Effect of a single dose of pregabalin on herpes zoster pain

<p>Abstract</p> <p>Background</p> <p>The effect of pregabalin on acute herpes zoster pain has not been previously evaluated.</p> <p>Methods</p> <p>In a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster.</p> <p>Results</p> <p>Over 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant.</p> <p>Conclusions</p> <p>Compared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00352651">NCT00352651</a></p

Combining Classical and Molecular Approaches Elaborates on the Complexity of Mechanisms Underpinning Anterior Regeneration

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration

AdS5AdS_{5} black hole at N=2 supergravity

In this paper, we consider the charged non-extremal black hole at five dimensional N = 2 supergravity. We study thermodynamics of AdS_{5} black hole with three equal charges (q_{1} = q_{2} = q_{3} = q). We obtain Schrodinger like equation and discuss the effective potential. Then, we consider the case of the perturbed dilaton field background and find presence of odd coefficients of the wave function. Also we find that the higher derivative corrections have no effect on the first and second even coefficients of the wave function.Comment: 17 pages, 4 figures. Published versio

Transplacental Transmission of Leishmania infantum as a Means for Continued Disease Incidence in North America

Dogs are a favored feeding source for sand flies that transmit human L. infantum infection. Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with over 20% of at-risk Foxhounds infected. Although classically Leishmania is transmitted by infected sand flies which exist in the United States, no role has yet been determined for vector-borne transmission. Means of ongoing L. infantum transmission in U.S. dogs is unknown. Possibilities include transplacental and horizontal/venereal transmission. Aims for this study were to establish whether transplacental transmission occurred in Leishmania-infected U.S. dogs and determine the effect of this transmission on immune recognition of Leishmania. This novel report describes wide-spread infection as identified by kqPCR in 8 day-old pups born to a naturally-infected, seropositive U.S. dog with no travel history. This is the first report of transplacental transmission of L. infantum in naturally-infected dogs in North America. Evidence that mom-to-pup transmission of ZVL may continue disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL. Determining frequency of vertical transmission and incorporating canine sterilization with vector control may have a more significant impact on ZVL transmission to people in endemic areas than current control efforts

Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006–2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05–1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation

The influence of soil communities on the temperature sensitivity of soil respiration

Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.

IMPORTANCE: Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear. OBJECTIVE: To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023. EXPOSURE: LTL. MAIN OUTCOMES AND MEASURES: Cardiovascular imaging traits and HF. RESULTS: Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF

Whey Protein Supplementation Post Resistance Exercise in Elderly Men Induces Changes in Muscle miRNA's Compared to Resistance Exercise Alone

Progressive muscle loss with aging results in decreased physical function, frailty, and impaired metabolic health. Deficits in anabolic signaling contribute to an impaired ability for aged skeletal muscle to adapt in response to exercise and protein feeding. One potential contributing mechanism could be exerted by dysregulation of microRNAs (miRNAs). Therefore, the aim of this study was to determine if graded protein doses consumed after resistance exercise altered muscle miRNA expression in elderly men. Twenty-three senior men (67.9 ± 0.9 years) performed a bout of resistance exercise and were randomized to consume either a placebo, 20 or 40 g of whey protein (n = 8, n = 7, and n = 8, respectively). Vastus lateralis biopsies were collected before, 2 and 4 h after exercise. Expression of 19 miRNAs, previously identified to influence muscle phenotype, were measured via RT-PCR. Of these, miR-16-5p was altered with exercise in all groups (p = 0.032). Expression of miR-15a and-499a increased only in the placebo group 4 h after exercise and miR-451a expression increased following exercise only in the 40 g whey supplementation group. Changes in p-P70S6KThr389 and p-AktSer473 following exercise were correlated with alterations in miR-208a and-499a and-206 expression, irrespective of protein dose, suggesting a possible role for miRNA in the regulation of acute phosphorylation events during early hours of exercise recovery