The Brain Stress System in the Neurobiology of the “Dark Side” of Addiction and Its Relation to Neurodegeneration

Addiction is a chronically relapsing disorder characterized by a compulsion to seek and take a substance of abuse, the development of dependence, and a negative emotional state when intake is stopped. Compelling evidence argues that dysregulation of the brain stress system is a key constituent of the addiction process. Through mechanisms of negative reinforcement, the stress system is posited to induce negative emotional state referred to as the ‘dark side of addiction’ as it becomes the powerful motivation for drug-seeking associated with compulsive use. Therein, the neuropharmacological actions of corticotropin-releasing factor (CRF) is posited to play a key role in the anxiety/stress-like effects of acute withdrawal, anxiety/stress-like effects of abstinence, and relapse to drug taking. In this view, the present chapter sheds a critical light on latest research developments implicating this largely neglected component of substance abuse to give insight into the neuropathology of the ‘dark side’ of addiction. Moreover, the chapter provides insight into individual vulnerability to addiction and proposes a novel treatment candidate for the disorder

Hypothalamic-Pituitary-Adrenal (HPA) Axis and Chronic Fatigue Syndrome in Older Adults: The Rehabilitation Perspectives

Chronic fatigue syndrome (CFS) is a long-term and debilitating condition that regards as a neurological disease. Its symptoms include profound physical and mental fatigue (characteristically made worse by exertion), muscle and joint pain, disturbed sleep, and both concentration and memory problems. CFS is a kind of human stress-related disorders that are characterized by alterations in hypothalamic-pituitary-adrenal (HPA) axis activity. Investigation of abnormal activity of the HPA axis in various neurological and neuropsychiatric disorders can date back at least 60 years, and its relation to CFS had been reported in the early 1990s. This chapter further disseminated updated evidence for disruption of HPA function in CFS, with the explanation on the relationship between cytokines and HPA activities. Moreover, very limited literature had addressed the importance of rehabilitation to them . This chapter addresses this gap by sharing a pilot rehabilitation outcome on a single-blinded randomized control trial with a parallel group experimental design in the application of activity scheduling (AS) program of occupational therapy for a group of community-dwelling older adults with CFS. The primary objective is to study the outcome of physical functioning of individual participants. The second objective is to study the outcome of AS on impact of caring role through assessing individual caregivers’ perceived burden in care. The third objective is to study the time that needed in taking care; individuals’ perception of enjoyment and achievement in their participated activities will be evaluated. There was a significant effect of AS on the physical functioning of participants as measured by Functional Independence Measure (FIM), as the primary outcome measure, in experimental group, with Wilk’s λ = 0.72, F (2,57) = 18.75, p < 0.001. Moreover, in secondary outcome measures, there is a significant decrease in the impact of caring role as reflected by their perceived burden as measured by the Chinese Zarit Burden Interview (CZBI) in caring for experimental group, with Wilk’s λ = 0.72, F (2,97) = 18.75, p < 0.001. Another study set out to examine the effect of time on caring activities for those recruited couples in AS group. There was significant effect of AS on caring activities with Wilk’s λ = 0.71, F (2,97) = 12.47, p < 0.001. With proper coaching and regular facilitation regarding AS, activity participation in older adults with CFS can be greatly enhanced. Behavioral intervention, such as AS, can supplement therapeutic treatment or may lead to decline in CFS symptoms

Meta-Analysis on the Effectiveness of Virtual Reality Cognitive Training (VRCT) and Computer-Based Cognitive Training (CBCT) for Individuals with Mild Cognitive Impairment (MCI)

This meta-analysis aims to assess the effectiveness of virtual reality cognitive training (VRCT) and conventional computer-based cognitive training (CBCT) in five specific cognitive domains (i.e., global cognitive function (GCF), memory (Mem), executive function (EF), language (Lang) and visuospatial skills (VS)) of individuals with mild cognitive impairment. A total of 320 studies were yielded from five electronic databases. Eighteen randomized controlled trials met the PRISMA criteria, with 10 related to VRCT and 8 related to CBCT. A random-effect model was used in determining the main effect of cognitive training in five specific cognitive domains. VRCT provided the largest effect size on VS and Lang while the smallest on EF. CBCT provided the largest effect size on Mem and Lang while the smallest on EF. VRCT and CBCT generate an opposite effect on VS. VRCT outweighs CBCT in treatment effectiveness of GCF, EF, Lang and VS. More immersive and interactive experiences in VRCT may help individuals with MCI better engage in real-life experiences, which supports skill generalization and reduces external distractions. CBCT tends to improve Mem but no definite conclusions can be made. Further investigation with more stringent research design and specific protocol are required to reach consensus about the optimum intervention regime

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

ICAR: endoscopic skull‐base surgery

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Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe