A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimers disease

Background Presenilin-1 (PSEN1) is one of the causative genes for early onset Alzheimers disease (EOAD). Recently, emerging studies reported several novel PSEN1 mutations among Asian. We describe a male with EOAD had a pathogenic PSEN1 mutation. Case presentation A 53-year-old male presented with memory decline, followed by difficulty in finding ways. Patient had positive family history, since his mother and one of his brother was also affected with dementia. Brain magnetic resonance imaging (MRI) scan showed mild degree of atrophy of bilateral hippocampus and parietal lobe. 18F-Florbetaben-PET (FBB-PET) revealed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and precuneus. Whole exome analysis revealed a heterozygous, probably pathogenic PSEN1 (c.695G > T, p.W165C) mutation. Interestingly, Trp165Cys mutation is located in trans membrane (TM)-III region, which is conserved between PSEN1/PSEN2. In vitro studies revealed that PSEN1 Trp165Cys could result in disturbances in amyloid metabolism. This prediction was confirmed by structure predictions and previous in vitro studies that the p.Trp165Cys could result in decreased Aβ42/Aβ40 ratios. Conclusion We report a case of EOAD having a pathogenic PSEN1 (Trp165Cys) confirmed with in silico and in vitro predictions.This work was supported by a National Research Foundation of Korea (NRF) Grants, awarded by the Korean government (MEST, No. 2017R1A2B4012636 & 2017R1C1B5017807). Dr. An SS receives the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST, No. 2017R1A2B4012636). Dr. Eva Bagyinszky receives the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST, No. 2017R1C1B5017807). Dr. Giau VV reports no disclosure. Dr. Pyun JM reports no disclosure. Dr. Suh J reports no disclosure. Dr. Kim SY reports no disclosure

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

From An Idea to A Start-up: Barriers and Solutions for Undergraduates as Potential Entrepreneurs in Vaasa

The purpose of this thesis was to explore barriers and seek for solution as starting small venture in Vaasa. As the trend of establishing a business in Vaasa among students is becoming more and more popular. However, lacking know-how knowledge causes difficulties or barriers in forming their own idea and a real business. In order to solve this short-coming, benchmarking is suggested. Case study was adopted as research strategy, a document and semi-structure interview with Stefan Jungar and Nga Nguyen as two students creating their own venture; and Margi Niemelä, a university lecturer in entrepreneur topic. Documentary method was based on business journals, books and many other reliable online sources. Three semistructured interviews were carried out to increase the realis-tism of research finding about business practices. The samples were chosen through purposive sampling. The results in analysis section indicate barriers as well as solutions. Barriers are mainly related to knowledge, language and culture, entry to the market. Being an entrepreneur requires know-how knowledge, hard work, devotion, determination and passion. Solutions are suggested: segmenting the market to increase competi-tiveness, evaluating the idea carefully to lower the risks, learning a country culture and language by joining in its local community groups and gaining experience in the field before creating one’s venture.Yhä useammat oppilaat suosivat ajatusta yrityksen perustamisesta Vaasaan. Tiedon puute aiheuttaa kuitenkin usein ongelmia oman ihanteellisen yrityksen perustamisessa. Tämän ongelman ratkaisemiseksi olisi suositeltavaa käyttää benchmarking-menetelmää, yritysten toimintatapojen oppimiseksi. Tämän työn tavoite on kartoittaa esteet yrityksen perustamisessa Vaasassa, ja etsiä niihin ratkaisuja. Tutkimus-strategiana käytetään tapaustutkimusta ja Stefan Jungarin ja Nga Nguyenin haastatteluja heidän omien liikeyritystensä perustamisesta, sekä Margit Niemelän, koulun yrittäjyys luennoitsijan haastattelua. Tapaustutkimuksessa käytetään yritysten kirjanpitodokumentteja, kirjoja ja monia muita luotettavia lähteitä. Tutkimuksessa suoritettiin kolme avointa haastattelua yritysten toimintatapojen selville saamiseksi. Näytteet valittiin määrätietoisella näytteenotolla. Analyysissä ilmenevä lopputulos osoittaa sekä esteitä, että ratkaisuja. Esteet liittyvät pääasiassa tiedon puutteeseen, kieleen, kulttuuriin ja alkuun pääsyyn. Yrittäjänä oleminen vaatii tietotaitoa, kovaa työtä, kunnianhimoa, sisua, omistautumista ja monia muita asioita. Ehdotettuja ratkaisuja ovat markkinoiden segmentointi kilpailukyvyn parantamiseksi, liikeidean tarkka arviointi riskien vähentämiseksi, kulttuurin ja kielen oppiminen liittymällä paikallisiin tapahtumiin ja kokemuksen hankkiminen alalta ennen oman yrityksen perustamista

Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen

The vast majority of patients with Alzheimer&#8217;s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with &#946;-amyloid (1-42) (A&#946;), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition has been discovered in the brains of AD patients and mouse models. In this study, biochemical approaches and the epitope mapping immunoassay were employed to characterize binding epitopes within the Fbg and complementary epitopes in A&#946;. We discovered the A&#946;5&#8315;25 peptide as the most critical region for the interaction, which can be inhibited by specific monoclonal and polyclonal antibodies against the central region of A&#946;. A&#946; binding to Fbg may block plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of plasmin-resistant fibrin degradation fragments. Our study elucidates the A&#946;&#8315;Fbg interaction that may involve the mechanism by which A&#946;&#8315;Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person&rsquo;s age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer&rsquo;s disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of A&beta;40, A&beta;42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

In the two years since the SARS-CoV-2 pandemic started, it has caused over 5 million deaths and 400 million infected cases, and the world continues to be on high alert for COVID-19. Among the variants of interest and concern of SARS-CoV-2, the current Omicron (B.1.1.529) and stealth Omicron (BA.2) raised serious concerns due to rapid rates of infection caused by numerous mutations in the spike protein, which could escape from the antibody-mediated neutralization and increase the risk of reinfections. Hence, this work aims to describe the most relevant mutations in the SARS-CoV-2 spike protein, discuss vaccine against variant of concerns, describe rare adverse events after COVID-19 vaccination, introduce the most available promising COVID-19 vaccine candidates, and provide few perspectives of the future variants

Optimization of Mulberry Extract Foam-Mat Drying Process Parameters

Mulberry powder was created from the extract using a foam-mat drying process. The studies aimed to evaluate the effects of egg albumin, carboxymethyl cellulose (CMC), digestion-resistant maltodextrin (DRM) contents, and whipping time (5 to 15 min) on the foam properties. The impact of different drying temperatures (60 to 75 &deg;C) on the quality of the finished mulberry powder was also noted. The best foam expansion/stability value was determined using multiple regression models as a function of egg albumin, CMC, DRM, and whipping time. The results indicated that the main influencing factors for the foam properties were whipping time followed by egg albumin, CMC, and DRM. Optimum values of foam expansion and stability were achieved at 467.9% and 97.02%, respectively. The foam had a porous structure and good stability for subsequent drying, with optimal contents of egg albumin, CMC, and DRM used at 7.6%, 0.4%, and 2%, respectively, along with a whipping time of 14.5 min. The established models had a high coefficient of determination (R2 &gt; 0.9) and a high correlation between the predicted and observed values. Therefore, the model could be adjusted to determine the characteristics of the foam suitable for subsequent drying. The optimal values were then also verified. Minimal fluctuations (1.78&ndash;2.98%) between the experimental data and the optimal value were found. The drying temperature also significantly affected the quality of the mulberry powder. The foam was dried at 65 &deg;C for 4 h to produce apowder with a beautiful light color (L* = 62.65), a characteristic purple-red color of mulberry (a* = 5.97). The moisture, water activity, and anthocyanin content of the finished mulberry powder were 4.57%, 0.3, and 5.4 mg/g, respectively

Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease

Alzheimer&#8217;s disease (AD), Parkinson&#8217;s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington&#8217;s disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in AD, PD, and FTD/ALS genes could be found in clinical familial and sporadic AD. To further elucidate the missing heritability in early-onset Alzheimer&#8217;s disease (EOAD), we genetically characterized a Thai EOAD cohort by Next-Generation Sequencing (NGS) with a high depth of coverage, capturing variants in 50 previously recognized AD and other related disorders&#8217; genes. A novel mutation, APP p.V604M, and the known causative variant, PSEN1 p.E184G, were found in two of the familiar cases. Remarkably, among 61 missense variants were additionally discovered from 21 genes out of 50 genes, six potential mutations including MAPT P513A, LRRK2 p.R1628P, TREM2 p.L211P, and CSF1R (p.P54Q and pL536V) may be considered to be probably/possibly pathogenic and risk factors for other dementia leading to neuronal degeneration. All allele frequencies of the identified missense mutations were compared to 622 control individuals. Our study provides initial evidence that AD and other neurodegenerative diseases may represent shades of the same disease spectrum, and consideration should be given to offer exactly embracing genetic testing to patients diagnosed with EOAD. Our results need to be further confirmed with a larger cohort from this area

Developing a nutritious soup product using purple sweet potatoes supplemented with composite of vegetables and freezed-dried chicken

Abstract This research aimed to develop a nutritious instant purple sweet potato soup (PSP) combination with a variety of vegetables and freeze-dried chicken. The nutritional characteristics of the product were evaluated. The current study employs principal component analysis (PCA), consumer preference mapping, and check-all-that-apply (CATA) data processing to describe sensory instant mixed soup attributes. The results showed that the soup was made from the formula F2 (PSP flour 47.5%, orange-fleshed sweet potato flour 12.5%, potatoes 6%, banana 7%, mushroom 8%, petit poise 3%, pumpkin 5%, protein powder 5% and cream powder 6%) gave good quality, high sensory value and attractive colors product. The PCA identified important soup attributes such as sweetness, milk flavor, vegetable odor, and color. Adding 15% freeze-dried chicken improved the quality of mixed soup products with energy distribution from macronutrients: proteins 24%, carbohydrates 65%, and lipids 10%. The anthocyanin and β-carotene content analyzed from the product was 13.1 mg/100 g and 370.2 μg/100 g. Score analysis according to the CATA model with two main components accounting for 95.57% of the variance in sensory attribute data, showing liking attributes of mixed soup sample that the panelists preferred in color, flavor, chicken meat distribution, and sweetness. The essential nutritional characteristics of mixed soup have been carefully analyzed