Pharmacogenetic Analyses of Therapeutic Effects of Lipophilic Statins on Cognitive and Functional Changes in Alzheimer's Disease.

Background: Pharmacogenetic effects of statins on clinical changes in Alzheimer's disease (AD) could be mediated by epistatic interactions among relevant genetic variants involved in cholesterol metabolism.

Objective: To investigate associations of HMGCR (rs3846662), NR1H2 (rs2695121), or CETP (rs5882&rs708272) with cognitive and functional changes in AD, with stratification according to APOEɛ4 carrier status and lipid-lowering treatment with lipophilic statins.

Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and global ratings, with prospective neurotranslational associations documented for one year.

APOE ε4 Carrier Status as Mediator of Effects of Psychotropic Drugs on Clinical Changes in Patients With Alzheimer's Disease.

Objective: Neuropsychiatric syndromes have been associated with memory dysfunction and risk of and earlier onset of dementia, but how psychotropic drugs affect clinical changes in Alzheimer's disease is not entirely clear. This study aimed to assess the prospective effects of psychotropic drugs on cognitive and functional changes in Alzheimer's disease according to APOE ε4 carrier status.

Methods: The study included consecutive outpatients with late-onset Alzheimer's disease (N=193) and examined score variations at 1 year on the following tests: Clinical Dementia Rating sum of boxes, Mini-Mental State Examination, Severe Mini-Mental State Examination (SMMSE), Brazilian version of the Zarit Caregiver Burden Interview, Index of Independence in Activities of Daily Living, and Lawton's Instrumental Activities of Daily Living Scale.

Selected LDLR and APOE Polymorphisms Affect Cognitive and Functional Response to Lipophilic Statins in Alzheimer's Disease.

Effects of statins over clinical changes in Alzheimer's disease (AD) are usually non-significant, but epistatic interactions between genetic variants involved in cholesterol metabolism could be important for such effects. We aimed to investigate whether LDLR single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also considering APOE haplotypes and lipid-lowering treatment with lipophilic statins for stratification. Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and caregiver burden, with prospective neurotranslational correlations documented for 1 year.

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis.

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N  = 130; N  = 81) and 567 age-matched controls (N  = 317; N  = 250).

Analysis of 8q24.21 miRNA cluster expression and copy number variation in gastric cancer.

 To analyze gene expression and copy number of five miRNAs (, , , and ) localized in this chromosome region in gastric cancer (GC).  65 paired neoplastic and non-neoplastic specimens collected from GC patients and 20 non-neoplastic gastric tissues from cancer-free individuals were included in this study. The expression levels of the five miRNAs were accessed by real time qPCR and were correlated.

Lifetime Risk Factors for Functional and Cognitive Outcomes in Patients with Alzheimer's Disease.

Lifetime risk factors for cognitive and functional decline in Alzheimer's disease (AD) are not fully understood, and were prospectively evaluated in patients with low mean schooling from São Paulo, Brazil. Consecutive outpatients with late-onset AD were assessed for APOE haplotypes and the following potential baseline predictors: gender, schooling, age at dementia onset, lifetime urban living and sanitary conditions, occupational complexity, cognitive and physical activities, cerebrovascular risk factors (obesity, lifetime alcohol use and smoking, length of arterial hypertension, diabetes mellitus, and a dyslipidemic profile), use of a pacemaker, creatinine clearance, body mass index, waist circumference, head traumas with unconsciousness, treated systemic bacterial infections, amount of surgical procedures under general anesthesia, and family history of AD. Participants were followed from October 2010 to May 2017 for baseline risk factor associations with time since dementia onset for Clinical Dementia Rating and Mini-Mental State Examination score changes.

Longitudinal lipid profile variations and clinical change in Alzheimer's disease dementia.

Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.

Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia.

Objective:: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage.

Methods:: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121.

Results:: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior.

MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

Background: Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response.

Material And Methods: We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer.

YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE role in the tumor development and metastasis process.

We previously observed reduced YWHAE (14-3-3ε) protein expression in a small set of gastric cancer samples. YWHAE may act as a negative regulator of the cyclin CDC25B, which is a transcriptional target of MYC oncogene. The understanding of YWHAE role and its targets is important for the better knowledge of gastric carcinogenesis.

BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer.

Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay.

Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer.

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer.

The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study.

Objectives: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated.

Methods: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy.

Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease.

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy.

Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report.

Differential expression of extracellular matrix genes in glenohumeral capsule of shoulder instability patients.

Anterior shoulder instability is a common orthopedic problem. After a traumatic shoulder dislocation, patients present a plastic deformation of the capsule. The shoulder instability biology remains poorly understood.

Comprehensive selection of reference genes for expression studies in meniscus injury using quantitative real-time PCR.

The meniscus plays critical roles in the knee function. Meniscal tears can lead to knee osteoarthritis. Gene expression analysis may be a useful tool for understanding meniscus tears, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies.

Risk factors for cognitive and functional change in one year in patients with Alzheimer's disease dementia from São Paulo, Brazil.

Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimer's disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores.