Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Plasma REST: A novel candidate biomarker of Alzheimer\u27s disease is modified by psychological intervention in an at-risk population

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain’s stress response. It is reduced in conditions of stress and Alzheimer’s disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention—mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Test-retest reliability of a 16.1 km time trial in trained cyclists using the CompuTrainer ergometer

Laboratory based cycling time trials (TT) are widely used by both researchers and practitioners, as a method of assessing cycling performance in a controlled environment. Assessments of performance often use TT durations or distances between 20 min and one hour and in the UK the 10 mile (16.1 km) TT is the most frequently used race distance for trained cyclists. The 16.1 km TT has received relatively minimal, but increased attention as a performance criterion in the literature. Therefore, the aim of this study was to assess the reliability of 16.1 km TT performance in a large cohort of trained cyclists using the CompuTrainer cycling ergometer. Trained male cyclists (n = 58, mean±SD age 35±7 yr, height 179±6 cm, weight 79.1±9.4 kg, VO2max. 56.6±6.6 ml.kg.min-1, PPO 365±37 W) performed an initial incremental exercise test to determine PPO and VO2max. The participants then performed two 16.1 km TT on a CompuTrainer cycle ergometer separated by 3-7 days. Differences in time, power output and speed were determined using a Wilcoxon signed ranks or paired t-tests. Reproducibility of the TT performance measures was performed using the coefficient of variation (CV), intraclass correlations, and typical error (TE). There were no differences between any of the performance criteria for the whole cohort (Mean difference = 0.06 min, 0.09 km.h-1, 1.5 W, for time, mean speed and power respectively) between TT1 and TT2. All TT performance data were very reproducible (CV range = 1.1-2.7%) and demonstrated trivial or small TE. The slower cyclists demonstrated marginally lower reliability (CV range = 1.3-3.2%) compared to the fastest group (CV range = 0.7-2.0%). The 16.1 km TT on the CompuTrainer represents a very reliable performance criterion for trained cyclists. Interpretation of test-retest performance outcomes should be performed in the context of the TE of each performance indicator

Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback

The provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception. Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; 1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, 3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and 4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable. The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes’ performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the performance beliefs of trained individuals beyond the acute setting

Liverpool Telescope 2: beginning the design phase

The Liverpool Telescope is a fully robotic 2-metre telescope located at the Observatorio del Roque de los Muchachos on the Canary Island of La Palma. The telescope began routine science operations in 2004, and currently seven simultaneously mounted instruments support a broad science programme, with a focus on transient followup and other time domain topics well suited to the characteristics of robotic observing. Work has begun on a successor facility with the working title ‘Liverpool Telescope 2’. We are entering a new era of time domain astronomy with new discovery facilities across the electromagnetic spectrum, and the next generation of optical survey facilities such as LSST are set to revolutionise the field of transient science in particular. The fully robotic Liverpool Telescope 2 will have a 4-metre aperture and an improved response time, and will be designed to meet the challenges of this new era. Following a conceptual design phase, we are about to begin the detailed design which will lead towards the start of construction in 2018, for first light ∼2022. In this paper we provide an overview of the facility and an update on progress. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Trends in Weekly Reported Net use by Children During and after Rainy Season in Central Tanzania.

The use of long-lasting insecticidal nets (LLINs) is one of the principal interventions to prevent malaria in young children, reducing episodes of malaria by 50% and child deaths by one fifth. Prioritizing young children for net use is important to achieve mortality reductions, particularly during transmission seasons. Households were followed up weekly from January through June 2009 to track net use among children under seven under as well as caretakers. Net use rates for children and caretakers in net-owning households were calculated by dividing the number of person-weeks of net use by the number of person-weeks of follow-up. Use was stratified by age of the child or caretaker status. Determinants of ownership and of use were assessed using multivariate models. Overall, 60.1% of the households reported owning a bed net at least once during the study period. Among net owners, use rates remained high during and after the rainy season. Rates of use per person-week decreased as the age of the child rose from 0 to six years old; at ages 0-23 months and 24-35 months use rates per person-week were 0.93 and 0.92 respectively during the study period, while for children ages 3 and 4 use rates per person-week were 0.86 and 0.80. For children ages 5-6 person-week ratios dropped to 0.55. This represents an incidence rate ratio of 1.67 for children ages 0-23 months compared to children aged 5-6. Caretakers had use rates similar to those of children age 0-35 months. Having fewer children under age seven in the household also appeared to positively impact net use rates for individual children. In this area of Tanzania, net use is very high among net-owning households, with no variability either at the beginning or end of the rainy season high transmission period. The youngest children are prioritized for sleeping under the net and caretakers also have high rates of use. Given the high use rates, increasing the number of nets available in the household is likely to boost use rates by older children

Hospitalization for pertussis: profiles and case costs by age

BACKGROUND: Pertussis, a highly contagious respiratory illness, affects people of all ages and can have serious clinical consequences. It has been reported that from 1997–2000, 20% of all pertussis cases required hospitalization in the US. This analysis examined demographics, case fatality rate, resource use and costs of hospital care related to pertussis by age. METHODS: ICD-9 codes (033.0, 033.9) were used to identify cases of pertussis in hospital discharge databases from roughly 1,000 US hospitals in 4 states (California, Florida, Maryland, Massachusetts). Data from 1996–1999 were examined by age group. Separate analyses were done for infants (<1 year) and children (1–11 years); however, adolescent and adult cases were combined into one group (12+ years), due to the small number of cases. Databases were used to determine demographics, health service utilization and care costs. Cost estimates include accommodations, ancillary and physician services, reported in 2002 US$. RESULTS: Of the 2,518 cases identified, 90$9,586 per stay. Children (n = 191) had a mean LOS of 3.7 and cost of $4,729; adolescents/adults (n = 61, mean age 40 years) stayed on average 3.4 days with a cost of$5,683 per hospitalization. CONCLUSION: Infants are responsible for the bulk of hospitalizations and generate higher inpatient costs. Costly hospital care occurs, however, in patients with pertussis at all ages

Inability to predict postpartum hemorrhage: insights from Egyptian intervention data

<p>Abstract</p> <p>Background</p> <p>Knowledge on how well we can predict primary postpartum hemorrhage (PPH) can help policy makers and health providers design current delivery protocols and PPH case management. The purpose of this paper is to identify risk factors and determine predictive probabilities of those risk factors for primary PPH among women expecting singleton vaginal deliveries in Egypt.</p> <p>Methods</p> <p>From a prospective cohort study, 2510 pregnant women were recruited over a six-month period in Egypt in 2004. PPH was defined as blood loss ≥ 500 ml. Measures of blood loss were made every 20 minutes for the first 4 hours after delivery using a calibrated under the buttocks drape. Using all variables available in the patients' charts, we divided them in ante-partum and intra-partum factors. We employed logistic regression to analyze socio-demographic, medical and past obstetric history, and labor and delivery outcomes as potential PPH risk factors. Post-model predicted probabilities were estimated using the identified risk factors.</p> <p>Results</p> <p>We found a total of 93 cases of primary PPH. In multivariate models, ante-partum hemoglobin, history of previous PPH, labor augmentation and prolonged labor were significantly associated with PPH. Post model probability estimates showed that even among women with three or more risk factors, PPH could only be predicted in 10% of the cases.</p> <p>Conclusions</p> <p>The predictive probability of ante-partum and intra-partum risk factors for PPH is very low. Prevention of PPH to all women is highly recommended.</p

Maternal Infection with Trypanosoma cruzi and Congenital Chagas Disease Induce a Trend to a Type 1 Polarization of Infant Immune Responses to Vaccines

Vaccines are of crucial importance to prevent morbidity and mortality due to infectious diseases in childhood. A modulation of the fetal/neonatal immune system (considered immature) toward Th1 or Th2 dominance could modify responses to vaccines administered in early life. T. cruzi is the agent of Chagas' disease, in Latin America currently infecting about 2 million women at fertile ages who are susceptible to transmitting the parasite to their fetus. In previous studies we showed that T. cruzi-infected mothers can induce a pro-inflammatory environment in their uninfected neonates (M+B−), whereas congenitally infected newborns (M+B+) are able to develop a pro-Th1 parasite-specific T cell response. In the present study, we analysed the cellular and/or antibody responses to Bacillus Calmette Guerin (BCG), hepatitis B birus (HBV), diphtheria and tetanus vaccines in 6- to 7-month-old infants living in Bolivia. M+B− infants produced more IFN-γ in response to BCG, whereas M+B+ infants developed a stronger IFN-γ response to hepatitis B, diphtheria and tetanus vaccines and enhanced antibody production to HBs antigen. These results show that both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period and that T. cruzi infection in early life tends to favour type 1 immune responses to vaccinal antigens