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Background. Human immunodeficiency virus type 1 (HIV-1) DNA dynamics during long-term antiretroviral therapy (ART) are not defined. Methods. Blood mononuclear cells obtained during 7–12 years of effective ART were assayed for total HIV-1 DNA and 2-long terminal repeat (LTR) circles by quantitative polymerase chain reaction (qPCR). Slopes of HIV-1 DNA were estimated by participant-specific linear regressions. Plasma was assayed for residual viremia (HIV-1 RNA) by qPCR. Results. Thirty participants were studied. HIV-1 DNA decreased significantly from years 0–1 and 1–4 of ART with median decay slopes of -0.86 (interquartile range, -1.05, -0.59) and -0.11 (-0.17, -0.06) log 10 (copies/10 6 CD4+ T-cells)/year, respectively (P < .001). Decay was not significant for years 4–7 (-0.02 [-0.06, 0.02]; P = .09) or after year 7 of ART (-0.006 [-0.030, 0.015]; P = .17). All participants had detectable HIV-1 DNA after 10 years (median 439 copies/10 6 CD4+ T-cells; range: 7–2074). Pre-ART HIV-1 DNA levels were positively associated with pre-ART HIV-1 RNA levels (Spearman = 0.71, P < .001) and with HIV-1 DNA at years 4, 7, and 10 on ART (Spearman ≥ 0.75, P < .001). No associations were found (P ≥ .25) between HIV-1 DNA slopes or levels and % activated CD8+ T-cells (average during years 1–4) or residual viremia (n = 18). 2-LTR circles were detected pre-ART in 20/29 and in 8/30 participants at last follow-up. Conclusions. Decay of HIV-1 DNA in blood is rapid in the first year after ART initiation (86% decline), slows during years 1–4 (23% decline/year), and subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+ T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA persistence require further elucidation. Clinical Trials Registration. NCT00001137.

Local vibration (LV) has been recently validated as an efficient training method to improve muscle strength. Understanding the acute effects may help elucidate the mechanism(s). This study aimed to investigate the effects of a single bout of prolonged LV on knee extensor force production and corticospinal responsiveness of vastus lateralis (VL) and rectus femoris (RF) muscles in healthy young and old adults. Across two visits, 23 adult subjects (20-75 years old) performed pre- and post-test measurements, separated by 30-min of either rest (control; CON) or LV. Maximal voluntary contraction (MVC) force was assessed and transcranial magnetic stimulation (TMS) was used to evaluate cortical voluntary activation (VA ) as well as the motor evoked potential (MEP) and silent period (SP). In 11 young adults, thoracic electrical stimulation was used to assess the thoracic motor evoked potential (TMEP). Although MVC decreased after both CON (-6.3 ± 4.4%, = 0.01) and LV (-12.9 ± 7.7%, < 0.001), the MVC loss was greater after LV ( = 0.001). Normalized maximal electromyographic (EMG) activity decreased after LV for both VL (-25.1 ± 10.7%) and RF (-20.9 ± 16.5%; < 0.001), while it was unchanged after CON ( = 0.32). For RF, the TMEP and MEP/TMEP ratio decreased ( = 0.01) and increased ( = 0.01) after LV, respectively. Both measures were unchanged for VL ( = 0.27 and = 0.15, respectively). No changes were reported for TMS-related parameters. These results confirm our hypothesis that modulations within the central nervous system would accompany the significant reduction of maximal voluntary force. A reduced motoneuron excitability seems to explain the decreased MVC after prolonged LV, as suggested by reductions in maximal EMG (all subjects) and TMEP area (data from 11 young subjects). A concomitant increased cortical excitability seems to compensate for lower excitability at the spinal level.

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1 G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies.

PurposeThe effect of trail running competitions on cost of running (Cr) remains unclear and no study has directly examined the effect of distances in similar conditions on Cr. Accordingly, the aims of this study were to (i) assess the effect of trail running races of 40–170 km on Cr and (ii) to assess whether the incline at which Cr is measured influences changes in Cr.MethodsTwenty trail runners completed races of < 100 km (SHORT) and 26 trail runners completed races of > 100 km (LONG) on similar courses and environmental conditions. Oxygen uptake, respiratory exchange ratio, ventilation, and blood lactate were measured before and after the events on a treadmill with 0% (FLAT) and 15% incline (UH) and Cr was calculated.ResultsCr increased significantly after SHORT but not LONG races. There was no clear relationship between changes in Cr and changes in ventilation or blood lactate. There was a significant correlation (r = 0.75, p < 0.01) between changes in FLAT and UH Cr, and the change in Cr was not affected by the incline at which Cr was measured.ConclusionThe distance of the trail running race, but not the slope at which it is measured, influence the changes in Cr with fatigue. The mechanism by which Cr increases only in SHORT is not related to increased cost of breathing.

Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4⁺T cells. Some of these CD4⁺T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4⁺ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4⁺T cells can be a reservoir of infectious HIV-1.

BACKGROUNDThe inability to quantify sexual exposure to HIV limits the power of HIV prevention trials of vaccines, microbicides, and preexposure prophylaxis in women. We investigated the detection of HIV-1 and Y chromosomal (Yc) DNA in vaginal swabs from 83 participants in the HPTN 035 microbicide trial as biomarkers of HIV exposure and unprotected sexual activity. METHODSOne hundred forty-three vaginal swabs from 85 women were evaluated for the presence of Yc DNA (Quantifiler Duo DNA quantification kit; Applied Biosystems) and total HIV-1 DNA (single-copy in-house quantitative polymerase chain reaction assay). Y DNA detection was paired with self-reported behavioral data with regard to recent coitus (≤1 week before collection) and condom usage (100% vs. <100% compliance). RESULTSYc DNA was detected in 62 (43%) of 143 swabs. For the 126 visits at which both behavioral data and swabs were collected, Yc DNA was significantly more frequent in women reporting less than 100% condom usage (odds ratio, 10.69; 95% confidence interval, 2.27–50.32; P = 0.003). Notably, 27 (33%) of 83 swabs from women reporting 100% condom usage were positive for Yc DNA. HIV DNA was only detected in swabs collected postseroconversion. CONCLUSIONSThe use of Yc DNA in HIV prevention trials could reliably identify subgroups of women who have unprotected sexual activity and could provide valuable exposure-based estimates of efficacy.

High-risk human papillomaviruses (HPV) are largely implicated in the carcinogenesis of cervical carcinomas. Their role in bronchopulmonary carcinomas is still unclear. In the present study, we have explored 218 fresh frozen lung tumours for the presence of HPV with the Roche line blot assay and for the expression of mRNAs encoding E6 oncoprotein in HPV positive tumours. Only four samples were positive for HPV detection, one poorly differentiated squamous cell carcinoma and three large cell carcinomas. E6 mRNA was undetectable in these four samples. Our data confirm the low prevalence of HPV in lung carcinomas in Western European countries and do not plead in favour of a carcinogenic role for HPV in these carcinomas.