Operational Challenges in Diagnosing Multi-Drug Resistant TB and Initiating Treatment in Andhra Pradesh, India

Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Comparison of Two Multilocus Sequence Based Genotyping Schemes for Leptospira Species

Two independent multilocus sequence based genotyping schemes (denoted here as 7L and 6L for schemes with 7 and 6 loci, respectively) are in use for Leptospira spp., which has led to uncertainty as to which should be adopted by the scientific community. The purpose of this study was to apply the two schemes to a single collection of pathogenic Leptospira, evaluate their performance, and describe the practical advantages and disadvantages of each scheme. We used a variety of phylogenetic approaches to compare the output data and found that the two schemes gave very similar results. 7L has the advantage that it is a conventional multi-locus sequencing typing (MLST) scheme based on housekeeping genes and is supported by a publically accessible database by which genotypes can be readily assigned as known or new sequence types by any investigator, but is currently only applicable to L. interrogans and L. kirschneri. Conversely, 6L can be applied to all pathogenic Leptospira spp., but is not a conventional MLST scheme by design and is not available online. 6L sequences from 271 strains have been released into the public domain, and phylogenetic analysis of new sequences using this scheme requires their download and offline analysis

The neurobiology of mouse models syntenic to human chromosome 15q

Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11–q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11–q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABAA subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11–q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11–q13 and their relationships to autism

Magnetic Properties of Iron-Rich Mixed Rare-Earth Sm₂-ₓTbₓFe\u3csub\u3e17-y\u3c/sub\u3eSi\u3csub\u3ey\u3c/sub\u3e Compounds

A series of Sm2-xTbxFe17-ySiy solid solutions with x = 0, 1, and 1.5 and y = 1, 2, and 3 were prepared by induction melting stoichiometric amounts of high purity elements. The x-ray diffraction data confirm that the postannealed samples are 2:17 intermetallics of the R3 space group. The lattice parameters and the unit cell volumes were calculated using a modified Rietveld program. The fitted intensities showed behavior related to a disordered rhombohedral structure as inferred from neutron data. It was observed that for a particular y, the unit cell volume decreased almost linearly with increasing Tb content (x = 0, 1, and 1.5). The unit cell volume decreases with increasing Si content (y) for a particular x as is also observed for the single rare-earth 2:17 compounds. The Curie temperature measurements show that with increasing Tb content x a decrease in the Curie temperatures of about 3% for y = 1, 10% for y = 2, and 15% for y = 3 was observed. For a particular x, a nearly linear type increase in the Curie temperature resulted with increasing silicon content (y ≤ 3). It was observed that with increasing x there was a decrease of about 40% in the magnetization for y = 1 and 2, whereas there was a decrease of about 35% for y = 3. For a particular x, the magnetization decreased almost linearly with increasing Si content (y = 1-3)

Magnetic Properties of Iron-Rich Nd₂₋yDyyFe₁₇₋ₓSiₓ Mixed Rare-Earth System

The study of structural and magnetic properties of iron rich Nd2-y DyyFe17-xSix rare-earth system was presented. The system was prepared by induction melting stoichiometric amounts of high-purity elements. It was observed that the unit-cell volume decreased linearly with increasing silicon content (x≤3) for a particular y. An additional density along the c-axis chains of Fe dumbells and rare-earth atoms was revealed by neutron diffraction

Prevalence of multidrug resistance among retreatment pulmonary tuberculosis cases in a tertiary care hospital, Hyderabad, India

Background: India is one of the high tuberculosis (TB) burden countries in the world. India ranks second in harboring multi drug resistant (MDR)-TB cases. About 50,000 of MDR cases are recorded in retreatment pulmonary TB cases. This study was conducted in a tertiary care facility (Government General and Chest Hospital) in Hyderabad, India. Objectives: Toassess: Proportion of the TB patients having MDR-TB at the initiation of retreatment regimen; the prevalence of isoniazid (INH) resistance in this geographical area. Materials and Methods: An analytical, observational, prospective cohort study of patients attending the out-patient department from December 2010 to March 2011. Results: Sputum samples from 100 patients were subjected to acid fast bacilli (AFB) culture and drug sensitivity testing. Of these, 28 (28%) were MDR-TB, 42 (42%) were non-MDR-TB and 39% being INH resistance. Conclusions: In conclusion, one third of the retreatment pulmonary TB cases attending a tertiary care institute for TB will be MDR-TB at the initiation of treatment and there is a need to include ethambutol in the continuation phase of new TB case treatment in view of high INH resistance