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Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize L-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice.
This work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing L-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ moighlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy.
The present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy.
Technological advances in healthcare have enabled patients to participate in digital self-assessment, with reported benefits of enhanced healthcare efficiency and self-efficacy. This report describes the design and validation of a patient-administered preanaesthesia health assessment digital application for gathering medical history relevant to preanaesthesia assessment. Ro 20-1724 concentration Effective preoperative evaluation allows for timely optimization of medical conditions and reduces case cancellations on day of surgery.
Using an iterative mixed-methods approach of literature review, surveys and panel consensus, the study sought to develop and validate a digitized preanaesthesia health assessment questionnaire in terms of face and criterion validity. A total of 228 patients were enrolled at the preoperative evaluation clinic of a tertiary women's hospital. Inclusion criteria include age ≥ 21 years, scheduled for same-day-admission surgery, literacy in English and willingness to use a digital device. Patient perception oools.
Self-administration of digitized preanaesthesia health assessment is acceptable to patients and reliable in eliciting medical history. Further iteration should focus on improving reliability of the digital tool, adapting it for use in other languages and incorporating clinical decision tools.
Our objective was to find which additional factors can influence the favorable result in stroke patients after receiving fibrinolytic and/or endovascular treatment, quantified as a more than 30% improvement of the NIHSS score at 7 days.
This is a retrospective study to find factors that could influence a favorable evolution of patients with stroke that underwent fibrinolytic and or thrombectomy using the NIHSS score changes. At the admission in the hospital, blood glucose, blood count, coagulation time, INR, aPTT, PT, platelet count, NIHSS questionnaire and ASPECTS score were collected. NIHSS was assessed at the admission, after 1 h, after 2 h, after 24 h and after 7 days.
As compared to the initial evaluation, at 7 days after admission 59% (72) of patients have improved with more than 30% the NIHSS. Higher levels of systolic blood pressure, glycemia and lower ASPECTS score at admission were observed in non-achievers. The value of INR contributed to model for every unit increase of INR, the chance of better outcome decreases by 90,1%. High glycemia has also a negative impact for every unit increase, the chance of better outcome decreases by 24%. Higher initial ASPECTS score is associated with better outcomes each point increase of ASPECTS score at initial evaluation, increases the chance of better outcome by 154.2%.
Males, older age, diabetes, and hyperglycemia correlate with a worse outcome after cerebral stroke regardless of the benefit yielded fibrinolytic and/or thrombectomy therapy. In this study, patients with the above-mentioned factors did not improve more than 30% of baseline NIHSS score from admission to the 7th day.
Males, older age, diabetes, and hyperglycemia correlate with a worse outcome after cerebral stroke regardless of the benefit yielded fibrinolytic and/or thrombectomy therapy. In this study, patients with the above-mentioned factors did not improve more than 30% of baseline NIHSS score from admission to the 7th day.
Apathy is one of the most common symptoms of Alzheimer's disease (AD), however, correlations of apathy with demographic variables, cognitive functions, neuropsychiatric symptoms, activity of daily living and olfactory functions in AD patients are still lacking comprehensive investigations.
This is a cross-sectional study. Total 124 typical AD patients were consecutively recruited from April 2014 to April 2017. In 124 AD patients, 47 cases (37.9%) were male and 77 cases were female; patients' age were 43-93 years with an average of 68 years. Patients were divided into AD with apathy (AD-A) and AD with no apathy (AD-NA) groups according to the score of Modified Apathy Evaluation Scale, then were evaluated cognitive functions, neuropsychiatric symptoms and activity of daily living, and tested olfactory functions. Above variables were compared between AD-A and AD-NA groups. Further correlation analyses and linear regression analysis were performed between apathy and above variables.
Compared with AD-NA groul fluency and instrumental activities of daily living in AD patients might be related to the common brain area involved in their pathogeneses.
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