Search results for: dementia

Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Vivek Kumar

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The effects of physical activity on the human body have been well understood. It just not only keeps us healthy and away from many diseases but also helpful in delay ageing. Those who exercise every day are physically as well as mentally strong. As the age advance, we often see that there is a loss of memory in the elderly people and their retention power weaken with time. The association between physical health and mental health of elderly people nowadays is an important topic of research. Many people at their old age who all were suffering from Alzheimer or Parkinson disease or were at the stage of dementia have been benefited significantly on exercise at daily basis. We would conduct a randomized control trial, where we will select a number of old age people (65 years old or above). These selected old age people will have some sorts of mental illness and currently receiving treatment for the same. We will divide them into 3 groups. The first group of people will receive their normal treatment i.e. taking medicines. The second group of people will receive medicine as well as will do exercise for 45 minutes every day in the early morning, the 3rd group of people will do exercise everyday for 45 minutes but will be given placebo instead of medicine. All the member of these groups will be monitored carefully for 6 months of time and making this sure that all the members of the group are taking medicines or doing exercise according to the group they belong to. The mental status of all the participants will be measured; the data will be analyzed accordingly. Expected results- This research will be helpful in establishing the effect of exercise on the mental health of the old age people. Also, it will be examined that whether the medicines along with regular exercise for can months can cure the mental illness significantly.

Keywords: mental health, elderly people, physical activity, randomized control trial

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Authors: Su-Lin Yu

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This paper will explore how gender and care discourse are intersected, reformulated and contested in American daughters’ caregiving memoirs. In particular, it will attempt to show how gender structure has worked to regulate a daughter’s response to her mother’s illness. In other words, how do certain cultural notions and class difference affect the ways in which the daughter enacts her caregiving response to her mother’s illness? What is the interrelation of female subjectivity and care practice? To understand care and gender politics in the memoirs, this paper will engage in close readings of five texts: Sandra Bullock Simith’s Trading Places: Becoming My Mother’s Mother: A Daughter’s Memoir (2015),Martha Stettinius’s Inside the Dementia Epidemic: A Daughter’s Memoir (2012), Patricia Thompson Collamer’s Grace on the Ledge: a Caregiver's Memoir, Judith Henry’s The Dutiful Daughter's Guide to Caregiving: A Practical Memoir (2015), and The Daughter's Dilemma: A Survival Guide to Caring for an Aging, Abusive Parent by Emily Wanderer Cohen (2018). By analyzing these texts, this paper will show why adult daughters become the primary caregivers, how gender norms and care practices influence a daughter’s thoughts and actions, and how it affects her self-understanding. Taken as a whole, then, the paper will provide an important examination not only of care and gender politics, but also a contribution to the intersecting discourses of illness, death, and mother-daughter relationship.

Keywords: care ethics, daughter-mother relationship, gender politics, memoirs

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Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

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Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

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Authors: L. Paulino Ferreira, M. Gomes Neto, M. Duarte, S. Serra

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Objectives: COVID-19 pandemic has caused older adults to experience a degree of social isolation and loneliness that is unprecedented. Our aim is to review state of the art regarding the consequences of social isolation due to COVID-19 in elderly people. Methods: The authors conducted a search on Medscape and PubMed with the keywords mentioned below, and the most relevant articles were selected. Results: Social isolation leads many elderlies to experience loneliness, anxiety, depression, alcohol abuse, and feelings of abandonment with a perception of being a burden on society. Thus, social isolation has increased the risk for suicide in older people. It is also noteworthy that the exacerbation of psychiatric disorders (such as depression, anxiety, and post-traumatic stress disorder) without correct treatment and follow-up also increases suicide risk. Loneliness is also associated with accelerated cognitive deterioration and dementia. Besides that, during social isolation, it could be more difficult for older people to get medication as well as proper health care. It is also noticed an increase in the risk of falls, poor nutrition, and lack of exercise. All this contributes to weakening elderlies’ immune systems leading to a higher risk of developing infections, cardiovascular events, and cancer, increasing hospitalization and morbimortality. Conclusion: Social isolation in the elderly has a significant impact on physical and mental health, as well as morbimortality and hospitalizations due to non-COVID causes. Nevertheless, further studies will be needed to assess the real dimension of the effects of social isolation due to COVID-19.

Keywords: social isolation, COVID-19, elderly, mental health

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Authors: Jun Hong Lee

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Background: Alzheimer`s disease (AD) I: creases with age and is characterized by the premature progressive loss of neuronal cell. In contrast, cancer cells have inappropriate cell proliferation and resistance to cell death. Objective: We evaluated the association between cancer and AD and also examined the specific types of cancer. Patients and Methods/Material and Methods: This retrospective, nationwide, longitudinal study used National Health Insurance Service – Senior cohort (NHIS-Senior) 2002-2013, which was released by the KNHIS in 2016, comprising 550,000 random subjects who were selected from over than 60. The study included a cohort of 4,408 patients who were first diagnoses as AD between 2003 and 2005. To match each dementia patient, 19,150 subjects were selected from the database by Propensity Score Matching. Results: We enrolled 4,790 patients for analysis in this cohort and the prevalence of AD was higher in female (19.29%) than in male (17.71%). A higher prevalence of AD was observed in the 70-84 year age group and in the higher income status group. A total of 540 cancers occurred within the observation interval. Overall cancer was less frequent in those with AD (12.25%) than in the control (18.46%), with HR 0.704 (95% Confidence Intervals (CIs)=0.0.64-0.775, p-Value < 0.0001). Conclusion: Our data showed a decreased incidence of overall cancers in patients with AD similar to previous studies. Patients with AD had a significantly decreased risk of colon & rectum, lung and stomach cancer. This finding lower than but consistent with Western countries. We need further investigation of genetic evidence linking AD to cancer.

Keywords: Alzheimer, cancer, nationwide, longitudinal study

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Authors: Arrate Barrenechea Garro

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Background: Bilingualism has been shown to enhance cognitive reserve and potentially delay the onset of dementia symptoms. This study investigates the impact of bilingualism on cognitive reserve and the age of diagnosis in Parkinson's Disease (PD). Methodology: The study involves 16 non-demented monolingual PD patients and 12 non-demented bilingual PD patients, matched for age, sex, and years of education. All participants are native Spanish speakers, with Spanish as their first language (L1). Cognitive performance is assessed through a neuropsychological examination covering all cognitive domains. Cognitive reserve is measured using the Cognitive Reserve Index Questionnaire (CRIq), while language proficiency is evaluated using the Bilingual Language Profile (BLP). The age at diagnosis is recorded for both monolingual and bilingual patients. Results: Bilingual PD patients demonstrate higher scores on the CRIq compared to monolingual PD patients, with significant differences between the groups. Furthermore, there is a positive correlation between cognitive reserve (CRIq) and the utilization of the second language (L2) as indicated by the BLP. Bilingual PD patients are diagnosed, on average, three years later than monolingual PD patients. Conclusion: Bilingual PD patients exhibit higher levels of cognitive reserve compared to monolingual PD patients, as indicated by the CRIq scores. The utilization of the second language (L2) is positively correlated with cognitive reserve. Bilingual PD patients are diagnosed with PD, on average, three years later than monolingual PD patients. These findings suggest that bilingualism may contribute to cognitive reserve and potentially delay the onset of clinical symptoms associated with PD. This study adds to the existing literature supporting the relationship between bilingualism and cognitive reserve. Further research in this area could provide valuable insights into the potential protective effects of bilingualism in neurodegenerative disorders.

Keywords: bilingualis, cogntiive reserve, diagnosis, parkinson's disease

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Authors: Jiayan Gou, Kexin He, Xin Zhang, Fei Wang, Liuni Zou

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Background: Homocysteine is a high-risk factor for cognitive decline, and folic acid supplementation can lower homocysteine levels. However, current clinical research results are inconsistent, and the effects of folic acid on homocysteine levels and cognitive function in older people are inconsistent. Objective: The objective of this study is to systematically evaluate the effects of folic acid alone or in combination with other nutrients on homocysteine levels and cognitive function in older adults. Methods: Systematic searches were conducted in five databases, including PubMed, Embase, the Cochrane Library, Web of Science, and CINAHL, from inception to June 1, 2023. Randomized controlled trials were included investigating the effects of folic acid alone or in combination with other nutrients on cognitive function in older people. Results: 17 articles were included, with six focusing on the effects of folic acid alone and 11 examining folic acid in combination with other nutrients. The study included 3,100 individuals aged 60 to 83.2 years, with a relatively equal gender distribution (approximately 51.82% male). Conclusion: Folic acid alone or combined with other nutrients can effectively lower homocysteine level and improve cognitive function in patients with mild cognitive impairment. But for patients with Alzheimer's disease and dementia, the intervention only can reduce the homocysteine level, but the improvement in cognitive function is not significant. In healthy older people, high baseline homocysteine levels (>11.3 μmol/L) and good ω-3 fatty acid status (>590 μmol/L) can enhance the improvement effect of folic acid on cognitive function. This trial has been registered on PROSPERO as CRD42023433096.

Keywords: B-complex vitamins, cognitive function, folic acid, homocysteine

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Authors: Nagda Ibrahim Mady, Shimaa Mohamed Atiha

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In light of actual needs of elderly people and the changes that accompany age in eyesight, hearing, dexterity, mobility, and memory which make aged people unable to carry out the simplest living affairs especially clothing demands. These needs are almost neglected in the current clothing market obligate aged peoples to wear the available choices without any consideration to their actual desires and needs. Fashion designer has gained many experiences that can gather between ergonomics and stages of fashion designing process. Fashion designer can determine the actual needs of aged people and reply these needs with designs that can achieve Improvement to the life quality of aged people besides maintaining good appearance. Thus Fashion designer can help elderly people to avoid negative impacts age leaves on them, either it is psychological or kinetic or that of dementia. Ergonomics in clothing is considered the tools and mechanisms that are used to fit aged people satisfactions supporting them to improve their living using the least time and effort. Providing the elderly with comfort besides maintaining good appearance that can make self–confidence besides independence. From this point of view the research is looking forward to improve the life of aged people through addressing functional clothes that can make elderly independent in the wearing process. Providing in these designs comfort, quality, and practicality and economic cost. Suggesting the suitable fabrics and materials and applying it to the designs to help the elderly perform their daily living customs. Reaching the successful designs that can be acceptable to specialists and to consumers whom they confirm: it supplies their clothing needs and provides the atheistic and functional performance and therefore it gives them better life.

Keywords: ergonomic, design garments, elderly people, life quality

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Authors: Mounia El Jaouhari, Mira Goral, Samir Diouny

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Introduction: Previous research has indicated that language impairments are recognized as a feature of many neurodegenerative disorders, including non-language-led dementia subtypes such as Alzheimer´s disease (AD). In this preliminary study, the focal aim is to quantify the semantic content of naming and connected speech samples of Moroccan patients diagnosed with AD using two tasks taken from the culturally adapted and validated Moroccan version of the Boston Diagnostic Aphasia Examination. Methods: Five individuals with AD and five neurologically healthy individuals matched for age, gender, and education will participate in the study. Participants with AD will be diagnosed on the basis of the Moroccan version of the Diagnostic and Statistial Manual of Mental Disorders (DSM-4) screening test, the Moroccan version of the Mini Mental State Examination (MMSE) test scores, and neuroimaging analyses. The participants will engage in two tasks taken from the MDAE-SF: 1) Picture description and 2) Naming. Expected findings: Consistent with previous studies conducted on English speaking AD patients, we expect to find significant word production and retrieval impairments in AD patients in all measures. Moreover, we expect to find category fluency impairments that further endorse semantic breakdown accounts. In sum, not only will the findings of the current study shed more light on the locus of word retrieval impairments noted in AD, but also reflect the nature of Arabic morphology. In addition, the error patterns are expected to be similar to those found in previous AD studies in other languages.

Keywords: alzheimer's disease, anomia, connected speech, semantic impairments, moroccan arabic

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Authors: Ammar Alobaidy, Lamees Alsawafi, Malak Almawali, Balqees Alabri, Hajer Alhamrashdi

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Background: There is scarce data in the literature concerning the use of Arabic version neuron psychological cognitive tests in the geriatric age group of the Omani population. Objectives: Our aim is to obtain norms for normal elderly Omanis assessed by The Consortium to Establish a Registry for Alzheimer's disease (CERAD) neuro psychological battery and to compare these norms with other studies in the literature. Methods: 84 attendants and visitors of in-patients at Sultan Qaboos University Hospital, elder than 55 years, were interviewed. All participants were assessed by Dementia Rating Scale & Geriatric Depression Scale to ensure the integrity of their activities of daily living and the absence of depression, respectively. The performance of all participants in the CERAD battery was rated by a single rater to optimize the inter-rater reliability. Results: The cut-point for average performance in CERAD battery is dependent on the age, sex, and level of education and cannot be set as a single cut-point for all elderly Omanis. Conclusion: This study has shown the effect of age, sex, and level of education on the cognitive performance of normal elderly Omanis. The normative data obtained from this study can be utilized to differentiate between the cognitive decline of normal aging and the cognitive impairment due to various neuro cognitive disorders in the elderly Omanis, and probably culturally similar Arabic speaking communities.

Keywords: CERAD, neuropsychological battery, normal aging, elderly Omanis

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Authors: Christine Maleesha Withanachchi, Eithne Heffernan, Derek Hoare

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Background: Social isolation (SI} is a major consequence of hearing loss (HL}. Isolation can lead to serious health problems (e.g., dementia and depression). Hearing Aids (HA) is the primary intervention for HL. However, these are less effective in social situations. Interventions are needed for SI in adults with hearing loss (AHL). Objectives: Investigated the relationship between HL and SI. Explored the views of AHL and hearing healthcare professionals (HHP) towards interventions for isolation. Methods: Individual and group semi-structured interviews were conducted. Interviews were conducted at the Nottingham Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Six AHL and seven HHP were recruited via maximum variation sampling. The interview transcripts were analyzed using inductive thematic analysis. Results: Social impacts of HL: Most participants described that HL hurt them. This was in the form of social withdrawal, strain on relationships, and identity loss. Downstream effects of HL: Most audiologists acknowledged that isolation from HL could lead to depression. HL can also lead to exhaustion and unemployment. Impact of stigma: There are negative connotations around HL and HA (e.g. old age) and there is difficulty talking about isolation. The complexity of SI: There can be difficulty separating SI due to HL from SI due to other contributing factors (e.g. comorbidities). Potential intervention for isolation: Participants were unfamiliar with interventions for isolation and few, if any, were targeted for AHL specifically. Most participants thought an intervention should be patient-centered and run by an AHL in the community. Opinions differed regarding whether it should hear specific or generic. Implementation of intervention: Challenges to the implementation of an intervention for SI exist due to the sensitivity of the subject. Conclusions: This study demonstrated that SI is a major consequence of HL and uncovered novel findings related to its interventions. Uptake of interventions offered to AHL to reduce loneliness and social isolation is expected to be better if led by AHL in the community as opposed to HHP led interventions in the hospital or clinic settings.

Keywords: adults with hearing loss, hearing aids, interventions, social isolation

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Authors: Madeline Gibson

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Night shift workers make up an essential part of the modern workforce. However, night shift workers have higher incidences of late in life diseases and earlier mortality. Night shift workers are exposed to constant light and experience circadian rhythm disruption. Sleep disruption is thought to increase oxidative stress, defined as an imbalance of excess pro-oxidative factors and reactive oxygen species over anti-oxidative activity. Oxidative stress can damage cells, proteins and DNA and can eventually lead to varied chronic diseases such as cancer, diabetes, cardiovascular disease, Alzheimer’s and dementia. This review aimed to understand whether night shift workers were at greater risk of oxidative stress and to contribute to a consensus on this relationship. Twelve studies published in 2001-2019 examining 2,081 workers were included in the review. Studies compared both the impact of working a single shift and in comparisons between those who regularly work night shifts and only day shifts. All studies had evidence to support this relationship across a range of oxidative stress indicators, including increased DNA damage, reduced DNA repair capacity, increased lipid peroxidation, higher levels of reactive oxygen species, and to a lesser extent, a reduction in antioxidant defense. This research supports the theory that melatonin and the sleep-wake cycle mediate the relationship between shift work and oxidative stress. It is concluded that night shift work increases the risk for oxidative stress and, therefore, future disease. Recommendations are made to promote the long-term health of shift workers considering these findings.

Keywords: night shift work, coxidative stress, circadian rhythm, melatonin, disease, circadian rhythm disruption

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Authors: Hui-Chi Huang, Su-Ju Yang, Ching-Wei Lin, Jui-Yao Tsai, Liang-Yiang

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Background: Evidence exists that pneumonia is a frequently encountered complication after stroke which is associated with a higher rate of mortality and increased long-term disability Purpose: To determine the predictors associated with the risk of one-year disability in acute stroke. Methods: Data for this longitudinal follow-up study were extracted from a tertiary referral medical center’s stroke registry database in Northern Taipei. Eligible patients with acute stroke admitted to the hospital and completed a one-year follow up were recruited for analysis. Favorable outcome was defined as a modified Rankin Scale score ≤ 2. SAS version 9.2 was used for the multivariable regression analyses to examine the factors correlated with the one-year disability in stroke patients. Results: From January 2012 to December 2013, a total of 1373 (mean age: 70.49±15.4 years, 913(66.5%) males) consecutively administered acute stroke patients were recruited. Overall, the rate of one-year disability was 37.20%(404/1086) in those without post-stroke pneumonia. It increased to 82.93 %(238/287) in patients developed post-stroke pneumonia. Factors associated with increased risk of disability were age ≧ 75(OR= 4.845, p<.0001), female /gender (OR=1.568, p =.0062), previous stroke (OR= 1.868, p = <. 0001) ,dementia (OR= 2.872, p =.0047), ventilator use (OR= 4.653, p <. 0001),age ≧ 75 /pneumonia (OR=1.236, p <. 0001) , ICU admission (OR=3.314, p <.0001) , nasogastric tube insertion (OR= 4.28, p <.0001), speech therapy (OR= 1.79, p =.0142), urinary tract infection (OR= 1.865, p =.0018), estimated glomerular filtration rate (eGFR > 60 )(OR= 0.525, p= .0029), Admission NIHSS >11 (OR= 2.101, p = .0099), Length of hospitalization > 30(d) (OR= 5.182, p <.0001). Conclusion: Older age, severe neurological deficit, complications, rehabilitation intervention, length of hospitalization >30(d), and cognitive impairment were significantly associated with Post-stroke functional impairment, especially those with post-stroke pneumonia. These findings could open new avenues in the management of stroke patients.

Keywords: stroke, risk, pneumonia, disability

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Authors: Mohammad Aladwan

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Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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Authors: David Polcari, Samuel C. Perry, Loredano Pollegioni, Matthias Geissler, Janine Mauzeroll

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ᴅ-serine acts as an endogenous co-agonist for N-methyl-ᴅ-aspartate receptors in neuronal synapses. This makes it a key component in the development and function of a healthy brain, especially given its role in several neurodegenerative diseases such as Alzheimer’s disease and dementia. Despite such clear research motivations, the primary site and mechanism of ᴅ-serine release is still currently unclear. For this reason, we are developing a biosensor for the detection of ᴅ-serine utilizing a microelectrode in combination with a ᴅ-amino acid oxidase enzyme, which produces stoichiometric quantities of hydrogen peroxide in response to ᴅ-serine. For the fabrication of a biosensor with good selectivity, we use a permselective poly(meta-phenylenediamine) film to ensure only the target molecule is reacted, according to the size exclusion principle. In this work, we investigated the effect of the electrodeposition conditions used on the biosensor’s response time and selectivity. Careful optimization of the fabrication process allowed for enhanced biosensor response time. This allowed for the real time sensing of ᴅ-serine in a bulk solution, and also provided in means to map the efflux of ᴅ-serine in real time. This was done using scanning electrochemical microscopy (SECM) with the optimized biosensor to measure localized release of ᴅ-serine from an agar filled glass capillary sealed in an epoxy puck, which acted as a model system. The SECM area scan simultaneously provided information regarding the rate of ᴅ-serine flux from the model substrate, as well as the size of the substrate itself. This SECM methodology, which provides high spatial and temporal resolution, could be useful to investigate the primary site and mechanism of ᴅ-serine release in other biological samples.

Keywords: ᴅ-serine, enzymatic biosensor, microelectrode, scanning electrochemical microscopy

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Authors: J. DeBoard, R. Dietrich, J. Hughes, K. Yurko, G. Harms

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Alzheimer’s disease (AD) is a predominant type of dementia and is likely a major cause of neural network impairment. The pathogenesis of this neurodegenerative disorder has yet to be fully elucidated. There are currently no known cures for the disease, and the best hope is to be able to detect it early enough to impede its progress. Beyond age and genetics, another prevalent risk factor for AD might be traumatic brain injury (TBI), which has similar neurodegenerative hallmarks. Our research focuses on obtaining information and methods to be able to predict when neurodegenerative effects might occur at a clinical level by observation of events at a cellular and molecular level in model mice. First, we wish to introduce our evidence that brain damage can be observed via brain imaging prior to the noticeable loss of neuromuscular control in model mice of AD. We then show our evidence that some blood biomarkers might be able to be early predictors of AD in the same model mice. Thus, we were interested to see if we might be able to predict which mice might show long-term neurodegenerative effects due to differing degrees of TBI and what level of TBI causes further damage and earlier death to the AD model mice. Upon application of TBIs via an apparatus to effectively induce extremely mild to mild TBIs, wild-type (WT) mice and AD mouse models were tested for cognition, neuromuscular control, olfactory ability, blood biomarkers, and brain imaging. Experiments are currently still in process, and more results are therefore forthcoming. Preliminary data suggest that neuromotor control diminishes as well as olfactory function for both AD and WT mice after the administration of five consecutive mild TBIs. Also, seizure activity increases significantly for both AD and WT after the administration of the five TBI treatment. If future data supports these findings, important implications about the effect of TBI on those at risk for AD might be possible.

Keywords: Alzheimer's disease, blood biomarker, neurodegeneration, neuromuscular control, olfaction, traumatic brain injury

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: Ghazal Mortazavi, S. M. J. Mortazavi

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Electricians, power line engineers and power station workers, welders, aluminum reduction workers, MRI operators and railway workers are occupationally exposed to different levels of electromagnetic fields. Mercury is among the most toxic metals. Dental amalgam fillings cause significant exposure to elemental mercury vapour in the general population. Today, substantial evidence indicates that mercury even at low doses may lead to toxicity. Increased release of mercury from dental amalgam fillings after exposure to MRI or microwave radiation emitted by mobile phones has been previously shown by our team. Moreover, our recent studies on the effects of stronger magnetic fields entirely confirmed our previous findings. From the other point of view, we have also shown that papers which reported no increased release of mercury after MRI, may have some methodological flaws. Over the past several years, our lab has focused on the health effects of exposure of laboratory animals and humans to different sources of electromagnetic fields such as mobile phones and their base stations, mobile phone jammers, laptop computers, radars, dentistry cavitrons, and MRI. As a strong association between exposure to electromagnetic fields and mercury level has been found in our studies, our findings lead us to this conclusion that occupational exposure to electromagnetic fields in workers with dental amalgam fillings can lead to elevated levels of mercury. Studies which reported that exposure to mercury can be a risk factor of Alzheimer’s disease (AD) due to the accumulation of amyloid beta protein (Aβ) in the brain and those reported that long-term occupational exposure to high levels of electromagnetic fields can increase the risk of Alzheimer's disease and dementia in male workers support our concept and confirm the significant role of the occupational exposure to electromagnetic fields in increasing the mercury level in workers with amalgam fillings.

Keywords: occupational exposure, electromagnetic fields, workers, mercury release, dental amalgam, restorative dentistry

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Authors: Joan Esper Kuhnly, Jess Holden, Lynn Shelley, Nicole Kuhnly

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Empathy serves as a foundational nursing principle inherent in the nurse’s ability to form those relationships from which to care for patients. Evidence supports, including empathy in nursing and healthcare education, but there is limited data on what methods are effective to do so. Building evidence supports experiential and interactive learning methods to be effective for students to gain insight and perspective from a personalized experience. The purpose of this project is to evaluate learning activities designed to promote the attainment of empathic behaviors across 5 levels of the nursing curriculum. Quantitative analysis will be conducted on data from pre and post-learning activities using the Toronto Empathy Questionnaire. The main hypothesis, that simulation learning activities will increase empathy, will be examined using a repeated measures Analysis of Variance (ANOVA) on Pre and Post Toronto Empathy Questionnaire scores for three simulation activities (Stroke, Poverty, Dementia). Pearson product-moment correlations will be conducted to examine the relationships between continuous demographic variables, such as age, credits earned, and years practicing, with the dependent variable of interest, Post Test Toronto Empathy Scores. Krippendorff’s method of content analysis will be conducted to identify the quantitative incidence of empathic responses. The researchers will use Colaizzi’s descriptive phenomenological method to describe the students’ simulation experience and understand its impact on caring and empathy behaviors employing bracketing to maintain objectivity. The results will be presented, answering multiple research questions. The discussion will be relevant to results and educational pedagogy in the nursing curriculum as they relate to the attainment of empathic behaviors.

Keywords: curriculum, empathy, nursing, simulation

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Authors: Elissar Mansour, Emily Chen, Tracee Fernandez, Mariam Basheti, Christopher Gordon, Bandana Saini

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Sleep is an essential process for the maintenance of several neurobiological processes such as memory consolidation, mood, and metabolic processes. It is known that sleep patterns vary with age and is affected by multiple factors. While non-pharmacological strategies are generally considered first-line, sedatives are excessively used in the older population. This study aimed to explore the management of sleep in residential aged care facilities (RACFs) by nurse professionals and to identify the key factors that impact provision of optimal sleep health care. An inductive thematic qualitative research method was employed to analyse the data collected from semi-structured interviews with registered nurses working in RACF. Seventeen interviews were conducted, and the data yielded three themes: 1) the nurses’ observations and knowledge of sleep health, 2) the strategies employed in RACF for the management of sleep disturbances, 3) the organizational barriers to evidence-based sleep health management. Nurse participants reported the use of both non-pharmacological and pharmacological interventions. Sedatives were commonly prescribed due to their fast action and accessibility despite the guidelines indicating their use in later stages. Although benzodiazepines are known for their many side effects, such as drowsiness and oversedation, temazepam was the most commonly administered drug. Sleep in RACF was affected by several factors such as aging and comorbidities (e.g., dementia, pain, anxiety). However, the were also many modifiable factors that negatively impacted sleep management in RACF. These include staffing ratios, nursing duties, medication side effects, and lack of training and involvement of allied health professionals. This study highlighted the importance of involving a multidisciplinary team and the urge to develop guidelines and training programs for healthcare professionals to improve sleep health management in RACF.

Keywords: registered nurses, residential aged care facilities, sedative use, sleep

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Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

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Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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Authors: Ali Bayram, Remzi Yiğiter

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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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Authors: Sakshi Chopra, Harsimarpreet Kaur, Ashima Nehra

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Objectives: Malingering is fabricating or exaggerating the symptoms of mental or physical disorders for a variety of secondary gains or motives, which may include financial compensation; avoiding work; getting lighter criminal sentences; or simply to attract attention or sympathy. Malingering is different from somatization disorder and factitious disorder. The prevalence of malingering is unknown and difficult to determine. In an estimated study in forensic population, it can reach up to 17% cases. But the accuracy of such estimates is questionable as successful malingerers are not detected and thus, not included. Methods: The case study of a 58 years old, right handed, graduate, pre-morbidly working in a national company with reported history of stroke leading to head injury; cerebral infarction/facial palsy and dementia. He was referred for disability certification so that his job position can be transferred to his son as he could not work anymore. A series of Neuropsychological tests were administered. Results: With a mental age of < 2.5 years; social adaptive functioning was overall < 20 showing profound Mental Retardation, less than 1 year social age in abilities of self-help, eating, dressing, locomotion, occupation, communication, self-direction, and socialization; severely impaired verbal and performance ability, 96% impairment in Activities of Daily Living, with an indication of very severe depression. With inconsistent and fluctuating medical findings and problem descriptions to different health professionals forming the board for his disability, it was concluded that this patient was malingering. Conclusions: Even though it can be easily defined, malingering can be very challenging to diagnosis. Cases of malingering impose a substantial economic burden on the health care system and false attribution of malingering imposes a substantial burden of suffering on a significant proportion of the patient population. Timely, tactful diagnosis and management can help ease this patient burden on the healthcare system. Malingering can be detected by only trained mental health professionals in the clinical setting.

Keywords: disability, India, malingering, neuropsychological assessment

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Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

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Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

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Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

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Authors: Hannele Laaksonen, Seija Nyqvist, Kari Nurmes

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Objectives: In the year 2011 the City of Vaasa started to develop know-how in the technology and the introduction of services for aging people in cooperation with the Polytechnic Novia University of Applied Sciences and VAMK, University of Applied Sciences. The project´s targets included: to help elderly people to maintain their ability to function, to provide them social and physical activities, to prevent their social exclusion, to decrease their feelings of loneliness and insecurity and to develop their technical know-how. Methods: The project was built based on open source code, tailor-made service system and user interface for the elderly living at home and their families, based on the users´ expectations and experiences of services. Activation-TV®-project vas carried out 1.4.2011-31.3.2014. A pilot group of eight elderly persons, who were living at home, were selected to the project. All necessary technical means as well as guidance and teaching equipment were provided to the pilot group. The students of University of Applied Sciences (VAMK, Novia) and employees of Center of Ageing were made all programs to the Activation-TV®. The project group were interviewed after and before intervention. The data were evaluated both qualitatively and quantitatively. Results: The built service includes a video library, a group room for interactive programs and a personal room for bilateral meetings and direct shipment. The program is bilingual and produced in both national languages. The Activation TV® reduced elderly peoples´ (n=8) feelings of emptiness, added mental well-being and quality of life with social contacts. Relatives felt, that they were able to get in to older peoples´ everyday life with Activation TV®. Discussion: The built application was tailored to the model that has not been developed elsewhere in Finland. This model can be copied from one server to another and thus transferred to other municipalities but the program requires its own personnel system management and maintenance as well as program production cooperation between the different actors. This service can be used for the elderly who are living at home without dementia.

Keywords: mental well-being, quality of life, elderly people, Finland

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: Vichayada Laohapiboolkul

Abstract:

Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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