HIV-1 p24 may persist during long-term highly active antiretroviral therapy, increases little during short treatment breaks, and its rebound after treatment stop correlates with CD4(+) T cell loss

The dynamics of HIV-1 RNA during structured treatment interruptions (STIs) are well established, but little is known about viral proteins like p24. We studied 65 participants of an STI trial. Before the trial, continuous highly active antiretroviral therapy (HAART) had suppressed their viral load to <50 copies/mL during 6 months. They then interrupted HAART during weeks 1 through 2, 11 through 12, 21 through 22, 31 through 32, and 41 through 52. The p24 was measured by boosted enzyme-linked immunosorbent assay of plasma pretreated by efficient virus disruption and heat denaturation. At time point 0, p24 was measurable in 22 patients (34%), who had maintained a viral load <50 copies/mL for 25.4 months (median, range: 6.2-38.9 months) under HAART. Viral rebounds during 2-week STIs led to a mean p24 increase of only 0.08 to 0.19 log10 (ie, 20%-60%). Pre-HAART viral load and p24 at time 0 independently predicted p24 rebounds during the 4 2-week STIs. The p24 at time 0 and HIV-1 RNA rebound during weeks 41 through 52 independently determined the concomitant p24 rebound. An increase of p24 but not viral load during the first 8 weeks of the long STI correlated significantly with concomitant CD4(+) T cell loss. Persisting p24 despite successful HAART may reflect virus replication in reservoirs not represented by plasma viral load and has implications for the concept of therapeutic vaccination.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

1,25-(OH)2-16ene-23yne-D3 reduces secondary hyperparathyroidism in uremic rats with little calcemic effect

To compare the effects of vitamin D analogs versus calcitriol on serum levels of Ca, P and parathyroid hormone (PTH). A compound better than calcitriol should increase the Ca x P product less than calcitriol for an equivalent decrease in PTH levels.

Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era

The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

Amplified inception of European Little Ice Age by sea ice-ocean-atmosphere feedbacks

The inception of the Little Ice Age (~1400–1700 AD) is believed to have been driven by an interplay of external forcing and climate system internal variability. While the hemispheric signal seems to have been dominated by solar irradiance and volcanic eruptions, the understanding of mechanisms shaping the climate on a continental scale is less robust. In an ensemble of transient model simulations and a new type of sensitivity experiments with artificial sea ice growth, the authors identify a sea ice–ocean–atmosphere feedback mechanism that amplifies the Little Ice Age cooling in the North Atlantic–European region and produces the temperature pattern suggested by paleoclimatic reconstructions. Initiated by increasing negative forcing, the Arctic sea ice substantially expands at the beginning of the Little Ice Age. The excess of sea ice is exported to the subpolar North Atlantic, where it melts, thereby weakening convection of the ocean. Consequently, northward ocean heat transport is reduced, reinforcing the expansion of the sea ice and the cooling of the Northern Hemisphere. In the Nordic Seas, sea surface height anomalies cause the oceanic recirculation to strengthen at the expense of the warm Barents Sea inflow, thereby further reinforcing sea ice growth. The absent ocean–atmosphere heat flux in the Barents Sea results in an amplified cooling over Northern Europe. The positive nature of this feedback mechanism enables sea ice to remain in an expanded state for decades up to a century, favoring sustained cold periods over Europe such as the Little Ice Age. Support for the feedback mechanism comes from recent proxy reconstructions around the Nordic Seas.

Energy harvesting from the cardiovascular system, or how to get a little help from yourself

Human energy harvesting is envisioned as a remedy to the weight, the size, and the poor energy density of primary batteries in medical implants. The first implant to have necessarily raised the idea of a biological power supply was the pacemaker in the early 1960s. So far, review articles on human energy harvesting have been rather unspecific and no tribute has been given to the early role of the pacemaker and the cardiovascular system in triggering research in the field. The purpose of the present article is to provide an up-to-date review of research efforts targeting the cardiovascular system as an alternative energy source for active medical implants. To this end, a chronological survey of the last 14 most influential publications is proposed. They include experimental and/or theoretical studies based on electromagnetic, piezoelectric, or electrostatic transducers harnessing various forms of energy, such as heart motion, pressure gradients, and blood flow. Technical feasibility does not imply clinical applicability: although most of the reported devices were shown to harvest an interesting amount of energy from a physiological environment, none of them were tested in vivo for a longer period of time.Human energy harvesting is envisioned as a remedy to the weight, the size, and the poor energy density of primary batteries in medical implants. The first implant to have necessarily raised the idea of a biological power supply was the pacemaker in the early 1960s. So far, review articles on human energy harvesting have been rather unspecific and no tribute has been given to the early role of the pacemaker and the cardiovascular system in triggering research in the field. The purpose of the present article is to provide an up-to-date review of research efforts targeting the cardiovascular system as an alternative energy source for active medical implants. To this end, a chronological survey of the last 14 most influential publications is proposed. They include experimental and/or theoretical studies based on electromagnetic, piezoelectric, or electrostatic transducers harnessing various forms of energy, such as heart motion, pressure gradients, and blood flow. Technical feasibility does not imply clinical applicability: although most of the reported devices were shown to harvest an interesting amount of energy from a physiological environment, none of them were tested in vivo for a longer period of time.

Multiple tree-ring proxies (earlywood width, latewood width and δ13C) from pedunculate oak (Quercus robur L.), Hungary

The aim of this study was to analyse the effects of climatic factors (i.e. monthly mean temperature and total precipitation) on radial growth (earlywood width, latewood width, and total ringwidth) and on latewood stable carbon isotope composition in a pedunculate oak (Quercus robur L) stand in northeastern Hungary. Earlywood widths showed the weakest common variance and lack of statistically significant relationship to monthly precipitation and temperature. Latewood width showed the strongest common chronological signal. Correlation analysis with the monthly climate series pointed out the strongest positive/negative correlation with June precipitation for latewood width/stable carbon isotope ratio. These parameters shared the strongest climatic response also for seasonal scale since the highest correlation coefficients, 0.49 and -0.62 for latewood width and stable carbon isotope ratio, respectively, were obtained for both with a 10-month precipitation total (from previous November to current August of the growing season). A combined parameter, derived as difference between latewood width and stable carbon isotope indices showed improved statistical relationship compared to the hydroclimatic calibration target both for local and regional spatial scales. Spatial correlation analysis indicated that the hydroclimatic signal encoded in these moisture sensitive tree-ring parameters from Bakta Forest is expected to be representative for the northeastern Carpathians and for the large part of the Great Hungarian Plain. In addition, the hydroclimatic signal of latewood width chronology was compared to three independent records. Results showed that neither the strength nor the rank of the similarity of the local hydroclimate signals were stable throughout the past two centuries. Future palaeo(hydro)climatological efforts targeting the Carpathian(-Balkan) region are recommended to track carefully the spatial domains for which a given, local, proxy-derived hydroclimate reconstruction might provide useful information.