Structural and functional changes related to memory deficit in non-demential elderly individuals

Objetivo: Verificar as alterações estruturais e funcionais, evidenciadas através da imagem por ressonância magnética, relacionadas aos déficits de memória identificados em idosos normais, quando comparados a adultos jovens. Metodologia: Procedeu-se à revisão sistemática, cujo protocolo obedeceu ao fluxograma do Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Foram investigadas as bases de dados PubMed, Scopus, EBSCO, utilizando o gerenciador de referências JabRef, na versão 2.10, e o Web of Science, pelo website. Foram incluídos artigos de estudos quase experimentais, transversais, em coorte ou tipo caso-controle, publicados entre 2005 e 2014, em periódicos indexados nacionais e internacionais, cuja amostra incluísse idosos a partir de 60 anos, não dementes, submetidos à investigação de alterações estruturais e funcionais do sistema nervoso central, por ressonância magnética e sua associação com déficits de memória avaliados por testes neuropsicológicos. Resultados: Quanto à técnica de imagem empregada, identificaram-se dois estudos com imagem por ressonância magnética estrutural, seis estudos com utilização de imagem por ressonância magnética funcional, e quatro estudos que empregaram ambas as técnicas. Nos 12 estudos foi identificado o emprego de 38 testes neuropsicológicos distintos, com uma média de cinco testes por estudo, com variação de um a 12 testes. Dentre os testes mais usados, estiveram o WAIS Digit Span Backwards (em sete estudos), o Trail Making Test A and B (em quatro estudos) e o Wechsler Memory Scale (em quatro estudos). Conclusão: Os estudos demonstraram que no envelhecimento normal, ocorre redução do volume de substância branca para-hipocampal, do volume do hipocampo e do córtex entorrinal com redução de memória verbal, possivelmente por desmielinização das fibras; redução das vias que ligam o lobo temporal e frontal, contribuindo para a redução da memória episódica, da memória de trabalho e da fluência verbal; redução da supressão de informações irrelevantes, o que contribui para menor registro de informação; alterações das áreas frontal e parietal que comprometem a memória de reconhecimento; modificações na atividade e na conectividade do default mode network; reorganização das funções cognitivas, bem como alentecimento de resposta por provável redução de ativação do córtex pré- frontalObjective: Based on Magnetic Resonance Imaging (MRI), verify the structural and functional changes related to memory deficits in non-demented elderly individuals in comparison with young adults. Methodology: Proceeded a systematic review based on Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) fluxogram. The search was done on PubMed, Scopus and EBSCO databases using JabRef 2.10, and Web of Science. It was included in the analysis quasi-experimental, cross-sectional, cohort and case-control studies published between 2005 and 2014 in national and international indexed periodicals that had as sample: non-demented individuals older than 60 years old, who were submitted to MRI investigation of their for any brain structural and functional changes associated with memory deficits, identified in neuropsychologicals tests. Results: About the imaging technique, we reviewed studies that used structural MRIs (two articles), functional MRIs (six articles), both techniques (four articles). In the 12 studies, 38 distinct neuropsychological tests were used, an average of five different tests for each study (variation of 1-12). The most used tests were WAIS Digit Span Backwards (seven articles), Trail Making Test A and B (four articles) and Wechsler Memory Scale (four articles). Conclusion: The review showed that in normal aging the parahippocampal white substance, the hippocampus volume and entorhinal cortex slightly shrink, causing verbal memory reduction, possibly due to fiber demyelination; reduced connections between temporal and frontal lobes contributing to an impairement of episodic, working memory and verbal fluency; reduction suppression of irrelevant information, affecting the register of information; changes on frontal and parietal areas, compromising recognition memory; modifications in activity and connectivity of the default mode network; reorganization of cognitive functions and also a slower response, probably due to reduction of pre-frontal cortex activatio

The Prevalence and Correlation of Non-motor Symptoms in Adult Patients with Idiopathic Focal or Segmental Dystonia

Background: Idiopathic focal dystonia is a motor syndrome associated with dysfunction of basal ganglia circuits. Observations have suggested that many other non-motor symptoms may also be part of the clinical picture. The aim was to assess the prevalence and correlation of non-motor symptoms in patients with common idiopathic focal or segmental dystonia. Methods: In a single-center cross-sectional case–control study, we evaluated the presence of pain, neuropsychiatric symptoms, and sleep alterations in 28 patients with blepharospasm, 28 patients with cervical dystonia, 24 patients with writer’s cramp, and 80 control subjects matched for sex, age, and schooling. We obtained clinical and demographic data, and evaluated patients using the Fahn–Marsden Dystonia Rating Scale and other specific scales for dystonia. All subjects completed the following questionnaires: Beck Depression Inventory, Beck Anxiety Inventory, Social Phobia Inventory, Apathy Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Brief Pain Scale, and the World Health Organization Quality of Life brief scale. Results: The patients presented more symptoms of depression, anxiety, and apathy than the control subjects. They also reported worse quality of sleep and more pain complaints. Patients with blepharospasm were the most symptomatic subgroup. The patients had worse quality of life, and the presence of pain and symptoms of apathy and depression were the main influences for these findings, but not the severity of motor symptoms. Discussion: Patients with dystonia, especially those with blepharospasm, showed higher prevalence of symptoms of depression, anxiety, apathy, worse quality of sleep, and pain. These symptoms had a negative impact on their quality of life

Multiprofessional care of patients with diabetes mellitus at the endocrinology outpatient clinic of the university hospital of the Ribeirão Preto school of medicine (HCFMRP-USP)

The present study describes the flow of care delivery and activities with patients carriers of diabetes mellitus by a health multiprofessional team from the Endocrinology Outpatient Clinic of the University Hospital of the Ribeirão Preto School of Medicine. This program, according to the proposal of the America’s Declaration about Diabetes, aims at assuring to diabetes carriers conditions to acquire knowledge and skills regarding self-care.O presente estudo descreve o fluxo de atendimento e as atividades desenvolvidas pela equipe multiprofissional de saúde do Ambulatório de Endocrinologia e Metabologia do HCFMRPUSP, junto aos pacientes com diabetes mellitus. Este programa, em consonância aos propósitos da Declaração das Américas sobre Diabetes, visa assegurar que os pacientes com diabetes estejam em condições de adquirir conhecimentos e aptidões para o autocuidado

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Many-Body Dynamics of Dipolar Molecules in an Optical Lattice

We use Ramsey spectroscopy to experimentally probe the quantum dynamics of disordered dipolar-interacting ultracold molecules in a partially filled optical lattice, and we compare the results to theory. We report the capability to control the dipolar interaction strength. We find excellent agreement between our measurements of the spin dynamics and theoretical calculations with no fitting parameters, including the dynamics’ dependence on molecule number and on the dipolar interaction strength. This agreement verifies the microscopic model expected to govern the dynamics of dipolar molecules, even in this strongly correlated beyond-mean-field regime, and represents the first step towards using this system to explore many-body dynamics in regimes that are inaccessible to current theoretical techniques.Physic

Iodine Atoms: A New Molecular Feature for the Design of Potent Transthyretin Fibrillogenesis Inhibitors

The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis

FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas

Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) in the same samples. The frequency of FasL detection was 30–40% in T and was 60–100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms. © 1999 Cancer Research Campaig

Potential plasma markers of type 1 and type 2 leprosy reactions: a preliminary report

<p>Abstract</p> <p>Background</p> <p>The clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil.</p> <p>Methods</p> <p>A nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), interleukin (IL)- IL12p70, IL2, IL17, IL1 β, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1α), 1 beta (MIP1β), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Rα and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF).</p> <p>Results</p> <p>Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.</p> <p>Conclusion</p> <p>Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.</p