Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12–21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with “cysts” up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism

Hull early walking aid for rehabilitation of transtibial amputees - randomized controlled trial (HEART)

Purpose To compare articulated and nonarticulated early walking aids (EWAs) for clinical and quality-of-life outcomes in transtibial amputees. Methods Patients undergoing lower limb amputation in a tertiary-care vascular surgical unit were screened over a 4-year period. Recruited patients were randomized to receive articulated amputee mobility aid (AMA) or nonarticulated pneumatic postamputation mobility aid (PPAMA) during early rehabilitation. Primary (10-meter walking velocity) and secondary clinical (number and duration of physiotherapy treatments during EWA/prosthesis use) and quality-of-life (SF-36) outcome measures were recorded at five standardized assessment visits. Inter-group and intra-group analyses were performed. Results Two hundred seventy-two patients were screened and 29 transtibial amputees (median age, 56 years) were recruited (14/treatment arm). No significant difference was seen in demographics and comorbidities at baseline. Inter-group analysis: Median 10-meter walking velocity was significantly (Mann-Whitney, P = .020) faster in the PPAMA group (0.245 m/s, interquartile range [IQR] 0.218-0.402 m/s) compared with the AMA group (0.165 m/s; IQR, 0.118-0.265 m/s) at visit 1. However, there was no difference between the groups at any other visit. Similarly, the number of treatments using EWA was significantly (P = .045) lower in the PPAMA group (5.0; IQR, 3.5-8.0) compared with the AMA group (6.0; IQR, 6.0-10.5). No difference was observed between the groups in duration of physiotherapy or SF-36 domain and summary scores. Intra-group analysis: Both treatment groups showed significant improvement in 10-meter walking velocity (Friedman test; AMA P = .001; PPAMA P = .007); however, other clinical outcomes did not show any statistically significant improvement. Only physical function domain of SF-36 demonstrated significant improvement (Friedman test; AMA P = .037; PPAMA P = .029). Conclusions There is no difference in clinical and QOL outcomes between articulated and nonarticulated EWAs in rehabilitation of transtibial amputees