Molecular Epidemiology of HIV-Associated Tuberculosis in Dar es Salaam, Tanzania: Strain Predominance, Clustering, and Polyclonal Disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian "GD" family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common

Variability of the pullout strength of cancellous bone screws with cement augmentation

Background Orthopaedic surgeons often face clinical situations where improved screw holding power in cancellous bone is needed. Injectable calcium phosphate cements are one option to enhance fixation. Methods Paired screw pullout tests were undertaken in which human cadaver bone was augmented with calcium phosphate cement. A finite element model was used to investigate sensitivity to screw positional placement. Findings Statistical analysis of the data concluded that the pullout strength was generally increased by cement augmentation in the in vitro human cadaver tests. However, when comparing the individual paired samples there were surprising results with lower strength than anticipated after augmentation, in apparent contradiction to the generally expected conclusion. Investigation using the finite element model showed that these strength reductions could be accounted for by small screw positional changes. A change of 0.5 mm might result in predicted pullout force changes of up to 28%. Interpretation Small changes in screw position might lead to significant changes in pullout strength sufficient to explain the lower than expected individual pullout values in augmented cancellous bone. Consequently whilst the addition of cement at a position of low strength would increase the pullout strength at that point, it might not reach the pullout strength of the un-augmented paired test site. However, the overall effect of cement augmentation produces a significant improvement at whatever point in the bone the screw is placed. The use of polymeric bone-substitute materials for tests may not reveal the natural variation encountered in tests using real bone structures.Dr V. Stadelmann (AOR, Davos, Switzerland) and Mr. M. Behrens (Stryker, Selzach, Switzerland). Professor Procter and Dr Arnoldi were employed by Stryker Trauma. Dr Bennani's PhD studies at Brunel University were funded by Stryker Trauma AG

Polyantigenic Interferon-γ Responses Are Associated with Protection from TB among HIV-Infected Adults with Childhood BCG Immunization

Surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified. HIV-infected adults with childhood BCG immunization entering the placebo arm of the DarDar TB vaccine trial in Dar es Salaam, Tanzania, were assessed for interferon gamma (IFN-γ) responses to three mycobacterial antigen preparations--secreted Mycobacterium tuberculosis antigens 85 (Ag85), early secretory antigenic target 6 (ESAT-6) and polyantigenic whole cell lysate (WCL). We investigated the association between the number of detectable IFN-γ responses at baseline and the subsequent risk of HIV-associated TB. During a median follow-up of 3.3 years, 92 (9.4%) of 979 placebo recipients developed TB. The incidence of TB was 14% in subjects with no detectable baseline IFN-γ responses vs. 8% in subjects with response to polyantigenic WCL (P = 0.028). Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB. Overall the percentage of subjects with 0, 1, 2 and 3 baseline IFN-γ responses to mycobacterial preparations who developed HIV-associated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001). Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB. ClinicalTrials.gov NCT0052195

Sarcopenia: etiology, clinical consequences, intervention, and assessment

The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence