Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function.

Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.

Non - DOTS regimens under RNTCP: reasons for initiation and treatment outcome.

Nearly 1% of the patients registered under RNTCP are put on non-DOTS regimens. Understanding the reasons for initiation of non- DOTS and its treatment outcome is one of the priority areas on the research agenda of RNTCP. In phase I the data of patients put on non DOTS at two TUs under Yavatmal DTC from April 2005 to March 2007 was collected from TB registers and treatment cards. In Phase II the reasons for initiating non DOTS was assessed in a sub sample by conducting two Focus group discussions with the staff at one of the TUs. In Phase III a comparison of the treatment outcome was done between patients on DOTS and Non DOTS by matched pair analysis using McNemar's chi square test. A total of 40 (1.28%) patients were put on non-DOTS. Nearly 27% of the patients on non DOTS belonged to the paediatric age group. Only one new smear positive patient and 11% of patients on retreatment after default were initiated on non-DOTS. The reasons for initiation of non DOTS was discussed for 27 patients registered at one TU in the FGDs. The main reasons for initiation of non-DOTS in new patients were drug intolerance, drug toxicity, liver disease, immunocompromised patient on ART and migration. The reasons in retreatment cases were persistent default and chronic smear positivity. The risk of un favourable outcome was significantly more in patients on non- DOTS. Many of the reasons for initiation of non-DOTS in new cases i.e. drug toxicity, intolerance; liver disease will continue to be indications for non DOTS in RNTCP areas. In some special circumstances interventions like DOTS plus and availability of ART compatible with Rifampicin will be better options for management of Tuberculosis. Default is a problem at all levels of treatment and concerted and coordinated efforts from various levels are needed to prevent it. Community DOTS providers can be involved in the programme in case of migration, some cases of persistent default and paediatric cases. The availability of Paediatric patient wise boxes will make it easier for dispensing DOTs in Paediatric Tuberculosis.

Are cardiac surgical patients at increased risk of difficult intubation?

BACKGROUND AND AIMS: Safe airway management is the cornerstone of contemporary anaesthesia practice, and difficult intubation (DI) remains a major cause of anaesthetic morbidity and mortality. The surgical category, particularly cardiac surgery as a risk factor for DI has not been studied extensively. The aim of this study was to test the hypothesis whether cardiac surgical patients are at increased risk of DI. METHODS: During the study, 627 patients (329 cardiac and 298 non-cardiac surgical) were enrolled. Pre-operative demographic and other variables associated with DI were assessed. Patients with Cormack Lehane grade III and IV or use of bougie in Cormack grade II were defined as DI. The incidence of anticipated and unanticipated DI was assessed. Factors associated with DI were described using univariate and multivariate logistic regression models. RESULTS: The overall incidence of DI was 122/627 (19.46%). The incidence of DI was higher in cardiac surgery patients (24%) as compared to non-cardiac surgery patients (14.4% P = 0.002). On multivariate analysis, factors independently associated with DI were greater age, male sex, higher Mallampati grade, and anticipated DI, but not cardiac surgery. The incidence of unanticipated DI was 48.1% and 53.4% in cardiac and non-cardiac surgery patients, respectively. CONCLUSION: Although there was a higher incidence of DI in cardiac surgical patients, cardiac surgery is not an independent risk factor for DI. Rather, other factors play more important role. About half of the DI both in cardiac and non-cardiac surgeries were unanticipated.

Development and pilot testing of HIV screening program integration within public/primary health centers providing antenatal care services in Maharashtra, India.

BACKGROUND: The objectives of this paper are: (1) to study the feasibility and relative benefits of integrating the prevention of parent-to-child transmission (PPTCT) component of the National AIDS Control Program with the maternal and child health component of the National Rural Health Mission (NRHM) by offering HIV screening at the primary healthcare level; and (2) to estimate the incremental cost-effectiveness ratio to understand whether the costs are commensurate with the benefits. METHODS: The intervention included advocacy with political, administrative/health heads, and capacity building of health staff in Satara district, Maharashtra, India. The intervention also conducted biannual outreach activities at primary health centers (PHCs)/sub-centers (SCs); initiated facility-based integrated counseling and testing centers (FICTCs) at all round-the-clock PHCs; made the existing FICTCs functional and trained PHC nurses in HIV screening. All "functional" FICTCs were equipped to screen for HIV and trained staff provided counseling and conducted HIV testing as per the national protocol. Data were collected pre- and post- integration on the number of pregnant women screened for HIV, the number of functional FICTCs and intervention costs. Trend analyses on various outcome measures were conducted. Further, the incremental cost-effectiveness ratio per pregnant woman screened was calculated. RESULTS: An additional 27% of HIV-infected women were detected during the intervention period as the annual HIV screening increased from pre- to post-intervention (55% to 79%, p < 0.001) among antenatal care (ANC) attendees under the NRHM. A greater increase in HIV screening was observed in PHCs/SCs. The proportions of functional FICTCs increased from 47% to 97% (p < 0.001). Additionally, 93% of HIV-infected pregnant women were linked to anti-retroviral therapy centers; 92% of mother-baby pairs received Nevirapine; and 89% of exposed babies were enrolled for early infant diagnosis. The incremental cost-effectiveness ratio was estimated at INR 44 (less than 1 US$) per pregnant woman tested. CONCLUSIONS: Integrating HIV screening with the broader Rural Health Mission is a promising opportunity to scale up the PPTCT program. However, advocacy, sensitization, capacity building and the judicious utilization of available resources are key to widening the reach of the PPTCT program in India and elsewhere.

Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.

Human chromosome 11 harbors two Usher type I loci, USHIB and USHIC, which encode myosin VIIA and harmonin, respectively. The USHIC locus overlaps the reported critical interval for nonsyndromic deafness locus DFNB18. We found an IVS12+5G-->C mutation in the USHIC gene, which is associated with nonsyndromic recessive deafness ( DFNB18) segregating in the original family, S-11/12. No other disease-associated mutation was found in the other 27 exons or in the intron-exon boundaries, and the IVS12+5G-->C mutation was not present in 200 representative unaffected individuals ascertained from the same area of India. An exon-trapping assay with a construct harboring IVS12+5G-->C generated wildtype spliced mRNA having exons 11 and 12 and mRNA that skipped exon 12. We conclude that mutations of USHIC can cause both Usher syndrome type IC and nonsyndromic recessive deafness DFNB18.

Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus.

We have identified five different homozygous recessive mutations in a novel gene, TMIE (transmembrane inner ear expressed gene), in affected members of consanguineous families segregating severe-to-profound prelingual deafness, consistent with linkage to DFNB6. The mutations include an insertion, a deletion, and three missense mutations, and they indicate that loss of function of TMIE causes hearing loss in humans. TMIE encodes a protein with 156 amino acids and exhibits no significant nucleotide or deduced amino acid sequence similarity to any other gene.