Anemia and dementia among the elderly: the Sao Paulo Ageing & Health Study

Background: Anemia and dementia are common diseases among the elderly, but conflicting data are available regarding an association between these two conditions. We analyzed data from the Sao Paulo Ageing & Health Study to address the relationship between anemia and dementia. Methods: This cross-sectional observational study included participants aged 65 years and older from a deprived area of the borough of Butantan, Sao Paulo, Brazil. Data about demographics, education, income, and cognitive and daily life function were collected, as well as blood samples. Anemia and dementia were defined according to WHO and DSM-IV criteria, respectively. Results: Of the 2267 subjects meeting the inclusion criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total blood count and were included in the analysis. Anemia was diagnosed in 203 (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was higher in patients with dementia according to univariate analysis (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.41, p = 0.01), but this association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76-2.33, p = 0.32). Further multivariate adjustment did not change the results. Conclusion: Although anemia and dementia are frequent disorders in older people, we found their relationship to be mediated exclusively by aging in this low-income population from Sao Paulo.

The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology

Background: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time. Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification. Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.

Opposing Roles for Cannabinoid Receptor Type-1 (CB1) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) on the Modulation of Panic-Like Responses in Rats

The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety-and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. Neuropsychopharmacology (2012) 37, 478-486; doi:10.1038/npp.2011.207; published online 21 September 2011

Delays in the diagnosis of tuberculosis in a town at the triple border of Brazil, Paraguay, and Argentina

Objective. To identify the factors linked to patients and health services in delays in the diagnosis of tuberculosis. Methods. Epidemiological study in Foz do Iguacu, Parana, Brazil, 2009. The Primary Care Assessment Tool, adapted for appraising tuberculosis treatment, was the instrument used. Descriptive statistics techniques were used, such as frequency distributions, central tendency and dispersion measurements (median and interquartile intervals), and odds ratios. Results. There were greater delays in seeking health services for those in the age group 60 years and older, for females, for patients with low levels of education, and for patients with poor knowledge of the disease. Clinical variables (being a new case and HIV infection) and behavioral variables (use of tobacco and alcohol consumption) were not linked with delays in diagnosis. The median time delays before diagnosis attributable to patients and to the health services were 30 days and 10 days, respectively. Emergency 24-hour medical services and primary health care services were not effective in identifying suspicious cases of tuberculosis and requesting tests to confirm the diagnosis, with a high percentage of referrals to the Tuberculosis Control Program clinic. Conclusions. Going to primary health care services for diagnosis increased the time before diagnosis of the disease was reached. The Tuberculosis Control Program clinic was more effective in diagnosis of tuberculosis, due to the training of the staff and to an organized process for receiving patients, including the availability of tests to support the diagnosis.

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. The cytokines present at highest concentrations in the rat NP were TNF-alpha, IL-1 beta and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-alpha, IL-1 beta and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

Spectrum of cognitive impairment in neurocysticercosis Differences according to disease phase

Objectives: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. Methods: Forty treatment-naive patients with C-NC aged 37.6 +/- 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. Results: Patients with C-NC presented 9.4 +/- 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. Conclusions: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages. Neurology (R) 2012; 78: 861-866

Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder

Objective: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naive adults with obsessive-compulsive disorder (OCD). Method: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. Results: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p = 0.008); higher verbal memory on the California Verbal Learning Test (p = 0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p = 0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p = 0.002). Conclusion: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context. (C) 2012 Elsevier Inc. All rights reserved.

Desigualdade social e os estudos epidemiológicos: uma reflexão

Os indicadores sociais se tornaram imprescindíveis no elenco de variáveis dos estudos epidemiológicos a partir da constatação de que a determinação dos agravos à saúde é complexa e multidimensional. Nessa perspectiva, a desigualdade social vem ocupando destaque como um fator explicativo das condições de saúde das populações. O objetivo é discutir as diferentes concepções que norteiam a seleção dos indicadores utilizados nos estudos epidemiológicos e abordar os efeitos psicossociais nos seres humanos acarretados pela desigualdade social. Foi realizada uma revisão da literatura acerca dos estudos epidemiológicos que utilizaram os indicadores de desigualdade social e capital social para uma melhor compreensão dos problemas de saúde, bem como uma investigação no campo da sociologia e da psicologia social. De acordo com a pesquisa pode-se constatar que há controvérsias sobre o efeito da desigualdade social na saúde humana pelo fato desses indicadores serem baseados, majoritariamente, pela renda e capacidade de consumo dos indivíduos. Da mesma forma, os indicadores de capital social em nível cognitivo e estrutural são muito limitados para compreender o dinamismo das relações sociais. Nesse sentido, são necessários mais estudos para a construção de indicadores sociais que contemplem a complexidade das sociedades modernas.

Are mental health problems and depression associated with bruxism in children?

Renner AC, da Silva AAM, Rodriguez JDM, Simoes VMF, Barbieri MA, Bettiol H, Thomaz EBAF, Saraiva MC. Are mental health problems and depression associated with bruxism in children? Community Dent Oral Epidemiol 2011. (C) 2011 John Wiley & Sons A/S Abstract Objectives: Previous studies have found an association between bruxism and emotional and behavioral problems in children, but reported data are inconsistent. The objective of this study was to estimate the prevalence of bruxism, and of its components clenching and grinding, and its associations with mental problems and depression. Methods: Data from two Brazilian birth cohorts were analyzed: one from 869 children in Ribeirao Preto RP (Sao Paulo), a more developed city, and the other from 805 children in Sao Luis SL (Maranhao). Current bruxism evaluated by means of a questionnaire applied to the parents/persons responsible for the children was defined when the habit of tooth clenching during daytime and/or tooth grinding at night still persisted until the time of the assessment. Additionally, the lifetime prevalence of clenching during daytime only and grinding at night only was also evaluated. Mental health problems were investigated using the Strength and Difficulties Questionnaire (SDQ) and depression using the Childrens Depression Inventory (CDI). Analyses were carried out for each city: with the SDQ subscales (emotional symptoms, conduct problems, peer problems, attention/hyperactivity disorder), with the total score (sum of the subscales), and with the CDI. These analyses were performed considering different response variables: bruxism, clenching only, and grinding only. The risks were estimated using a Poisson regression model. Statistical inferences were based on 95% confidence intervals (95% CI). Results: There was a high prevalence of current bruxism: 28.7% in RP and 30.0% in SL. The prevalence of clenching was 20.3% in RP and 18.8% in SL, and grinding was found in 35.7% of the children in RP and 39.1% in SL. Multivariable analysis showed a significant association of bruxism with emotional symptoms and total SDQ score in both cities. When analyzed separately, teeth clenching was associated with emotional symptoms, peer problems, and total SDQ score; grinding was significantly associated with emotional symptoms and total SDQ score in RP and SL. Female sex appeared as a protective factor for bruxism, and for clenching and grinding in RP. Furthermore, maternal employment outside the home and white skin color of children were associated with increased prevalence of teeth clenching in SL. Conclusions: Mental health problems were associated with bruxism, with teeth clenching only and grinding at night only. No association was detected between depression and bruxism, neither clenching nor grinding. But it is necessary to be cautious regarding the inferences from some of our results.

Clinical and sociodemographic factors in a sample of older subjects experiencing depressive symptoms

Objectives This study aims to determine the frequency of clinically significant depressive symptoms (CSDS) in a community sample of older Brazilians and to examine their relationship with sociodemographic factors, cognitive and functional impairment (CFI), and medical illness. Methods A total of 1145 subjects aged 60?years or older living in the City of Ribeirao Preto, State of Sao Paulo, Brazil, were interviewed. The following instruments were used: a 10-item scale for screening of depressive symptoms in older people, the mini mental state examination, the Fuld Object Memory Evaluation, the Informant Questionnaire on Cognitive Decline in the Elderly, the Bayer Activities of Daily Living Scale, and a sociodemographic and clinical questionnaire. Results The frequency of CSDS was 15.7%. Logistic regression analysis indicated that being previously depressed, having CFI, having lower level of education, using psychotropics, and not engaging in physical exercise were related to CSDS. On the other hand, being a woman, older, medically ill, employed, or married was not associated with CSDS. Conclusions Consistent with previous reports, lower education, lack of physical activity, and CFI were significantly associated with higher frequencies of CSDS. Further investigations are necessary to clarify the occurrence of depression and possible modifiable factors in developing countries such as Brazil. Copyright (C) 2011 John Wiley & Sons, Ltd.

Body weight, metabolism and clock genes

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction

Saliva and dental erosion

Dental erosion is a multifactorial condition. The consideration of chemical, biological and behavioral factors is fundamental for its prevention and therapy. Among the biological factors, saliva is one of the most important parameters in the protection against erosive wear. Objective: This review discusses the role of salivary factors on the development of dental erosion. Material and Methods: A search was undertaken on MeDLINe website for papers from 1969 to 2010. The keywords used in the research were "saliva", "acquired pellicle", "salivary flow", "salivary buffering capacity" and "dental erosion". Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. Results: Several characteristics and properties of saliva play an important role in dental erosion. Salivary clearance gradually eliminates the acids through swallowing and saliva presents buffering capacity causing neutralization and buffering of dietary acids. Salivary flow allows dilution of the acids. In addition, saliva is supersaturated with respect to tooth mineral, providing calcium, phosphate and fluoride necessary for remineralization after an erosive challenge. Furthermore, many proteins present in saliva and acquired pellicle play an important role in dental erosion. Conclusions: Saliva is the most important biological factor affecting the progression of dental erosion. Knowledge of its components and properties involved in this protective role can drive the development of preventive measures targeting to enhance its known beneficial effects.