CAMCOG as a screening tool for diagnosis of Mild Cognitive Impairment and Dementia in a Brazilian clinical sample of moderate to high education

Background The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. Methods One hundred and fifty-seven older adults (mean age: 69.6 +/- 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 +/- 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. Results The cut-off values were: 92/93 for dementia is controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. Conclusions The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer`s disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation

We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.

High prevalence of pituitary magnetic resonance abnormalities and gene mutations in a cohort of Brazilian children with growth hormone deficiency and response to treatment

Data were retrospectively collected from 69 Brazilian patients (45 boys) with growth hormone deficiency (GHD) who received exogenous growth hormone (GH) for a median duration of 4 years (range 1-13 years). Forty-two patients had multiple pituitary hormone deficiencies and 27 had isolated GHD. Peak GH was <7 ng/ml (IRMA) or <3.2 ng/ml (IFMA) after two stimulation tests.. Therapy was started at median age of 10.0 years (range 2.2-21.6 years), bone age of 5.8 years (0.5-13.5 years) and height standard deviation score -4.4 (range -9.3 to -1.6). MRI revealed pituitary abnormalities in 87% of patients. Homozygous mutations in PROP-1, GHRH-R, GH-1 or HESX-1 genes were found in 12 patients. Mean height velocities were 3.3 pretreatment and 10.3, 7.8, 7.4 and 6.4 cm/yr, respectively, during 1-4 years of treatment with GH. In conclusion, the high prevalence (96%) of genetic and/or pituitary abnormalities probably reflects the stringent diagnostic criteria used, and GH replacement resulted in significant catch-up growth.

High prevalence of dementia among older adults from poor socioeconomic backgrounds in Sao Paulo, Brazil

Background: The aim of this study was to determine the prevalence of dementia in a socioeconomically disadvantaged population of older adults living in the city of Sao Paulo, Brazil. Methods: A cross-sectional one-phase population-based study was carried out among all residents aged >= 65 in defined census sectors of an economically disadvantaged area of Sao Paulo. Identification of cases of dementia followed the protocol developed by the 10/66 Dementia Research Group. Results: Of 2072 individuals in the study, 105 met the criteria for a diagnosis of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for both men and women after age 75 years, but was stable from 65 to 74 years. Low education and income were associated with increased risk of dementia. Conclusions: The prevalence of dementia among older adults from low socioeconomic backgrounds is high. This may be partly due to adverse socioeconomic conditions and consequent failure to compress morbidity into the latter stages of life. The increasing survival of poorer older adults with dementia living in developing countries may lead to a rapid increase in the prevalence of dementia worldwide.

High numbers of human skin cancers express MMP2 and several integrin genes

Background: Basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and cutaneous malignant melanoma (MM) are solid skin cancers derived from different cell types, with different ability to metastasize. Several subtypes of integrins and matrix metalloproteinases (MMP) have been related to malignization and metastasis processes. This work aimed at a quantitative evaluation of skin cancers expressing eight integrins and MMP2 genes. Methods: Expression of integrins and MMP2 genes was evaluated on fresh tumor biopsies from BCC, SCC and MM, and respective controls, by the reverse transcriptase polychain reaction (RT-PCR) technique. Results: More than 90% tumors expressed alpha 6a, beta 1, beta 3 and beta 6 (non-melanoma), and alpha 5a, alpha 6a and MMP2 (MM). Up to 100% controls also expressed beta 1 and beta 3. The results were significant for alpha 6a in BCC (p = 0.026), alpha 6b in SCC (p = 0.035), alpha 2a in BCC (p = 0.003), beta 5 and beta 6 in BCC (p = 0.005). MMP2 was expressed in 100% MM (p = 0.0004). Conclusion: Integrin subunits alpha 2a and alpha 6a would be interesting targets for BCC anti-tumor therapy, as well as alpha 6b in case of SCC. The elevated number of BCC expressing alpha 2 and alpha 6, and of MM expressing alpha v and MMP2, corroborate literature data.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Immediate and lasting improvements in weight distribution seen in baropodometry following a high-velocity, low-amplitude thrust manipulation of the sacroiliac joint

The biomechanics of the sacroiliac joint makes the pelvic segment responsible for proper weight distribution between lower extremities; however, it is known to be susceptible to altered mobility. The objective of this study was to analyze baropodometric responses following thrust manipulation on subjects with sacroiliac joint restrictions. Twenty asymptomatic subjects were submitted to computerized baropodometric analysis before, after, and seven days following sacroiliac manipulation. The variables peak pressure and contact area were obtained at each of these periods as the average of absolute values of the difference between the right and left foot based on three trials. Data revealed significant reduction only in peak pressure immediately after manipulation and at follow-up when compared to pre-manipulative values (p < 0.05). Strong correlation was found between the dominant foot and the foot with greater contact area (r - 0.978), as well as between the side of joint restriction and the foot with greater contact area (r = 0.884). Weak correlation was observed between the dominant foot and the foot with greater peak pressure (r = 0.501), as well as between the side of joint restriction and the foot with greater peak pressure (r = 0.694). The results suggest that sacroiliac joint manipulation can influence peak pressure distribution between feet, but contact area does not seem to be related to the biomechanical aspects addressed in this study. (C) 2011 Elsevier Ltd. All rights reserved.

High voltage electrical stimulation as an alternative treatment for chronic ulcers of the lower limbs

High voltage electrical stimulation has been recommended as a means of accelerating the wound healing process. The effects of high voltage electrical stimulation were evaluated in the treatment of three volunteers with chronic ulcers of the lower limbs. After fifteen weeks of treatment, a reduction was found in the area of all the ulcers, suggesting that high voltage electric stimulation is an effective therapeutic option for chronic ulcers.

High and Low Frequency TENS Reduce Postoperative Pain Intensity After Laparoscopic Tubal Ligation A Randomized Controlled Trial

Background: Transcutaneous electrical nerve stimulation (TENS) is an effective adjunctive therapy for postoperative pain; however, effects of different frequencies Of stimulation have not been systematically investigated. Laparoscopic sterilization (LS) causes significant pain in the early postoperative period and requires substantial postoperative medication. Therefore, we studied the effects of TENS on postoperative pain after LS through placement of Yoon fallopian rings in a prospective, randomized, double-blinded, and placebo-controlled study. Methods: Sixty-four patients undergoing LS for uterine tube ligation were randomly allocated to receive either active TENS or placebo TENS. Postoperative pain was evaluated using a standard I I-point numeric rating scale and the McGill Pain Questionnaire (MPQ)-pain rating index and number of words chosen. Both high frequency (100 Hz) and low frequency (4 Hz) TENS, at strong, but comfortable sensory intensity, were applied for 20 minutes through 4 electrodes placed around the surgical incision immediately after Surgery. Pain was assessed before and after application of TENS when patients were at postanesthesia care unit (PACU). Results: Both high and low frequency TENS significantly decreased postoperative pain intensity when compared with before administration of TENS using the numeric rating scale (P = 0.001), pain rating index (P = 0.001), and number of words chosen (P 0.001) compared with placebo TENS (P = 0.001). TENS in combination with standard pharmacologic analgesic treatment was efficacious for postoperative pain relief after LS. Conclusions: We recommend regular use of multimodal therapy with TENS and analgesic drugs after LS with placement of Yoon rings.

A low-protein, high-carbohydrate diet increases the adipose lipid content without increasing the glycerol-3-phosphate or fatty acid content in growing rats

Le taux de triacylglycerol (TAG) qui s`accumule dans le tissu adipeux depend de 2 mecanismes opposes : la lipogenese et la lipolyse. Nous avons montre anterieurement que le poids des lipides du tissu adipeux de l`epididyme (EPI) de meme que leur taux augmentent chez les rats en croissance soumis a une diete hypoproteique hyperglucidique (HPHG) pendant 15 jours. La presente etude a eu pour but d`examiner les voies impliquees dans la lipogenese et la lipolyse qui regulent l`accumulation des lipides dans le tissu. On a evalue in vivo la synthese de novo des acides gras, qui s`est revelee similaire chez les rats soumis a la diete HPHG ou a une diete temoin; toutefois, chez les rats soumis a la diete HPHG, une diminution de l`activite de la lipoproteine lipase dans le tissus adipeux de l`EPI a ete observee, ce qui laisse croire a une diminution de la capture des acides gras des lipoproteines circulantes. La diete HPHG n`a eu aucun effet sur la synthese du glycerol-3-phosphate (G3P) par la glycolyse ou la glyceroneogenese. L`activite de la glycerokinase, c.-a-d. la phosphorylation du glycerol issu de l`hydrolyse du TAG endogene pour former le GP3, n`a pas ete modifiee non plus par la diete HPHG. A l`oppose, les adipocytes des rats HPHG stimules par la norepinephrine ont eu une plus faible reponse lipolytique, meme si le taux lipolytique basal des adipocytes a ete similaire chez les 2 groupes. Ainsi, les resultats donnent a penser que la diminution de l`activite lipolytique stimulee par la norepinephrine joue un role essentiel dans l`augmentation du TAG observee dans le tissu adipeux de l`EPI des animaux HPHG, probablement en perturbant le processus d`activation de la lipolyse.

Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines

Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1 beta, IL-23, IL-6 and TGF-beta) were detected by immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.

Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin

The human blood fluke Schistosoma mansoni is the primary cause of schistosomiasis, a debilitating disease that affects 200 million individuals in over 70 countries. The biogenic amine serotonin is essential for the survival of the parasite and serotonergic proteins are potential novel drug targets for treating schistosomiasis. Here we characterize two novel serotonin transporter gene transcripts, SmSERT-A and SmSERT-B, from S. mansoni. Southern blot analysis shows that the two mRNAs are the products of different alleles of a single SmSERT gene locus. The two SmSERT forms differ in three amino acid positions near the N-terminus of the protein. Both SmSERTs are expressed in the adult form and in the sporocyst form (infected snails) of the parasite, but are absent from all other stages of the parasite`s complex life cycle. Heterologous expression of the two cDNAs in mammalian cells resulted in saturable, sodium-dependent serotonin transport activity with an apparent affinity for serotonin comparable to that of the human serotonin transporter. Although the two SmSERTs are pharmacologically indistinguishable from each other, efflux experiments reveal notably higher substrate selectivity for serotonin compared with their mammalian counterparts. Several well-established substrates for human SERT including (+/-)MDMA, S-(+)amphetamine, RU 24969, and m-CPP are not transported by SmSERTs, underscoring the higher selectivity of the schistosomal isoforms. Voltage-clamp recordings of SmSERT substrate-elicited currents confirm the substrate selectivity observed in efflux experiments and suggest that it may be possible to exploit the electrogenic nature of SmSERT to screen for compounds that target the parasite in vivo. (C) 2009 Elsevier B.V. All rights reserved.

Analysis of Detergent-Insoluble and Whole Cell Lysate Fractions of Resting Neutrophils Using High-Resolution Mass Spectrometry

Neutrophilic granulocytes play a major role in the initiation and resolution of the inflammatory response, and demonstrate significant transcriptional and translational activity. Although much was known about neutrophils prior to the introduction of proteomics, the use of MS-based methodologies has provided an unprecedented tool to confirm and extend previous findings. In the present study, we performed a Gel-LC-MS/MS analysis of neutrophil detergent insoluble and whole cell lysate fractions of resting neutrophils. We achieved a set of identifications through the use of high-resolution mass spectrometry and validation of its data. We identified a total of 1249 proteins with a wide range of intensities from both detergent-insoluble and whole cell lysate fractions, allowing a mapping of proteins such as those involved in intracellular transport (Rab and Sec family proteins) and cell signaling (S100 proteins). These results represent the most comprehensive proteomic characterization of resting human neutrophils to date, and provide important information relevant for further studies of the immune system in health and disease. The methods applied here can be employed to help us understand how neutrophils respond to various physiologic and pathophysiologic conditions and could be extended to protein quantitation after cell activation.

Quartz Crystal Microbalance monitoring the real-time binding of lectin with carbohydrate with high and low molecular mass

Quartz Crystal Microbalance (QCM) was used to monitor the mass changes on a quartz crystal surface containing immobilized lectins that interacted with carbohydrates. The strategy for lectin immobilization was developed on the basis of a multilayer system composed of Au-cystamine-glutaraldehyde-lectin. Each step of the immobilization procedure was confirmed by FTIR analysis. The system was used to study the interactions of Concanavalin A (ConA) with maltose and Jacalin with Fetuin. The real-time binding of different concentrations of carbohydrate to the immobilized lectin was monitored by means of QCM measurements and the data obtained allowed for the construction of Langmuir isotherm curves. The association constants determined for the specific interactions analyzed here were (6.4 +/- 0.2) X 10(4) M-1 for Jacalin-Fetuin and (4.5 +/- 0.1) x 10(2) M-1 for ConA-maltose. These results indicate that the QCM constitutes a suitable method for the analysis of lectin-carbohydrate interactions, even when assaying low molecular mass ligands such as disaccharides. Published by Elsevier B.V.

High-voltage electrical burn injuries: Functional upper extremity assessment

High-voltage electric injuries have many manifestations, and an important complication is the damage of the central/peripheral nervous system. The purpose of this work was to assess the upper limb dysfunction in patients injured by high-voltage current. The evaluation consisted of analysis of patients` records, cutaneous-sensibility threshold, handgrip and pinch strength and a specific questionnaire about upper limb dysfunctions (DASH) in 18 subjects. All subjects were men; the average age at the time of the injury was 38 years. Of these, 72% changed job/retired after the injury. The current entrance was the hand in 94% and grounding in the lower limb in 78%. The average burned surface area (BSA) was 8.6%. The handgrip strength of the injured limb was reduced (p < 0.05) and so also that of the three pinch types. The relationship between the handgrip strength and the DASH was statistically significant (p < 0.001) as well as the relationship between the three pinch types (p <= 0.02) to the injured limb. The ability to perceive cutaneous touch/pressure was decreased in the burnt hand, principally in the median nerve area. These data indicate a reduction of the hand muscular strength and sensibility, reducing the function of the upper limb in patients who received high-voltage electrical shock. (C) 2008 Elsevier Ltd and ISBI. All rights reserved.