Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial.

BACKGROUND: A Tat Oyi vaccine preparation was administered with informed consent to 48 long-term HIV-1 infected volunteers whose viral loads had been suppressed by antiretroviral therapy (cART). These volunteers were randomized in double-blind method into four groups (n = 12) that were injected intradermally with 0, 11, 33, or 99 µg of synthetic Tat Oyi proteins in buffer without adjuvant at times designated by month 0 (M0), M1 and M2, respectively. The volunteers then underwent a structured treatment interruption between M5 and M7. RESULTS: The primary outcomes of this phase I/IIa clinical trial were the safety and lowering the extent of HIV RNA rebound after cART interruption. Only one undesirable event possibly due to vaccination was observed. The 33 µg dose was most effective at lowering the extent of HIV RNA and DNA rebound (Mann and Whitney test, p = 0.07 and p = 0.001). Immune responses against Tat were increased at M5 and this correlated with a low HIV RNA rebound at M6 (p = 0.01). CONCLUSION: This study suggests in vivo that extracellular Tat activates and protects HIV infected cells. The Tat Oyi vaccine in association with cART may provide an efficient means of controlling the HIV-infected cell reservoir.

Chain and conformation stability of solid-state DNA: implications for room temperature storage.

There is currently wide interest in room temperature storage of dehydrated DNA. However, there is insufficient knowledge about its chemical and structural stability. Here, we show that solid-state DNA degradation is greatly affected by atmospheric water and oxygen at room temperature. In these conditions DNA can even be lost by aggregation. These are major concerns since laboratory plastic ware is not airtight. Chain-breaking rates measured between 70 degrees C and 140 degrees C seemed to follow Arrhenius' law. Extrapolation to 25 degrees C gave a degradation rate of about 1-40 cuts/10(5) nucleotides/century. However, these figures are to be taken as very tentative since they depend on the validity of the extrapolation and the positive or negative effect of contaminants, buffers or additives. Regarding the secondary structure, denaturation experiments showed that DNA secondary structure could be preserved or fully restored upon rehydration, except possibly for small fragments. Indeed, below about 500 bp, DNA fragments underwent a very slow evolution (almost suppressed in the presence of trehalose) which could end in an irreversible denaturation. Thus, this work validates using room temperature for storage of DNA if completely protected from water and oxygen.

Enthesopathies as occupational stress markers: evidence from the upper limb.

Enthesopathies--that is, "musculo-skeletal stress markers"--are frequently used to reconstruct past lifestyles and activity patterns. Relatively little attention has been paid in physical anthropology to methodological gaps implicit in this approach: almost all methods previously employed neglect current medical insights into enthesopathies and the distinction between healthy and pathological aspects has been arbitrary. This study presents a new visual method of studying fibrocartilaginous enthesopathies of the upper limb (modified from Villotte: Bull Mém Soc Anthropol Paris n.s. 18 (2006) 65-85), and application of this method to 367 males who died between the 18th and 20th centuries, from four European identified skeletal collections: the Christ Church Spitalfields Collection, the identified skeletal collection of the anthropological museum of the University of Coimbra, and the Sassari and Bologna collections of the museum of Anthropology, University of Bologna. The analysis, using generalized estimating equations to model repeated binary outcome variables, has established a strong link between enthesopathies and physical activity: men with occupations involving heavy manual tasks have significantly (P-value < 0.001) more lesions of the upper limbs than nonmanual and light manual workers. Probability of the presence of an enthesopathy also increases with age and is higher for the right side compared with the left. Our study failed to distinguish significant differences between the collections when adjusted for the other effects. It appears that enthesopathies can be used to reconstruct past lifestyles of populations if physical anthropologists: 1) pay attention to the choice of entheses in their studies and 2) use appropriate methods.

Simultaneous assessment of average fragment size and amount in minute samples of degraded DNA.

There is currently no method allowing routine characterization of minute amounts of degraded DNA samples such as those encountered in forensic science, archived tissues, ancient DNA, extracellular or stool DNA, and processed food. Here we describe and directly validate such a method based, on the one hand, on a generalized DNA random fragmentation model and, on the other, on two quantitative polymerase chain reaction (PCR) experiments using two different target sizes. The model also makes it possible to determine the minimum sample amount, the minimum mass average fragment size, and the maximum degradation time necessary to obtain a positive PCR.

Control of extended-spectrum ß-lactamase-producing Enterobacteriaceae nosocomial acquisition in an intensive care unit: A time series regression analysis.

BACKGROUND: This study was undertaken to determine the temporal relationship between implementation of different interventions in an intensive care unit (ICU) and control of endemic nosocomial acquisition of extended-spectrum ß-lactamase Enterobacteriaceae (ESBLE). METHODS: This was a prospective observational study with time-series analysis of the monthly incidence of ESBLE and its predictors. In November 2007, after a 14-month baseline period, an intervention consisting of restriction of third-generation cephalosporins (3 GC) and increased use of alcohol-based hand rubs was implemented. In January 2008, an increased health care worker (HCW):patient ratio was also implemented. In March 2010, the ICU was closed, and patients were moved to a clean ICU. RESULTS: The first intervention resulted in global reduction in 3 GC and increased use of alcohol-based hand rub. A significant change in ESBLE incidence was observed in a full segmented univariate regression analysis (mean change in level, -0.91 ± 0.19; P < .0001). After ICU closure, there was a dramatic reduction in ESBLE acquisition. According to the multivariate model, the ICU closure was the main protective factor. Before ICU closure, an increase in the HCW:patient ratio of 0.1 point tended to be associated with a decreased risk of ESBLE acquisition (relative risk, 0.28; 95% confidence interval, 0.06-1.25; P = .09). CONCLUSIONS: This study shows that ICU closure was associated with, but not necessarily the reason for, control of ESBLE cross-transmission in a nonoutbreak setting. Environmental ESBE sources may play a role in cross-transmission.