship databases have been deployed, most of them based on sequence complementarities. However, the number of false positives in these databases is large and they do not overlap completely. Recently, it has been proposed to combine expression measurement from both miRNA and mRNA and sequence based predictions to achieve more accurate relationships. In our work, we use LASSO regression with non-positive constraints to integrate both sources of information. LASSO enforces the sparseness of the solution and the non-positive constraints restrict the search of miRNA targets to those with down-regulation effects on the mRNA expression. We named this method TaLasso (miRNA-Target LASSO)

Identification of links between small molecules and miRNAs in human cancers based on transcriptional responses

The use of small molecules to target miRNAs is a new type of therapy for human diseases, particularly cancers. We proposed a novel high-throughput approach to identify the biological links between small molecules and miRNAs in 23 different cancers and constructed the Small Molecule-MiRNA Network (SMirN) for each cancer to systematically analyze the properties of their associations. In each SMirN, we partitioned small molecules (miRNAs) into modules, in which small molecules (miRNAs) were connected with one miRNA (small molecule). Almost all of the miRNA modules comprised miRNAs that had similar target genes and functions or were members of the same miRNA family. Most of the small molecule modules involved compounds with similar chemical structures, modes of action, or drug interactions. These modules can be used to identify drug candidates and new indications for existing drugs. Therefore, our approach is valuable to drug discovery and cancer therapy