Peptoids and methods for treating Alzheimer\u27s disease

Provided herein are peptoids capable of inhibiting or reversing amyloid .beta. (A.beta.) fibril or plaque production. The peptoids form a helical structure with three monomers per helical turn and have at least four monomers with a side-chain having an arylalkyl or aryl group. The peptoid may be achiral. Also provided are methods of using the peptoids to inhibit or reverse aggregation of A.beta. and methods of treating subjects with Alzheimer\u27s disease (AD) or slowing the progression of AD

Using GIS in a first national mapping of functional disability among older American Indians and Alaska natives from the 2000 census

BACKGROUND: Geographical information systems (GIS) have been used mainly in understanding infectious diseases and environmental threats in health research. Here, GIS was used to examine patterns of functional disability as one impact of chronic disease in American Indians and Alaska Natives. The study purpose was to create the first national mapping of functional disability for AIANs using the 2000 U.S. Census. RESULTS: American Indians and Alaska Natives over age 65 reported disability at a rate of 57.6% versus 41.9% for all people over 65 (P ≤ 0.0001). Regional differences in levels and type of disability were evident. CONCLUSION: Maps help visualize those who might otherwise be 'lost' from the data. The significance of this study is that gerontologic programs and policies are data-driven, yet there is a lack of reliable national level data from US health systems on functional disability among American Indians and Alaska Natives. One study limitation was that Census questions regarding disability differed from traditional measures of activities of daily living and instrumental activities of daily living. An immediate policy recommendation would be to incorporate standard activities of daily living and instrumental activities of daily living language into future Census for a comprehensive, linked database for the future

A comparison of HPV DNA testing and liquid based cytology over three rounds of primary cervical screening: extended follow up in the ARTISTIC trial.

BACKGROUND: The additional sensitivity of HPV testing compared with cytology could permit extended cervical screening intervals. We wished to determine, through a further (third) round of screening in the ARTISTIC trial, the protection provided by a negative baseline HPV screen compared with that of cytology over a 6 year period. METHODS: Cumulative rates of CIN2 or worse (CIN2+) and CIN3 or worse (CIN3+) were correlated with baseline HPV status and cytology. HPV was detected using the Hybrid Capture 2 (Qiagen) assay for high risk types and genotyped using the Linear Array (Roche) and Papillocheck (Greiner) assays. LBC was performed using ThinPrep (Hologic). FINDINGS: Round 3 included 8,873 women of whom 6,337 had been screened in both rounds 1 and 2 and 2,536 had not been screened since round 1. The median duration of follow-up was 72.7 months. The cumulative rate of CIN2+ over three rounds was 3.88% (95%CI 3.59%, 4.17%) overall; 2.39% in round 1, 0.78% in round 2 and 0.74% in round 3. Cumulative rates by baseline status were 20.53% (95%CI 19.04%, 22.08%) for abnormal cytology, 20.12% (95%CI 18.68%, 21.61%) for HPV detection, 1.41% (95%CI 1.19%, 1.65%) for negative cytology and 0.87% (95%CI 0.70%, 1.06%) for a negative HPV test. In HPV negative women aged over 50 the cumulative rate was 0.16% (95%CI 0.07%, 0.34%). Women who were HPV positive/cytology negative at entry had a cumulative CIN2+ rate of 7.73% (95%CI 6.29%, 9.36%) over 6 years, twice the overall rate. INTERPRETATION: A negative HPV test was significantly more protective than normal cytology over three rounds. The findings of this extension of ARTISTIC suggest that the screening interval could be extended to 6 years if HPV testing replaced cytology as the primary screening test

Obtaining accurate glucose measurements from wild animals under field conditions:comparing a hand held glucometer with a standard laboratory technique in grey seals

Glucose is an important metabolic fuel and circulating levels are tightly regulated in most mammals, but can drop when body fuel reserves become critically low. Glucose is mobilized rapidly from liver and muscle during stress in response to increased circulating cortisol. Blood glucose levels can thus be of value in conservation as an indicator of nutritional status and may be a useful, rapid assessment marker for acute or chronic stress. However, seals show unusual glucose regulation: circulating levels are high and insulin sensitivity is limited. Accurate blood glucose measurement is therefore vital to enable meaningful health and physiological assessments in captive, wild or rehabilitated seals and to explore its utility as a marker of conservation relevance in these animals. Point-of-care devices are simple, portable, relatively cheap and use less blood compared with traditional sampling approaches, making them useful in conservation-related monitoring. We investigated the accuracy of a hand-held glucometer for ‘instant’ field measurement of blood glucose, compared with blood drawing followed by laboratory testing, in wild grey seals (Halichoerus grypus), a species used as an indicator for Good Environmental Status in European waters. The glucometer showed high precision, but low accuracy, relative to laboratory measurements, and was least accurate at extreme values. It did not provide a reliable alternative to plasma analysis. Poor correlation between methods may be due to suboptimal field conditions, greater and more variable haematocrit, faster erythrocyte settling rate and/or lipaemia in seals. Glucometers must therefore be rigorously tested before use in new species and demographic groups. Sampling, processing and glucose determination methods have major implications for conclusions regarding glucose regulation, and health assessment in seals generally, which is important in species of conservation concern and in development of circulating glucose as a marker of stress or nutritional state for use in management and monitoring

Somatic acupoint stimulation for cancer-related sleep disturbance: A systematic review of randomized controlled trials

Aim. The aim of this systematic review was to analyze and synthesize available evidence for the effects of somatic acupoint stimulation (SAS) on cancer-related sleep disturbance in adults with cancer. Methods. Nine databases and four clinical trial registries were searched from their inception to July 2019 to identify potential articles and registered trials. Two authors independently extracted data and appraised the methodological quality of the included studies. The included studies could not be subjected to meta-analysis due to the significant variations in SAS intervention protocols and outcome measurement instruments. This systematic review therefore reported the results of the included trials narratively. Results. Seven studies were identified, which involved 906 cancer patients. SAS protocols varied across trials without an optimal evidence-based standard intervention protocol to manage cancer-related sleep disturbance. Sanyinjiao (SP6) was the most commonly selected acupoint. Manual acupuncture was typically 15–30 min in duration and was conducted once a day or once a week for a period of 1–5 weeks, whereas self-administered acupressure was typically 1–3 min in duration per point and was conducted once a day, such as during night time before going to bed, for a period of 1–5 months. The results indicated that SAS could potentially relieve cancer-related sleep disturbance and improve quality of life. Mild adverse effects were reported in three of the included studies, but none of them performed a causality analysis to clarify the association between the reported adverse events and the intervention. Conclusions. This systematic review showed that SAS is a useful approach to relieving cancer-related sleep disturbance. However, research evidence on SAS for managing cancer-related sleep disturbance has not been fully conclusive due to the limited number of existing clinical studies with relatively small sample size and suboptimal methodological quality. Clinical trials with large sample size and robust methodology are warranted in future research

ADAM9 inhibition increases membrane activity of ADAM10 and controls α-secretase processing of amyloid precursor protein

Prodomains of A disintegrin and metalloproteinase (ADAM) metallopeptidases can act as highly specific intra- and intermolecular inhibitors of ADAM catalytic activity. The mouse ADAM9 prodomain (proA9; amino acids 24–204), expressed and characterized from Escherichia coli, is a competitive inhibitor of human ADAM9 catalytic/disintegrin domain with an overall inhibition constant of 280 ± 34 nm and high specificity toward ADAM9. In SY5Y neuroblastoma cells overexpressing amyloid precursor protein, proA9 treatment reduces the amount of endogenous ADAM10 enzyme in the medium while increasing membrane-bound ADAM10, as shown both by Western and activity assays with selective fluorescent peptide substrates using proteolytic activity matrix analysis. An increase in membrane-bound ADAM10 generates higher levels of soluble amyloid precursor protein α in the medium, whereas soluble amyloid precursor protein β levels are decreased, demonstrating that inhibition of ADAM9 increases α-secretase activity on the cell membrane. Quantification of physiological ADAM10 substrates by a proteomic approach revealed that substrates, such as epidermal growth factor (EGF), HER2, osteoactivin, and CD40-ligand, are increased in the medium of BT474 breast tumor cells that were incubated with proA9, demonstrating that the regulation of ADAM10 by ADAM9 applies for many ADAM10 substrates. Taken together, our results demonstrate that ADAM10 activity is regulated by inhibition of ADAM9, and this regulation may be used to control shedding of amyloid precursor protein by enhancing α-secretase activity, a key regulatory step in the etiology of Alzheimer disease.National Institutes of Health (U.S.) (Grant R01EB010246)National Institutes of Health (U.S.) (Grant R01GM081336)Heptagon Fund (London, England)Cancer Research UKWhitehead FoundationDuke University. School of Medicine (Bridge Funding Program)Germany. Bundesministerium für Bildung und ForschungChina (National Fellowship from the Chinese Scholarship Council)Florida State Universit

Evidence for factors associated with diet and physical activity in African and Caribbean countries.

OBJECTIVE: To identify and describe summarized evidence on factors associated with diet and physical activity in low- and middle-income countries in Africa and the Caribbean by performing a scoping review of reviews. METHODS: We searched the Medline®, LILACS, Scopus, Global Health and Web of Science databases for reviews of factors associated with diet or physical activity published between 1998 and 2019. At least 25% of studies in reviews had to come from African or Caribbean countries. Factors were categorized using Dahlgren and Whitehead's social model of health. There was no quality appraisal. FINDINGS: We identified 25 reviews: 13 on diet, four on physical activity and eight on both. Eighteen articles were quantitative systematic reviews. In 12 reviews, 25-50% of studies were from Africa or the Caribbean. Only three included evidence from the Caribbean. Together, the 25 reviews included primary evidence published between 1926 and 2018. Little of the summarized evidence concerned associations between international health or political factors and diet or associations between any factor and physical activity across all categories of the social model of health. CONCLUSION: The scoping review found a wide range of factors reported to be associated with diet and physical activity in Africa and the Caribbean, but summarized evidence that could help inform policies encouraging behaviours linked to healthy diets and physical activity in these regions were lacking. Further reviews are needed to inform policy where the evidence exists, and to establish whether additional primary research is needed

Gastric Malignancy Survival in Zambia, Southern Africa: A two year follow up study

Background: Gastric cancer poses a significant global health burden. It is the second most common cause of cancer death worldwide and the ninth leading cause of cancer mortality in Zambia, at a rate of 3.8/100,000; comparable to USA (2/100,000) and UK (3.4/100,000). Survival data on gastric malignancy in Zambia is not known.Objectives: To provide preliminary survival rates of patients with histologically proven gastric adenocarcinoma in Zambia.Study Design: Using our prospective gastric cancer research database, we conducted a retrospective audit of patients diagnosed with gastric cancer at the University Teaching Hospital, Zambia, from June 2010 until January 2012. We contacted patients or their relatives using phone numbers provided at time of enrollment.Main Outcomes: We reviewed age, sex, demographic data (income, education), body mass index, symptoms, duration of symptoms, treatment (surgery, chemotherapy, radiotherapy or combination) and survival outcome.  Analysis was performed using Kaplan-Meier models and log rank test.Results: Fifty one patients were diagnosed with gastric adenocarcinoma during the study period, but follow-up data were available for 50. Median survival was 142 days. Age, sex, income, education, BMI, tumor location, and treatment modality were not significantly associated with overall survival. In Cox regression models, covariates associated with survival were a history of regular alcohol intake (HR 0.49, 95%CI 0.26,0.92; P=0.025) and intestinal type cancer histology (HR 0.40, 95%CI 0.19,0.83; P=0.01).Conclusion: Prognosis of newly diagnosed gastric cancer in Zambia is poor with significant mortality within 1 yearof diagnosis, particularly among patients with weight loss and dysphagia

Aspects of alcohol use disorder affecting social cognition as assessed using the Mini Social and Emotional Assessment (mini-SEA)

Background Alcohol Use Disorder (AUD) is associated with problems with processing complex social scenarios. Little is known about the relationship between distinct AUD-related factors (e.g., years of problematic drinking), aspects of cognitive function and dysfunction in individuals diagnosed with AUD, and the relative impact these may have on social cognition. Aims To explore differences in social cognition between a group of participants diagnosed with AUD and controls, using a clinical measure, the Mini Social and Emotional Assessment (mini-SEA). The mini-SEA was used to evaluate social and emotional understanding through a facial emotional recognition task and by utilising a series of social scenes some of which contain a faux pas (social error). Methods Eighty-five participants (individuals with AUD and controls) completed demographic questions and a general cognitive and social cognitive test battery over three consecutive days. Results Between group analyses revealed that the participants with AUD performed less well on the faux pas test, and differences were also revealed in the emotional facial recognition task. Years of problematic alcohol consumption was the strongest predictor of poor ToM reasoning. Conclusion These results suggest a strong link between AUD chronicity and social cognition, though the direction of this relationship needs further elucidation. This may be of clinical relevance to abstinence and relapse management, as basic social cognition skills and ability to maintain interpersonal relationships are likely to be crucial to recovery