Depression, glycemic control and type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Comorbid depression in diabetes has been suggested as one of the possible causes of an inadequate glycemic control. The purpose of this study was to investigate the association between major depression and the glycemic control of type 2 diabetes mellitus (T2DM).</p> <p>Methods</p> <p>Seventy T2DM patients were evaluated. They underwent a psychiatric examination using the following instruments: Structured Clinical Interview for DSM-IV and Beck Depression Inventory. The diabetes status was assessed in the short-term (glycemia, glycated hemoglobin) clinical control.</p> <p>Results</p> <p>The presence of current depression was observed in 18.6% (13/70). In addition, type 2 diabetes patients who displayed depression evidenced higher levels of glycated hemoglobin (8.6 ± 2.0 vs. 7.5 ± 1.8; p = 0.05) when compared to those who did not exhibit a mood disorder.</p> <p>Conclusions</p> <p>In our sample, the presence of depression seems to impact on the short-term control of T2DM. The authors discuss the clinical utility of these findings in the usual treatment of diabetes.</p

Paper-based platform with an in situ molecularly imprinted polymer for ß-amyloid

Alzheimers disease (AD) is one of the most common forms of dementia affecting millions of people worldwide. Currently, an easy and effective form of diagnosis is missing, which significantly hinders a possible improvement of the patients quality of life. In this context, biosensors emerge as a future solution, opening the doors for preventive medicine and allowing the premature diagnosis of numerous pathologies. This work presents a pioneering biosensor that combines a bottom-up design approach using paper as a platform for the electrochemical recognition of peptide amyloid -42 (A-42), a biomarker for AD present in blood, associated with visible differences in the brain tissue and responsible for the formation of senile plaques. The sensor layer relies on a molecularly imprinted polymer as a biorecognition element, created on the carbon ink electrodes surface by electropolymerizing a mixture of the target analyte (A-42) and a monomer (O-phenylenediamine) at neutral pH 7.2. Next, the template molecule was removed from the polymeric network by enzymatic and acidic treatments. The vacant sites so obtained preserved the shape of the imprinted protein and were able to rebind the target analyte. Morphological and chemical analyses were performed in order to control the surface modification of the materials. The analytical performance of the biosensor was evaluated by an electroanalytical technique, namely, square wave voltammetry. For this purpose, the analytical response of the biosensor was tested with standard solutions ranging from 0.1 ng/mL to 1 g/mL of A-42. The linear response of the biosensor went down to 0.1 ng/mL. Overall, the developed biosensor offered numerous benefits, such as simplicity, low cost, reproducibility, fast response, and repeatability less than 10%. All together, these features may have a strong impact in the early detection of AD.The authors acknowledge funding from project PTDC/AAGTEC/5400/2014, POCI-01-0145-FEDER-016637, POCI-01-0145-FEDER-007688, and UID/CTM/50025/2019 funded by European funds through FEDER (European Funding or Regional Development) via COMPETE2020 - POCI (operational program for internationalization and competitively) by national funding through the National Foundation for Science and Technology, I.P. (FCT-MCTES). Additionally, they are grateful to the project IBEROS, Instituto de Bioingenieria en Red para el Envejecimiento Saludable, POCTEP/0245-BEROS-1-E, PROGRAMA INTERREG 2014-2020 funded through FEDER within the cooperation region of Galiza/Spain and North of Portugal. A.C.M. and F.T.C.M. gratefully acknowledges FCT-MCTES for the financial support (PhD grant reference SFRH/BD/115173/2016 intituled “Nanobiosensing platform based on MIP-SERS for breast cancer exosome characterization and detection” and Post-Doc grant reference SFRH/BPD/97891/2013 intituled “Biomedical devices for easier and quicker screening procedures of the Alzheimer’s). This work is part of the Master Thesis in Micro and Nanotechnology Engineering defended by Marta V. Pereira. at FCT NOVA titled “Fabrication of 3D electrodes for biosensor applications” in December 2018.info:eu-repo/semantics/publishedVersio

Towards a genome-wide transcriptogram: the Saccharomyces cerevisiae case

A genome modular classification that associates cellular processes to modules could lead to a method to quantify the differences in gene expression levels in different cellular stages or conditions: the transcriptogram, a powerful tool for assessing cell performance, would be at hand. Here we present a computational method to order genes on a line that clusters strongly interacting genes, defining functional modules associated with gene ontology terms. The starting point is a list of genes and a matrix specifying their interactions, available at large gene interaction databases. Considering the Saccharomyces cerevisiae genome we produced a succession of plots of gene transcription levels for a fermentation process. These plots discriminate the fermentation stage the cell is going through and may be regarded as the first versions of a transcriptogram. This method is useful for extracting information from cell stimuli/responses experiments, and may be applied with diagnostic purposes to different organisms

Effects of vitamin D supplementation on pulmonary function in postmenopausal women following an aquatic exercise program

Objective: This study sought to investigate the effects of vitamin D supplementation and aquatic exercise on pulmonary function in postmenopausal women. Materials and methods: This prospective and controlled study included 104 women (62 +/- 6.5 years) divided into three groups: a control group lacking vitamin D and calcium supplementation which remained sedentary (CGn = 17)a control group receiving vitamin D and calcium supplementation which remained sedentary (CDG, n = 33)and a group that completed aquatic exercises three times a week and received vitamin D and calcium supplementation (DTG, n = 54). Data before and after 6 months of the study were analyzed, including serum 25-hydroxyvitamin D (25(OH) D) and calcium concentrations, peak expiratory flow (PEF), forced vital capacity (FVC), and cirtometry. Results: We observed significant increases in 25(OH) D concentrations in CDG (52.9 +/- 2.4 to 69.1 +/- 2.2nmol/Lp < 0.0001) and DTG groups (55.5 +/- 3 to 71.5 +/- 3 nmol/Lp < 0.0001). PEF increased by 7 +/- 2% (p = 0.0080) in CDG group and 11 +/- 2% (p < 0.0001) in DTG group, whereas FVC increased by 7 +/- 2% (p = 0.0016) in the CDG group and 10 +/- 2% (p < 0.0001) in the DTG group, whereas CG had no changes in any of these parameters. The increment value of cirtometry in DTG group (+ 43 +/- 3%) were significantly (p < 0.0001) higher than those in CG (-4 +/- 8%) and CDG (+ 4 +/- 9%) groups. Conclusion: Our data suggest that vitamin D supplementation improves pulmonary function parameters in postmenopausal women.Fapesp (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Federal AgencFederal Agency for Support and Evaluation of Graduate Education (Higher Education Personnel Improvement Coordination - Capes)Univ Fed Sao Paulo, Dept Med, Disciplina Endocrinol, Fac Med,Unifesp,EPM, Sao Paulo, SP, BrazilUniv Sao Judas Tadeu, Fisiol Translac, Programa Posgrad Educ Fis & Ciencias Envelhecimen, Sao Paulo, SP, BrazilUniv Sao Paulo, Escola Educ Fis & Esporte, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Endocrinol, Fac Med,Unifesp,EPM, Sao Paulo, SP, BrazilFAPESP: 08/50179-9Web of Scienc

O impacto da poliquimioterapia no perfil epidemiológico da hanseníase em Juiz de Fora, Brasil

We investigated the impact of multidrug therapy (MDT) on the epidemiological pattern of leprosy in Juiz de Fora, Brazil, from 1978 to 1995. Evaluation of 1,283 medical charts was performed according to the treatment regimen used in two different periods. Following the introduction of MDT in 1987, prevalence of leprosy decreased from 22 patients/10,000 inhabitants to 5.2 patients/10,000 inhabitants in 1995. Incidence rate of leprosy was lower in period II (1987-1995) than in period I (1978-1986). Decreasing prevalence and incidence appear to be related to drug efficacy rather than decreased case identification, since both self-referred and professionally referred treatment increased markedly from period I to period II. For both periods, multibacillary leprosy was the most frequent clinical form of the disease (±68%), and the main infection risk factor identified was household contact. Leprosy is predominantly manifested in adults, but an increase in the number of very old and very young patients was observed in period II. The MDT program has been effective both in combating leprosy and in promoting awareness of the disease.Investigamos o impacto da poliquimioterapia (PQT) no perfil epidemiológico da hanseníase em Juiz de Fora, Brasil, de 1978 a 1995. Fizemos uma avaliação de 1.283 prontuários, de acordo com o esquema terapêutico adotado em dois diferentes períodos. Desde a introdução da PQT, em 1987, a prevalência da hanseníase caiu de 22 pacientes/dez mil habitantes para 5,2 pacientes/dez mil habitantes em 1995. A incidência da doença foi menor no período II (1987-1995) em comparação ao período I (1978-1986). A diminuição da prevalência e da incidência está mais relacionada à eficácia das drogas que a uma queda na identificação da infecção, já que tanto a procura espontânea quanto os encaminhamentos aumentaram significativamente do período I para o período II. Em ambos os períodos, a forma clínica mais freqüente foi a multibacilar (±68%), e o contato intradomicilicar foi o maior fator de risco conhecido associado à infecção. Um aumento de pacientes muito velhos ou muito novos foi observado no período II. Os resultados indicam que o esquema PQT tem sido eficaz no combate à hanseníase e tem aumentado a conscientização e o conhecimento da doença

Genetic transformation of novel isolates of chicken Lactobacillus bearing probiotic features for expression of heterologous proteins: a tool to develop live oral vaccines

BACKGROUND: The use of lactic acid bacteria as vehicles to delivery antigens to immunize animals is a promising issue. When genetically modified, these bacteria can induce a specific local and systemic immune response against selected pathogens. Gastric acid and bile salts tolerance, production of antagonistic substances against pathogenic microorganisms, and adhesive ability to gut epithelium are other important characteristics that make these bacteria useful for oral immunization. RESULTS: Bacteria isolated on de Man, Rogosa and Sharpe medium (MRS) from different gastrointestinal portions of broiler chicks were evaluated for their resistance to artificial gastric acid and bile salts, production of hydrogen peroxide, and cell surface hydrophobicity. Thirty-eight isolates were first typed at species level by PCR amplification of 16S-23S rRNA intergenic spacers using universal primers that anneal within 16S and 23S genes, followed by restriction digestion analyses of PCR amplicons (PCR-ARDRA). An expression cassette was assembled onto the pCR2.1-Topo vector by cloning the promoter, leader peptide, cell wall anchor and terminator sequences derived from the laminin binding S-layer protein gene of L. crispatus strain F5.7 (lbs gene). A sequence encoding the green fluorescent protein (GFP) was inserted as reporter gene, and an erythromycin resistance gene was added as selective marker. All constructs were able to express GFP in the cloning host E. coli XL1-Blue and different Lactobacillus strains as verified by FACS and laser scanning confocal microscopy. CONCLUSION: Lactobacillus isolated from gastrointestinal tract of broiler chickens and selected for probiotic characteristics can be genetically modified by introducing an expression cassette into the lbs locus. The transformed bacteria expressed on its cell wall surface different fluorescent proteins used as reporters of promoter function. It is possible then that similar bacterial model expressing pathogen antigens can be used as live oral vaccines to immunize broilers against infectious diseases

Intensity modulated radiotherapy for localized prostate cancer: rigid compliance to dose-volume constraints as a warranty of acceptable toxicity?

BACKGROUND: To report the toxicity after intensity modulated radiotherapy (IMRT) for patients with localized prostate cancer, as a sole treatment or after radical prostatectomy. METHODS: Between August 2001 and December 2003, 132 patients with prostate cancer were treated with IMRT and 125 were evaluable to acute and late toxicity analysis, after a minimum follow-up time of one year. Clinical and treatment data, including normal tissue dose-volume histogram (DVH) constraints, were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1 months. RESULTS: From the 125 patients, 73 (58.4%) presented acute Grade 1 or Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3 GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26 patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity, respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2 GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of treatment plans. On univariate analysis, no significant risk factor was identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was associated to higher Grade 2 GU late toxicity (p = 0.042). CONCLUSION: IMRT is a well tolerable technique for routine treatment of localized prostate cancer, with short and medium-term acceptable toxicity profiles. According to the data presented here, rigid compliance to DHV constraints might prevent higher incidences of normal tissue complication

Unique PFK regulatory property from some mosquito vectors of disease, and from Drosophila melanogaster

Effect of F2, 6BP on Aedes aegypti PFK activity. PFK activity was measured at pH = 7.4, 1 mM F6P, 5 mM ATP at several F2, 6BP concentrations (0.01–50 μM). Values are the means ± SEM of three independent experiments. (TIF 466 kb

One-year timeline kinetics of cytokine-mediated cellular immunity in dogs vaccinated against visceral leishmaniasis

BACKGROUND: The main control strategy for visceral leishmaniasis in Brazil has been based on the elimination of seropositive dogs, although this is not widely accepted. In this context, the use of a long-lasting protective vaccine against canine visceral leishmaniasis (CVL) has been highly expected. The aim of this work was to determine the timeline kinetics of the cytokine microenvironment derived from circulating leukocytes as supportive immunological biomarkers triggered by Leishmune® vaccine. Cross-sectional kinetic analysis of cellular immunity cytokines was carried out at three times (1, 6 and 12 months) after primovaccination with Leishmune®. In vitro short-term whole blood cultures were stimulated with Leishmania infantum soluble antigen (SLAg). The secreted cytokine signatures and their major sources were determined. RESULTS: At six months after vaccination, Leishmune® induced an increase in IL-8, IFN-γ, IL-17a and TNF-α levels and a decrease in IL-10. Cytokine signature analysis revealed a shift in the microenvironment towards a pro-inflammatory profile mediated by IL-8 and IFN-γ. Both, CD4(+) (↑TNF-α(+) and ↑IFN-γ (+)) and CD8(+) (↑IL-17a and ↓IL-4) T-cells contributed to the acquired immune responses observed after stimulation with SLAg. CONCLUSIONS: The changes observed in the cytokine profile suggested that Leishmune® was able to induce an effective response at six months after primovaccination. After one year, it returned to baseline suggesting the need of additional boosting

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD –, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icv injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZ-induced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD