The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns

<p>Abstract</p> <p>Background</p> <p>Children born to HIV+ mothers are exposed intra-utero to several drugs and cytokines that can modify the developing immune system, and influence the newborn's immune response to infections and vaccines. We analyzed the relation between the distribution of cord blood lymphocyte subsets and cytokine profile in term newborns of HIV+ mothers using HAART during pregnancy and compared them to normal newborns.</p> <p>Methods</p> <p>In a prospective, controlled study, 36 mother-child pairs from HIV+ mothers and 15 HIV-uninfected mothers were studied. Hematological features and cytokine profiles of mothers at 35 weeks of pregnancy were examined. Maternal and cord lymphocyte subsets as well as B-cell maturation in cord blood were analyzed by flow cytometry. The non-stimulated, as well as BCG- and PHA-stimulated production of IL2, IL4, IL7, IL10, IL12, IFN-γ and TNF-alpha in mononuclear cell cultures from mothers and infants were quantified using ELISA.</p> <p>Results</p> <p>After one year follow-up none of the exposed infants became seropositive for HIV. An increase in B lymphocytes, especially the CD19/CD5+ ones, was observed in cord blood of HIV-exposed newborns. Children of HIV+ hard drug using mothers had also an increase of immature B-cells. Cord blood mononuclear cells of HIV-exposed newborns produced less IL-4 and IL-7 and more IL-10 and IFN-γ in culture than those of uninfected mothers. Cytokine values in supernatants were similar in infants and their mothers except for IFN-γ and TNF-alpha that were higher in HIV+ mothers, especially in drug abusing ones. Cord blood CD19/CD5+ lymphocytes showed a positive correlation with cord IL-7 and IL-10. A higher maternal age and smoking was associated with a decrease of cord blood CD4+ cells.</p> <p>Conclusions</p> <p>in uninfected infants born to HIV+ women, several immunological abnormalities were found, related to the residual maternal immune changes induced by the HIV infection and those associated with antiretroviral treatment. Maternal smoking was associated to changes in cord CD3/CD4 lymphocytes and maternal hard drug abuse was associated with more pronounced changes in the cord B cell line.</p

Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular Function

Recent advances have led to the emergence of molecular biomechanics as an essential element of modern biology. These efforts focus on theoretical and experimental studies of the mechanics of proteins and nucleic acids, and the understanding of the molecular mechanisms of stress transmission, mechanosensing and mechanotransduction in living cells. In particular, single-molecule biomechanics studies of proteins and DNA, and mechanochemical coupling in biomolecular motors have demonstrated the critical importance of molecular mechanics as a new frontier in bioengineering and life sciences. To stimulate a more systematic study of the basic issues in molecular biomechanics, and attract a broader range of researchers to enter this emerging field, here we discuss its significance and relevance, describe the important issues to be addressed and the most critical questions to be answered, summarize both experimental and theoretical/computational challenges, and identify some short-term and long-term goals for the field. The needs to train young researchers in molecular biomechanics with a broader knowledge base, and to bridge and integrate molecular, subcellular and cellular level studies of biomechanics are articulated.National Institutes of Health (U.S.) (grant UO1HL80711-05 to GB)National Institutes of Health (U.S.) (grant R01GM076689-01)National Institutes of Health (U.S.) (grant R01AR033236-26)National Institutes of Health (U.S.) (grant R01GM087677-01A1)National Institutes of Health (U.S.) (grant R01AI44902)National Institutes of Health (U.S.) (grant R01AI38282)National Science Foundation (U.S.) (grant CMMI-0645054)National Science Foundation (U.S.) (grant CBET-0829205)National Science Foundation (U.S.) (grant CAREER-0955291

Nonmechanical Revision Indications Portend Certain Limb-Salvage Failure Following Total Femoral Replacement

Background: There is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode. Methods: We performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure. Results: Forty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p =0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001). Conclusions: TFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation. Level of Evidence: Therapeutic Level I