Electrical Stimulation Modulates High γ Activity and Human Memory Performance.

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with poor memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation

Cardioembolic but Not Other Stroke Subtypes Predict Mortality Independent of Stroke Severity at Presentation

Introduction. Etiology of acute ischemic stroke (AIS) is known to significantly influence management, prognosis, and risk of recurrence. Objective. To determine if ischemic stroke subtype based on TOAST criteria influences mortality. Methods. We conducted an observational study of a consecutive cohort of patients presenting with AIS to a single tertiary academic center. Results. The study population consisted of 500 patients who resided in the local county or the surrounding nine-county area. No patients were lost to followup. Two hundred and sixty one (52.2%) were male, and the mean age at presentation was 73.7 years (standard deviation, SD = 14.3). Subtypes were as follows: large artery atherosclerosis 97 (19.4%), cardioembolic 144 (28.8%), small vessel disease 75 (15%), other causes 19 (3.8%), and unknown 165 (33%). One hundred and sixty patients died: 69 within the first 30 days, 27 within 31–90 days, 29 within 91–365 days, and 35 after 1 year. Low 90-, 180-, and 360-day survival was seen in cardioembolic strokes (67.1%, 65.5%, and 58.2%, resp.), followed for cryptogenic strokes (78.0%, 75.3%, and 71.1%). Interestingly, when looking into the cryptogenic category, those with insufficient information to assign a stroke subtype had the lowest survival estimate (57.7% at 90 days, 56.1% at 180 days, and 51.2% at 1 year). Conclusion. Cardioembolic ischemic stroke subtype determined by TOAST criteria predicts long-term mortality, even after adjusting for age and stroke severity

Do Placebo Response Rates from Cessation Trials Inform on Strength of Addictions?

There is an implied assumption that addictions to different substances vary in strength from weak (easier to stop) to strong (harder to stop), though explicit definitions are lacking. Our hypothesis is that the strength of addictions can be measured by cessation rates found with placebo or no treatment controls, and that a weaker addiction would have a higher cessation rate than a stronger addiction. We report an overview of systematic reviews and meta-analyses of cessation trials, using randomised or quasi-randomised trials and reporting objectively-measured abstinence. The outcome for comparison was quit rates–typically the percentage of participants abstinent according to an objective test of abstinence at six months or longer. Twenty-eight cessation reviews (139,000 participants) were found. Most data came from reviews of smoking cessation in over 127,000 participants, and other reviews each covered a few thousand participants. Few reviews used data from studies shorter than three months, and almost all determined abstinence using objective measures. Cessation rates with placebo in randomised trials using objective measures of abstinence and typically over six months duration were 8% for nicotine, 18% for alcohol, 47% for cocaine, and 44% for opioids. Evidence from placebo cessation rates indicates that nicotine is more difficult to give up than alcohol, cocaine, and opioids. Tobacco is also a severe addiction, with a number of major deleterious health effects in a large number of people

Proteomic comparison of selective breeding and growth hormone transgenesis in fish:Unique pathways to enhanced growth

Open Access funded by Biotechnology and Biological Sciences Research CouncilPeer reviewedPublisher PD

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Feasibility study to assess the delivery of a lifestyle intervention (TreatWELL) for patients with colorectal cancer undergoing potentially curative treatment

Objectives To assess the feasibility of delivering and evaluating a lifestyle programme for patients with colorectal cancer undergoing potentially curative treatments.Study design Non-randomised feasibility trial.Setting National Health Service (NHS) Tayside.Participants Adults with stage I–III colorectal cancer.Intervention The programme targeted smoking, alcohol, physical activity, diet and weight management. It was delivered in three face-to-face counselling sessions (plus nine phone calls) by lifestyle coaches over three phases (1: presurgery, 2: surgical recovery and 3: post-treatment recovery).Primary outcome Feasibility measures (recruitment, retention, programme implementation, achieved measures, fidelity, factors affecting protocol adherence and acceptability).Secondary outcomes Measured changes in body weight, waist circumference, walking and self-reported physical activity, diet, smoking, alcohol intake, fatigue, bowel function and quality of life.Results Of 84 patients diagnosed, 22 (26%) were recruited and 15 (18%) completed the study. Median time for intervention delivery was 5.5 hours. Coaches reported covering most (>70%) of the intervention components but had difficulties during phase 2. Evaluation measures (except walk test) were achieved by all participants at baseline, and most

Health behaviors and their relationship with disease control in people attending genetic clinics with a family history of breast or colorectal cancer

The current work aimed to assess health behaviors, perceived risk and control over breast/colorectal cancer risk and views on lifestyle advice amongst attendees at cancer family history clinics. Participants attending the East of Scotland Genetics Service were invited to complete a questionnaire (demographic data, weight and height, health behaviors and psycho-social measures of risk and perceived control) and to participate in an in-depth interview. The questionnaire was completed by 237 (49%) of attendees, ranging from 18 to 77years (mean age 46 (&plusmn;10) years). Reported smoking rates (11%) were modest, most (54%) had a BMI&gt;25kg/m2, 55% had low levels of physical activity, 58% reported inappropriate alcohol intakes and 90% had fiber intakes indicative of a low plant diet. Regression analysis indicated that belief in health professional control was associated with higher, and belief in fatalism with poorer health behavior. Qualitative findings highlighted doubts about the link between lifestyle and cancer, and few were familiar with the current evidence. Whilst lifestyle advice was considered interesting in general there was little appetite for non-tailored guidance. In conclusion, current health behaviors are incongruent with cancer risk reduction guidance amongst patients who have actively sought advice on disease risk. There are some indications that lifestyle advice would be welcomed but endorsement requires a sensitive and flexible approach, and the acceptability of lifestyle interventions remains to be explored

Impact of cognitive stimulation on ripples within human epileptic and non-epileptic hippocampus

Background: Until now there has been no way of distinguishing between physiological and epileptic hippocampal ripples in intracranial recordings. In the present study we addressed this by investigating the effect of cognitive stimulation on interictal high frequency oscillations in the ripple range (80-250 Hz) within epileptic (EH) and non-epileptic hippocampus (NH). Methods: We analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom hippocampal activity was recorded initially during quiet wakefulness and subsequently during a simple cognitive task. Using automated detection of ripples based on amplitude of the power envelope, we analyzed ripple rate (RR) in the cognitive and resting period, within EH and NH. Results: Compared to quiet wakefulness we observed a significant reduction of RR during cognitive stimulation in EH, while it remained statistically marginal in NH. Further, we investigated the direct impact of cognitive stimuli on ripples (i.e. immediately post-stimulus), which showed a transient statistically significant suppression of ripples in the first second after stimuli onset in NH only. Conclusion: Our results point to a differential reactivity of ripples within EH and NH to cognitive stimulation