Risks of non-accidental mortality by baseline CD4+ T-cell strata in hepatitis-C-positive and -negative individuals initiating highly active antiretroviral therapy

BACKGROUND: Patients coinfected with hepatitis C virus (HCV) and HIV experience higher mortality rates than patients infected with HIV alone. We designed a study to determine whether risks for later mortality are similar for HCV-positive and HCV-negative individuals when subjects are stratified on the basis of baseline CD4+ T-cell counts. METHODS: Antiretroviral-naive individuals, who initiated highly active antiretroviral therapy (HAART) between 1996 and 2002 were included in the study. HCV-positive and HCV-negative individuals were stratified separately by baseline CD4+ T-cell counts of 50 cell/microl increments. Cox-proportional hazards regression was used to model the effect of these strata with other variables on survival. RESULTS: CD4+ T-cell strata below 200 cells/microl, but not above, imparted an increased relative hazard (RH) of mortality for both HCV-positive and HCV-negative individuals. Among HCV-positive individuals, after adjustment for baseline age, HIV RNA levels, history of injection drug use and adherence to therapy, only CD4+ T-cell strata of <50 cells/microl (RH=4.60; 95% confidence interval [CI] 2.72-7.76) and 50-199 cells/microl (RH=2.49; 95% CI 1.63-3.81) were significantly associated with increased mortality when compared with those initiating therapy at cell counts >500 cells/microl. The same baseline CD4+ T-cell strata were found for HCV-negative individuals. CONCLUSION: In a within-groups analysis, the baseline CD4+ T-cell strata that are associated with increased RHs for mortality are the same for HCV-positive and HCV-negative individuals initiating HAART. However, a between-groups analysis reveals a higher absolute mortality risk for HCV-positive individuals.

Memory of childbirth in the second year: the long-term effect of a negative birth experience and its modulation by the perceived intranatal relationship with caregivers

OBJECTIVE: To assess the memory of various subdimensions of the birth experience in the second year postpartum, and to identify women in the first weeks postpartum at risk of developing a long-term negative memory. DESIGN, METHOD, OUTCOME MEASURES: New mothers' birth experience (BE) was assessed 48-96 hours postpartum (T1) by means of the SIL-Ger and the BBCI (perception of intranatal relationships); early postnatal adjustment (week 3 pp: T1(bis)) was also assessed. Then, four subgroups of women were defined by means of a cluster-analysis, integrating the T1/T1(bis) variables. To evaluate the memory of the BE, the SIL-Ger was again applied in the second year after childbirth (T2). First, the ratings of the SIL-Ger dimensions of T1 were compared to those at T2 in the whole sample. Then, the four subgroups were compared with respect to their ratings of the birth experience at T2 (correlations, ANOVAs and t-tests). RESULTS: In general, fulfillment, emotional adaptation, physical discomfort, and anxiety improve spontaneously over the first year postpartum, whereas in negative emotional experience, control, and time-going-slowly no shift over time is observed. However, women with a negative overall birth experience and a low level of perceived intranatal relationship at T1 run a high risk of retaining a negative memory in all of the seven subdimensions of the birth experience. CONCLUSIONS: Women at risk of developing a negative long-term memory of the BE can be identified at the time of early postpartum, when the overall birth experience and the perceived intranatal relationship are taken into account.

A Nonstationary Negative Binomial Time Series with Time-Dependent Covariates: Enterococcus Counts in Boston Harbor

Boston Harbor has had a history of poor water quality, including contamination by enteric pathogens. We conduct a statistical analysis of data collected by the Massachusetts Water Resources Authority (MWRA) between 1996 and 2002 to evaluate the effects of court-mandated improvements in sewage treatment. Motivated by the ineffectiveness of standard Poisson mixture models and their zero-inflated counterparts, we propose a new negative binomial model for time series of Enterococcus counts in Boston Harbor, where nonstationarity and autocorrelation are modeled using a nonparametric smooth function of time in the predictor. Without further restrictions, this function is not identifiable in the presence of time-dependent covariates; consequently we use a basis orthogonal to the space spanned by the covariates and use penalized quasi-likelihood (PQL) for estimation. We conclude that Enterococcus counts were greatly reduced near the Nut Island Treatment Plant (NITP) outfalls following the transfer of wastewaters from NITP to the Deer Island Treatment Plant (DITP) and that the transfer of wastewaters from Boston Harbor to the offshore diffusers in Massachusetts Bay reduced the Enterococcus counts near the DITP outfalls.

L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells

T lymphocytes lacking the lymph node-homing receptors L-selectin and CCR7 do not migrate to lymph nodes in the steady state. Instead, we found here that lymph nodes draining sites of mature dendritic cells or adjuvant inoculation recruited L-selectin-negative CCR7- effector and memory CD8+ T cells. This recruitment required CXCR3 expression on T cells and occurred through high endothelial venules in concert with lumenal expression of the CXCR3 ligand CXCL9. In reactive lymph nodes, recruited T cells established stable interactions with and killed antigen-bearing dendritic cells, limiting the ability of these dendritic cells to activate naive CD4+ and CD8+ T cells. The inducible recruitment of blood-borne effector and memory T cells to lymph nodes may represent a mechanism for terminating primary and limiting secondary immune responses.

Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii

Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

Toxicity in neuronal cells caused by cerebrospinal fluid from pneumococcal and gram-negative meningitis

To identify neurotoxic factors in meningitis, a neuronal cell line (HN33.1) was exposed to cerebrospinal fluid (CSF) obtained from rabbits with pneumococcal meningitis or Escherichia coli meningitis or 2 h and 6 h after meningitis was induced by proinflammatory bacterial products (pneumococcal cell walls, endotoxin). CSF from all types of meningitis induced similar degrees of cytotoxicity. When a soluble tumor necrosis factor (TNF) receptor that completely blocked TNF-mediated toxicity at 10(-7) M was used, all toxicity in meningitis caused by E. coli, endotoxin, or pneumococcal cell wall administration (2 h afterwards) was mediated by TNF. In contrast, CSF from animals with meningitis caused by live pneumococci or pneumococcal cell wall injection (6 h afterwards) retained cytotoxicity in the presence of the TNF receptor. Thus, in established pneumococcal meningitis, but not in the other forms of meningitis, TNF is not the only component toxic in this neuronal cell line.

Evaluation of the colorimetric VITEK 2 card for identification of gram-negative nonfermentative rods: comparison to 16S rRNA gene sequencing

Ninety strains of a collection of well-identified clinical isolates of gram-negative nonfermentative rods collected over a period of 5 years were evaluated using the new colorimetric VITEK 2 card. The VITEK 2 colorimetric system identified 53 (59%) of the isolates to the species level and 9 (10%) to the genus level; 28 (31%) isolates were misidentified. An algorithm combining the colorimetric VITEK 2 card and 16S rRNA gene sequencing for adequate identification of gram-negative nonfermentative rods was developed. According to this algorithm, any identification by the colorimetric VITEK 2 card other than Achromobacter xylosoxidans, Acinetobacter sp., Burkholderia cepacia complex, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia should be subjected to 16S rRNA gene sequencing when accurate identification of nonfermentative rods is of concern.

Combined endurance/resistance training early on, after a first myocardial infarction, does not induce negative left ventricular remodelling

BACKGROUND: Resistance training (RT) is safe and practicable in low-risk populations with coronary artery disease. In patients with left ventricular (LV) dysfunction after an acute ischaemic event, few data exist about the impact of RT on LV remodelling. METHODS: In this prospective, randomized, controlled study, 38 patients, after a first myocardial infarction and a maximum ejection fraction (EF) of 45%, were assigned either to combined endurance training (ET)/RT (n=17; 15 men; 54.7+/-9.4 years and EF: 40.3+/-4.5%) or to ET alone (n=21; 17 men; 57.0+/-9.6 years and EF: 41.9+/-4.9%) for 12 weeks. ET was effectuated at an intensity of 70-85% of peak heart rate; RT, between 40 and 60% of the one-repetition maximum. LV remodelling was assessed by MRI. RESULTS: No statistically significant differences between the groups in the changes of end-diastolic volume (P=0.914), LV mass (P=0.885) and EF (P=0.763) were observed. Over 1 year, the end-diastolic volume increased from 206+/-41 to 210+/-48 ml (P=0.379) vs. 183+/-44 to 186+/-52 ml (P=0.586); LV mass from 149+/-28 to 155+/-31 g (P=0.408) vs. 144+/-36 to 149+/-42 g (P=0.227) and EF from 49.1+/-12.3 to 49.3+/-12.0% (P=0.959) vs. 51.5+/-13.1 to 54.1% (P=0.463), in the ET/RT and ET groups, respectively. Peak VO2 and muscle strength increased significantly in both groups, but no difference between the groups was noticed. CONCLUSION: RT with an intensity of up to 60% of the one-repetition maximum, after an acute myocardial infarction, does not lead to a more pronounced LV dilatation than ET alone. A combined ET/RT, or ET alone, for 3 months can both increase the peak VO2 and muscle strength significantly.

Negative impact of the noseclip on high-frequency respiratory impedance measurements

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.