Alzheimer´s Disease and Age-related Macular Degeneration could simultaneously be treated or prevented with a single therapeutic intervention

Alzheimer ´s diseases becomes the most common type of dementia in the world. There is more of 5.4 million AD patients in America, more than 6 million patients in China, and 35.6 million patients worldwide. AD and other dementias worldwide will increase to 67.5 million by 2030 and 115.4 million by 2050. In the aging population, two of the most common neurodegenerative diseases, AD and AMD, could simultaneously treated or prevented with single therapeutic intervention

Multiclass Prediction Model for Student Grade Prediction Using Machine Learning

This work was supported in part by the Ministry of Higher Education through the Fundamental Research Scheme under Grant FRGS/1/2018/ICT04/UTM/01/1, in part by the Speci~c Research Project (SPEV) at the Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic, under Grant 2102-2021, in part by the Universiti Teknologi Malaysia (UTM) under Research University Grant Vot-20H04, and in part by the Malaysia Research University Network (MRUN) under Grant Vot 4L876.Today, predictive analytics applications became an urgent desire in higher educational institutions. Predictive analytics used advanced analytics that encompasses machine learning implementation to derive high-quality performance and meaningful information for all education levels. Mostly know that student grade is one of the key performance indicators that can help educators monitor their academic performance. During the past decade, researchers have proposed many variants of machine learning techniques in education domains. However, there are severe challenges in handling imbalanced datasets for enhancing the performance of predicting student grades. Therefore, this paper presents a comprehensive analysis of machine learning techniques to predict the nal student grades in the rst semester courses by improving the performance of predictive accuracy. Two modules will be highlighted in this paper. First, we compare the accuracy performance of six well-known machine learning techniques namely Decision Tree (J48), Support Vector Machine (SVM), Naïve Bayes (NB), K-Nearest Neighbor (kNN), Logistic Regression (LR) and Random Forest (RF) using 1282 real student's course grade dataset. Second, we proposed a multiclass prediction model to reduce the over tting and misclassi cation results caused by imbalanced multi-classi cation based on oversampling Synthetic Minority Oversampling Technique (SMOTE) with two features selection methods. The obtained results showthat the proposed model integrates with RF give signi cant improvement with the highest f-measure of 99.5%. This proposed model indicates the comparable and promising results that can enhance the prediction performance model for imbalanced multi-classi cation for student grade prediction.Science and Technology Development Fund (STDF)Ministry of Higher Education & Scientific Research (MHESR) FRGS/1/2018/ICT04/UTM/01/1Specific Research Project (SPEV) at the Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic 2102-2021Universiti Teknologi Malaysia (UTM) Vot-20H04Malaysia Research University Network (MRUN) 4L87

Association between calcium intake, parathormone levels and blood pressure during pregnancy*

SUMMARY Purpose: To evaluate the association between calcium intake from diet, calciotropic hormones (PTH, PTH-rp), vasoactive regulators (endothelin, nitric oxide) and blood pressure levels during pregnancy, birth and puerperium. Method: In a prospective study 149 healthy normotensive primigravidas were followed-up from 15 weeks of gestation to puerperium. Daily calcium intake, calciuria, PTH, PTH-rp, endothelin, nitrite-nitrate, and Holter Test were assessed. Linear regression models were performed to evaluate the association between calcium intake, blood pressure levels and the laboratory tests. Multivariate regression models were performed to control potential confounders. Results: A significant increase of calcium intake during pregnancy was observed (931±301 mg/day to 1,195±467 mg/day, p<0.001). Plasma PTH-rp, endothelin, and nitrite-nitrate levels did not change during pregnancy. Among the women 38 (25.4%) had low calcium intake (<800 mg/day) with a larger increase of systolic and diastolic blood pressure during pregnancy (p=0.04) birth (p=0.006) and puerperium (p=0.01). After adjusting for other factors the multivariate analyses showed statistical association between low calcium intake, high parathormone levels and high systolic blood pressure levels during pregnancy (p=0.002). Conclusion: Low calcium intake during pregnancy is associated with a larger increase of systolic blood pressure and high parathormone levels. Keywords: Calcium intake; Endothelin; PTH: PTH-rp: Preeclampsia; Nitric oxide. Asociación entre consumo de calcio, niveles de parathormona y presión arterial en el embarazo RESUMEN Objetivo: Evaluar la asociación entre la ingesta de calcio en el embarazo, los niveles de presión arterial, las hormonas calciotrópicas (PTH, PTH-rp) y sustancias vasorreguladoras (endotelina, óxido nítrico). Métodos: Se realizó un estudio prospectivo con 149 primigrávidas normotensas que fueron incluidas en la semana 15 de gestación con seguimiento y evaluación hasta el puerperio. Se evaluó la ingesta diaria de calcio, la monitoría Holter de 24 horas, la calciuria, PTH, PTH-rp, la endotelina, nitritos y nitratos. Se siguieron modelos de regresión lineal para evaluar la asociación entre la ingesta de calcio, la presión arterial, las hormonas calciotrópicas y los vasorreguladores. Para controlar las variable

Appropriate medication prescribing in elderly patients: how knowledgeable are primary care physicians? A survey study in Parma, Italy.

What is known and Objective:  Increasing attention is being paid to inappropriate medication prescribing for the elderly. A growing body of studies have detected a prevalence of inappropriate prescribing ranging from 12% to 40% worldwide, including Regione Emilia-Romagna, Italy. To improve quality of prescribing, a multi-phase pilot project in the Local Health Unit (LHU) of Parma, Regione Emilia-Romagna, was established. This phase aimed to assess primary care physicians\u27 knowledge of appropriate prescribing in elderly patients. Methods:  In total, 155 primary care physicians (51% of the total), convened by the LHU of Parma for an educational session, were asked to complete anonymously a 19-item paper survey. Knowledge of inappropriate medication use in the elderly was assessed using seven clinical vignettes based on the 2002 Beers Criteria. Topics tested included hypertension, osteoarthritis, arrhythmias, insomnia and depression. Data regarding physician\u27s perceived barriers to appropriate prescribing for elderly patients were also collected. To evaluate the relationship between physician knowledge scores and physician characteristics, physicians were classified as having a \u27low score\u27 (three or below) or a \u27high score\u27 (six or more) with respect to their knowledge of prescribing for the elderly. Results and Discussion:  All physicians completed the survey. Most physicians (88%) felt confident in their ability to prescribe appropriate medications for the elderly. Thirty-nine physicians (25%) received a \u27high score\u27 compared to 26 (17%) who received a \u27low score\u27. \u27Lower score\u27 respondents had been in practice for a longer time (P \u3c 0·05) than \u27higher score\u27 respondents. Perceived barriers to appropriate prescribing included potential drug interactions (79% of respondents) and the large number of medications a patient is already taking (75%). What is new and Conclusion:  The study results show an unsatisfactory knowledge of appropriate prescribing among primary care physicians in the LHU of Parma, especially among older physicians. Educational strategies tailored to primary care physicians should be establish to enhance knowledge in this area and improve quality of prescribing

Interés terapéutico de las estatinas en el tratamiento de la aterosclerosis

Los inhibidores de la HMG-Co A reductasa o estatinas, son fármacos muy utilizados en el tratamiento de lahipercolesterolemia, ya que consiguen disminuir la concentración plamática de lipoproteína de baja densidad (LDL)regulando la síntesis endógena de colesterol y por tanto, de receptores para LDL.Recientemente se ha comprobado como el tratamiento prolongado con estos fármacos disminuyen la mortalidad ymorbilidad cardiovascular. Este fenómeno puede explicarse por los efectos beneficiosos directos de las estatinas enel desarrollo de la placa de ateroma. Las estatinas disminuyen la proliferación y migración de células de musculaturalisa vascular e inducen apoptosis de estas células. También previenen la oxidación de LDL y la formación de célulasespumosas, reducen la respuesta inflamatoria asociada a la aterosclerosis, normalizan los fenómenos de coagulacióny fibrinolisis y por último mejoran significativamente la función endotelial. Todas estas propiedades parecen estarmediadas compuestos isoprenoides intermediarios de la ruta metabólica de la HMG-Co A reductasa, y son independientesde la concentración de colesterol en el medio.Por tanto, las estatinas también podrían ser utilizadas en enfermedades asociadas a disfunción endotelial independientementede las cifras analíticas de LDL, tal y como sucede en la hipertensión

Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community