Association of Vitamin D Levels with Incident All-Cause Dementia in Longitudinal Observational Studies: A Systematic Review and Meta-analysis.

BACKGROUND: The role of vitamin D is not only limited to bone health and pathogenesis of chronic diseases. Evidence now suggests that it is also involved in the development of various dementias and Alzheimer's disease (AD). OBJECTIVE: To carry out a systematic review and meta-analysis to evaluate the association between vitamin D levels and increased risk of incident all-cause dementia in longitudinal studies. DESIGN: We conducted a systematic review and meta-analysis using the electronic bibliographic databases PubMed and Scopus. SETTING: Prospective cohort studies. PARTICIPANTS: Community-dwelling older adults. MEASUREMENTS: Vitamin D serum concentrations were categorized in three groups: normal levels (>50 nmol/L), insufficient levels (25 - 49.9 nmol/L), and deficient levels (<25 nmol/L). We performed a meta-analysis using the general inverse variance method to calculate the pooled risk of AD and all-cause dementia according to vitamin D levels. Random-effects or fixed-effect model were used to calculate the pooled risk based on the heterogeneity analysis. RESULTS: Five studies were included in the meta-analysis. The pooled risk of all-cause dementia and AD was significantly higher in those with deficient serum vitamin D level compared to those with normal level (1.33, CI95% [1.15, 1.54], and 1.87, CI95% [1.03, 3.41], respectively). Those with insufficient level also had a higher pooled risk of all-cause dementia and AD, but the strength of association was less robust (1.14 CI95% [1.02, 1.27] and 1.25, CI95% [1.04 - 1.51], respectively). CONCLUSION: We found a gradient effect for the risk of all-cause dementia and AD according to the vitamin D level, with higher risk in those in the deficient levels group and intermediate risk in those with insufficient levels. Our findings were limited by the relatively small number of studies included in the meta-analysis and their geographic restriction.

Update of dental and maxillofacial alterations in patients with pycnodysostosis / Atualização das alterações dentárias e dos ossos gnáticos em pacientes com picnodisostose

ABSTRACT Pycnodysostosis is a rare, autosomal recessive genetic condition, which causes a decrease in bone remodeling, resulting in different clinical and radiographic manifestations. This case series aims to describe two clinical cases diagnosed at the Department of Oral and Maxillofacial Surgery and Traumatology of a University on the Northeast of Brazil. There are two complex cases involving osteomyelitis and dental and bone alterations of the jaws. It is concluded that the knowledge of oral and maxillofacial characteristics of this syndrome are required to plan appropriate treatment for patient in order to avoid complications of dental treatments due to inadequate bone remodeling.

RESUMEN La picnodisostosis es una enfermedad genética rara autosómica, recesiva, con disminución de la remodelación ósea, que ocasiona varias manifestaciones clínicas y radiográficas. Este estudio describe dos casos clínicos diagnosticados en el servicio de cirugía y traumatología bucomaxilofacial de una universidad en el nordeste de Brasil. Los casos son complejos y envuelven osteomielitis, alteraciones dentales y óseas de las mandíbulas. Es necesario conocer las características orales y maxilofaciales de este síndrome para planear el tratamiento adecuado al paciente, con la intención de evitar complicaciones de tratamientos dentales debido a la remodelación ósea inadecuada.

RESUMO A picnodisostose é uma condição genética rara, autossômica recessiva, que ocasiona diminuição da remodelação óssea, resultando em várias manifestações clínicas e radiográficas. Este estudo pretende descrever dois casos clínicos diagnosticados no Serviço de Cirurgia e Traumatologia Bucomaxilofacial de uma universidade no nordeste do Brasil. São dois casos complexos que envolvem osteomielite e alterações dentárias e ósseas dos maxilares. É necessário o conhecimento das características orais e maxilofaciais dessa síndrome para planejar o tratamento adequado para o paciente, a fim de se evitar complicações de tratamentos dentários em virtude do remodelamento ósseo inadequado.

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways.

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein-protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10(-8) per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.

Água salina e biofertilizante bovino na produção de frutos e alocação de biomassa em noni (Morinda citrifolia L. ) / Saline water and bovine biofertilizer on yield and biomass allocation in noni plants (Morinda citrifolia L. )

RESUMO: Têm sido evidenciado que os compostos orgânicos exercem ação mitigadora dos efeitos tóxicos dos sais às plantas, promovendo maior crescimento e desenvolvimento em solos com excesso de sais. Nessa direção, um experimento foi desenvolvido para avaliar os efeitos do biofertilizante bovino na produção de frutos e alocação de biomassa pelos diversos órgãos de plantas de noni, irrigadas com águas salinas. Os tratamentos foram distribuídos em blocos ao acaso, com quatro repetições e duas plantas por parcela, adotando o arranjo fatorial 5 x 2, correspondente a salinidade das águas de irrigação de 0,5; 1,5; 3,0; 4,5; 6,0 dS m-1, em substratos sem e com biofertilizante bovino, aplicado uma única vez, em volume correspondente a 10% do volume do substrato, um dia antes da instalação do experimento. As variáveis avaliadas foram: salinidade do solo, expressa pela condutividade elétrica do extrato de saturação do solo; número de frutos; massa média de fruto; produção de frutos por planta; e alocação de biomassa pelas raízes, caules, folhas e frutos. O aumento da salinidade da água de irrigação elevou o caráter salino do solo desde "não salino" para "fortemente salino" e, inibiu a produção de frutos e a acumulação de biomassa seca das plantas de noni em geral, mas, com maior intensidade nos tratamentos sem o insumo orgânico. O biofertilizante estimula o crescimento e a produção de plantas de noni cultivadas sob irrigação com águas de alta salinidade.

ABSTRACT: Organic compounds have shown to exercise a mitigating action on salts in plants and they promote growth and development in salt stress environments. In this sense, an experiment was carried out in order to evaluate the effects of saline water irrigation and bovine biofertilizer on yield and biomass allocation by the various organs of noni plants. Treatments were arranged in a randomized block design with four replications and two plants per plot using the 5 x 2 factorial design, which correspond to the salinity levels of irrigation water of 0.5, 1.5, 3.0, 4.5 and 6.0 dS m-1 in substrates with and without bovine biofertilizer, applied to the soil once, in the volume corresponding to 10% of the volume of the substrate one day before the implementation of the experiment. The variables evaluated were soil salinity, expressed as electrical conductivity of the soil saturation extract, fruit number, fruit weight and fruit yield per plant, and biomass allocation by roots, stems, leaves and fruit. The increasing salinity of the water for irrigation increased the saline character of the soil from non-saline to saline soil and inhibited the production and accumulation of dry biomass in noni plants in general but with more intensity in the plants of the treatments without bovine biofertilizer applied to the soil in liquid form. The biofertilizer stimulates the growth and production of noni plants grown under irrigation with high salinity water.

Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression.

Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment. The biological mechanisms underlying cognitive impairment in LLD are complex and likely involve abnormalities in multiple pathways, or 'cascades,' reflected in specific biomarkers. Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD. To this end, we used a data-driven comprehensive proteomic analysis (multiplex immunoassay including 242 proteins), along with measures of structural brain abnormalities (gray matter atrophy and white matter hyperintensity volume via magnetic resonance imaging), and brain amyloid-ß (Aß) deposition (PiB-positron emission tomography). We analyzed data from 80 older adults with remitted major depression (36 with mild cognitive impairment (LLD+MCI) and 44 with normal cognitive (LLD+NC)) function. LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis. Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015). We observed no differences in gray matter volume or brain Aß deposition between groups. Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias). Cognitive impairment in LLD seems to be related to greater cerebrovascular disease along with abnormalities in immune-inflammatory control, cell survival, intracellular signaling, protein and lipid homeostasis, and clotting processes. These results suggest that individuals with LLD and cognitive impairment may be more vulnerable to accelerated brain aging and shed light on possible mediators of their elevated risk for progression to dementia.

Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population.

PURPOSE: Correlate OCT-derived measures of drusen and retinal pigment epithelium (RPE) atrophy areas (RAs) with demographic features in an elderly population. PATIENTS AND METHODS: Subjects aged 50 years and older underwent Cirrus OCT scanning. Drusen area and volume were obtained from the macula within a central circle (CC) of 3 mm and a surrounding perifoveal ring (PR) of 3-5 mm, using the RPE analysis software (6.0). RA measurements were generated for the 6 × 6 mm(2) retinal area. Gender, age, smoking status, and systolic blood pressure (SBP) were considered. RESULTS: A total of 434 eyes were included. RA was larger in women (0.63±0.16 vs 0.26±0.08 mm(2), P=0.05) and with increasing age. The PR drusen area increased with increasing age (P<0.001), whereas the CC drusen area remained stable after the age of 70 years (0.25±0.06 mm(2) for ages 70-79 years and 0.25±0.07 mm(2) for ages >80 years). Drusen volume in the CC was smaller after the age of 80 years (0.009±0.003 mm(3)) compared with the 70- to 79-year-old group (0.02±0.008 mm(3)). Drusen measurements were similar between smokers and nonsmokers, but the PR drusen area (0.29 mm(2), P=0.05) and volume (0.40 mm(3), P=0.005) were correlated with years smoked. RA (0.24 mm(2), P=0.10), PR drusen area (0.29 mm(2), P=0.05), and volume (0.40 mm(3), P=0.005) were found to be directly associated with SBP. There was a high correlation between the eyes of the same subject. CONCLUSION: OCT-based automated algorithms can be used to analyze and describe drusen and geographic atrophy burden in such population-based studies of elderly patients.

Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders.

Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. More recently, based on findings from translational research, lithium has also been regarded as a neuroprotective agent and a candidate drug for disease-modification in certain neurodegenerative disorders, namely, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and, more recently, Parkinson's disease (PD). The putative neuroprotective effects of lithium rely on the fact that it modulates several homeostatic mechanisms involved in neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Such a wide range of intracellular responses may be secondary to two key effects, that is, the inhibition of glycogen synthase kinase-3 beta (GSK-3ß) and inositol monophosphatase (IMP) by lithium. In the present review, we revisit the neurobiological properties of lithium in light of the available evidence of its neurotrophic and neuroprotective properties, and discuss the rationale for its use in the treatment and prevention of neurodegenerative diseases.

Comparison between precipitin and ELISA tests in the bloodmeal detection of Aedes aegypti (Linnaeus) and Aedes fluviatilis (Lutz) mosquitoes experimentally fed on feline, canine and human hosts.

The identification of arthropod bloodmeals is important in many epidemiological studies, as, the understanding of the life cycle of vectors and the pathogens they transmit, as well as helping to define arthropods' control strategies. The precipitin test has been used for decades, but ELISA is slowly becoming more popular. To compare the two tests for sensitivity, specificity and accuracy to detect small insect bloodmeals, Aedes aegypti or Ae. fluviatilis mosquitoes were fed either on feline, canine or human hosts. Mosquitoes were frozen at 6, 12, 24, 48 or 72 h after feeding. Precipitin test showed better specificity and accuracy and ELISA test showed higher sensitivity. Better results with both tests were achieved when mosquitoes were frozen within 48 h from feeding.