Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APPNL-G-F mice before prominent plaque deposition

Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer's disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APPNL-G-F knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APPNL-G-F mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APPNL mice (APP Swedish) at 3, 7 and 10 months. Mice were subjected to a test battery that referred to clinical AD symptoms, comprising cage activity, open field, elevated plus maze, social preference and novelty test, and spatial learning, reversal learning and spatial reference memory performance. Our assessment confirmed that behavior at these early ages was largely unaffected in these mice in accordance with previous reports, with some subtle behavioral changes, mainly in social and anxiety-related test performance. Resting-state functional MRI (rsfMRI) assessed connectivity between hippocampal and prefrontal regions with an established role in flexibility, learning and memory. Increased prefrontal-hippocampal network synchronicity was found in 3-month-old APPNL-G-F mice. These functional changes occurred before prominent amyloid plaque deposition

Anxiety in Autism Spectrum Disorder (ASD) : the influence of executive and sensory processing dysfunctions

Ph. D. Thesis.Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with difficulties with social communication and the presence of restricted and repetitive behaviours. There is significant heterogeneity of symptom profiles within the disorder. Anxiety is very common in individuals with ASD. Previous research suggests associations between executive function deficits and sensory processing atypicalities and anxiety in ASD, though neither relationship has been explored in detail. Aims: To examine the putative relationships between anxiety, executive function difficulties and sensory processing atypicalities in children with ASD, taking into account potential heterogeneity within the sample. Method: Thirty six families with a child with ASD were recruited. The children completed an anxiety questionnaire and standardised assessments of executive function. Parents completed questionnaire about their child’s anxiety, sensory processing difficulties and autism severity. 22 parents completed a follow-up study of their child’s anxiety, everyday executive function and repetitive behaviours. Correlational analysis and cluster analysis were used to examine the data. Results: Anxiety scores were high and remained stable over a twenty month period. No significant associations were found between objective measures of executive function difficulties and anxiety, though parent reported child executive difficulties were associated with heightened parent reported child anxiety.High anxiety was associated with sensory processing atypicalities, and higher levels of ASD severity. Importantly, cluster analysis revealed distinct subgroups of children in relation to anxiety, sensory and executive profiles, illustrating heterogeneity within the sample. Conclusions: The findings supports previous research that anxiety is high in children with ASD and remains high over time and is associated with sensory processing atypicalities. The relationship between executive function and anxiety varied as a function of the source of the data. Cluster analysis illustrates the importance of considering heterogeneity in ASD. Implications for clinical practice and future research are discussed.Ministry of Health Malaysi

Report of the Surgeon General

In 1964, the first Surgeon General's report on the effects of smoking on health was released. In the nearly 50 years since, extensive data from thousands of studies have consistently substantiated the devastating effects of smoking on the lives of millions of Americans. Yet today in the United States, tobacco use remains the single largest preventable cause of death and disease for both men and women. Now, this 2010 report of the Surgeon General explains beyond a shadow of a doubt how tobacco smoke causes disease, validates earlier findings, and expands and strengthens the science base. Armed with this irrefutable data, the time has come to mount a full-scale assault on the tobacco epidemic. More than 1,000 people are killed every day by cigarettes, and one-half of all long-term smokers are killed by smoking-related diseases. A large proportion of these deaths are from early heart attacks, chronic lung diseases, and cancers. For every person who dies from tobacco use, another 20 Americans continue to suffer with at least one serious tobacco-related illness. But the harmful effects of smoking do not end with the smoker. Every year, thousands of nonsmokers die from heart disease and lung cancer, and hundreds of thousands of children suffer from respiratory infections because of exposure to secondhand smoke. There is no risk-free level of exposure to tobacco smoke, and there is no safe tobacco product. This new Surgeon General's report describes in detail the ways tobacco smoke damages every organ in the body and causes disease and death. We must build on our successes and more effectively educate people about the health risks of tobacco use, prevent youth from ever using tobacco products, expand access to proven cessation treatments and services, and reduce exposure to secondhand smoke. Putting laws and other restrictions in place, including making tobacco products progressively less affordable, will ultimately lead to our goal of a healthier America by reducing the devastating effects of smoking. This 2010 Surgeon General's report represents another important step in the developing recognition, both in this nation and around the world, that tobacco use is devastating to public health. Past investments in research and in comprehensive tobacco control programs--combined with the findings presented by this new report--provide the foundation, evidence, and impetus to increase the urgency of our actions to end the epidemic of tobacco use.CDC-INFO Pub ID 220456220456U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010.Chapter 1. Introduction, evaluation of evidence on mechanisms of disease production, and summary -- Chapter 2. The changing cigarette -- Chapter 3. Chemistry and toxicology of cigarette smoke and biomarkers of exposure and harm -- Chapter 4. Nicotine addiction: past and present -- Chapter 5. Cancer -- Chapter 6. Cardiovascular diseases -- Chapter 7. Pulmonary diseases -- Chapter 8. Reproductive and developmental effects -- Chapter 9. A vision for the future -- List of abbreviations -- List of tables and figures -- Definitions and alternative nomenclature of genetic symbols used in this report -- Index.2010704