MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

Background: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods: Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p. 0.50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference was not significant (p = 0.27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0.30). Interpretation: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression.

The place of (explicit) grammar within the methods and approaches of foreign language teaching: in the north, in the centre or on the margins?

This article analyzes the role that has been attributed to grammar throughout the history of foreign language teaching, with special emphasis on methods and approaches of the twentieth century. In order to support our argument, we discuss the notion of grammar by proposing a conceptual continuum that includes the main meanings of the term which are relevant to our research. We address as well the issue of "pedagogical grammar" and consider the position of grammar in the different approaches of the "era of the methods" and the current "post-method condition" in the field of language teaching and learning. The findings presented at the end of the text consist of recognizing the central role that grammar has played throughout the history of the methods and approaches, where grammar has always been present by the definition of the contents' progression. The rationale that we propose for this is the recognition of the fact that the dissociation between what is said and how it is said can not be more than theoretical and, thus, artificial.

Comparison between the C5 or C6-Cz electrode assembly and C3 or C4-Cz assembly for transcranial electric motor activation of muscular response of the contralateral facial nerve

We used an assembly of electrodes C3 and C4-Cz in order to activate the motor cortical area of the corticobulbar tract to elucidate the motor-evoked potential of the contralateral mentalis muscle. We compared this setup to that of an assembly with electrodes C5 or C6-Cz using a train of electrical pulses and a single electrical pulse. This analysis was made in 23 consecutive patients who underwent several varied surgeries and were prospectively operated on at Santa Paula Hospital between January and June 2011. The results showed that the assembly with C5 or C6-Cz produced a multisynaptic motor-evoked potential in the contralateral mentalis muscle in 86.9 % of the patients, whereas 82.6 % of patients stimulated at points C3 or C4-Cz presented the same response. However, both assemblies showed similar behavior with the use of a single electrical pulse for peripheral contralateral nerve stimulation. We concluded that the C5 or C6-Cz assembly was similar to C3 or C4-Cz in obtaining a multisynaptic response in the contralateral mentalis muscle, although it required less intensive stimulation than the C3 or C4- Cz assembly.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

Therapeutic ultrasound for osteoarthritis of the knee or hip

Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Therapeutic ultrasound is one of several physical therapy modalities suggested for the management of pain and loss of function due to osteoarthritis (OA).

Enamel matrix protein adsorption to root surfaces in the presence or absence of human blood

Background: The clinical use of an enamel matrix derivative (EMD) has been shown to promote formation of new cementum, periodontal ligament (PDL), and bone and to significantly enhance the clinical outcomes after regenerative periodontal surgery. It is currently unknown to what extent the bleeding during periodontal surgery may compete with EMD adsorption to root surfaces. The aim of this study is to evaluate the effect of blood interactions on EMD adsorption to root surfaces mimicking various clinical settings and to test their ability to influence human PDL cell attachment and proliferation. Methods: Teeth extracted for orthodontic reasons were subjected to ex vivo scaling and root planing and treated with 24% EDTA, EMD, and/or human blood in six clinically related settings to determine the ability of EMD to adsorb to root surfaces. Surfaces were analyzed for protein adsorption via scanning electron microscopy and immunohistochemical staining with an anti-EMD antibody. Primary human PDL cells were seeded on root surfaces and quantified for cell attachment and cell proliferation. Results: Plasma proteins from blood samples altered the ability of EMD to adsorb to root surfaces on human teeth. Samples coated with EMD lacking blood demonstrated a consistent even layer of EMD adsorption to the root surface. In vitro experiments with PDL cells demonstrated improved cell attachment and proliferation in all samples coated with EMD (irrespective of EDTA) when compared to samples containing human blood. Conclusion: Based on these findings, it is advised to minimize blood interactions during periodontal surgeries to allow better adsorption of EMD to root surfaces.

Doxycycline for osteoarthritis of the knee or hip

Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration. This is an update of a Cochrane review first published in 2009.

Meta-analysis: chondroitin for osteoarthritis of the knee or hip

BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

The polytraumatized or multiply injured child

10.1 In the severely injured infant and child the following age-specific facts should be kept in mind: ■ Larger head to body weight ratio (head often exposed to injury, neck injury) ■ Larger body surface area to body volume ratio (hypothermia) ■ More elastic thoracic wall (internal injury possible without external signs) ■ Thinner abdominal wall where abdominal organs are below the rib cage (liver, spleen injury) ■ Smaller total blood volume ■ Narrow airways ■ Long compensation of blood loss by tachycardia followed by rapid decompensation of circulatory status if left untreated 10.2 Child abuse is frequent: about 3%–7% of children under 18 years suffer from child abuse in some manner. The incidence and prevalence depend on the development of a country’s social service agencies and on the level of health professionals’ awareness of the problem. The estimated number of unreported cases is high. Child abuse affects children of all socioeconomic, ethnic, and religious boundaries. There is no gender preponderance. It occurs at any age, but infants and toddler have a higher risk than older children.