Comparison of baseline correction algorithms for in vivo 1H-MRS.

Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short-echo-time MRS data. In short-echo-time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long-echo-time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi-LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm-QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm-QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting.

Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder.

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex-a key region of the DMN-between patients with ADHD and controls. Five brain metabolites-glutamate, inositol, N-acetyl aspartate, choline, and creatine-were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0 T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

Cobertura de MRS e indicación de terapia hormonal en Pedro Aguirre Cerda, septiembre de 2019 / MRS coverage and hormone replacement therapy indication at Pedro Aguirre Cerda, September 2019

Introducción: El envejecimiento de la población en todo el mundo es un fenómeno progresivo y Chile no se queda atrás frente a esto. Actualmente existe un subprograma de climaterio mujeres entre los 45 a 64 años, que presenta diversas acciones y propósitos. Objetivo: Describir la cobertura de la aplicación de la Menopause Rating Scale (MRS) e indicación de terapia de reemplazo hormonal en mujeres inscritas en los CESFAM de la comuna de Pedro Aguirre Cerda. Método: Descriptivo transversal. Resultados: La cobertura de aplicación de MRS en mujeres entre 45-64 años fue de un 62,6%. Un 34,3% de mujeres presentaron un puntaje MRS alterado, indicándose terapia hormonal en un 37,8% de los casos, en las indicaciones un 21,8% eran usuarias candidatas acorde a criterios médicos y un 78,2% no lo eran. Conclusiones: Se debe aumentar la cobertura de MRS y recursos para exámenes de laboratorio, de imágenes y capacitaciones, esto para mejorar la entrega de las prestaciones en el subprograma climaterio.

Introduction: The aging of the population worldwide is a progressive phenomenon and Chile is not lagging behind in this. Currently, there is a climacteric subprogram for women between 45 and 64 years of age, which has various actions and purposes. Objective: To describe the coverage of the application of the Menopause Rating Scale (MRS) and indication of hormone replacement therapy in women enrolled in the CESFAM of the commune of Pedro Aguirre Cerda. Method: Cross-sectional descriptive study. Results: The coverage of the MRS application in women between 45-64 years old was 62.6%. A 34.3% of women presented an altered MRS score, indicating hormone therapy in 37.8% of the cases, 21.8% of the indications were candidates according to medical criteria and 78.2% were not. Conclusions: There is a lack of labs and images tests in the climacteric controls, resulting in a mayor number of women no candidates to the hormonal therapy according to medical criteria.

A2BAR Antagonism Decreases the Glomerular Expression and Secretion of Chemoattractants for Monocytes and the Pro-Fibrotic M2 Macrophages Polarization during Diabetic Nephropathy.

Some chemoattractants and leukocytes such as M1 and M2 macrophages are known to be involved in the development of glomerulosclerosis during diabetic nephropathy (DN). In the course of diabetes, an altered and defective cellular metabolism leads to the increase in adenosine levels, and thus to changes in the polarity (M1/M2) of macrophages. MRS1754, a selective antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerulosclerosis and decreased macrophage-myofibroblast transition in DN rats. Therefore, we aimed to investigate the effect of MRS1754 on the glomerular expression/secretion of chemoattractants, the intraglomerular infiltration of leukocytes, and macrophage polarity in DN rats. Kidneys/glomeruli of non-diabetic, DN, and MRS1754-treated DN rats were processed for transcriptomic analysis, immunohistopathology, ELISA, and in vitro macrophage migration assays. The transcriptomic analysis identified an upregulation of transcripts and pathways related to the immune system in the glomeruli of DN rats, which was attenuated using MRS1754. The antagonism of the A2BAR decreased glomerular expression/secretion of chemoattractants (CCL2, CCL3, CCL6, and CCL21), the infiltration of macrophages, and their polarization to M2 in DN rats. The in vitro macrophages migration induced by conditioned-medium of DN glomeruli was significantly decreased using neutralizing antibodies against CCL2, CCL3, and CCL21. We concluded that the pharmacological blockade of the A2BAR decreases the transcriptional expression of genes/pathways related to the immune response, protein expression/secretion of chemoattractants, as well as the infiltration of macrophages and their polarization toward the M2 phenotype in the glomeruli of DN rats, suggesting a new mechanism implicated in the antifibrotic effect of MRS1754.

The safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke: A systematic meta-analysis.

BACKGROUND: Stroke is a major global public health problem, affecting 13.7 million people worldwide. Previous studies have found a neuroprotective effect of hypothermia therapy and the efficacy and safety of combined hypothermia and mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke have also attracted attention. OBJECTIVE: In the present research, the authors conducted a meta-analysis to comprehensively assess the safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke. METHODS: Articles published from January 2001 to May 2022 were searched from Google Scholar, Baidu Scholar and PubMed to evaluate the clinical significance of hypothermia treatment in ischemic stroke. Complications, short-term mortality, and the modified Rankin Scale (mRS) in the full text was extracted. RESULTS: 89 publications were selected and 9 among them were included in this study with sample size of 643. All selected studies are in accordance with the inclusion criteria. Forest plot of clinical characteristics was as follows: complications (RR = 1.132, 95% CI 0.942‒1.361, p = 0.186, I2 = 37.2%), mortality within 3 months (RR = 1.076, 95% CI 0.694‒1.669, p = 0.744, I2 = 0.00%), mRS ≤ 1 at 3 months (RR = 1.138, 95% CI 0.829‒1.563, p = 0.423, I2 = 26.0%), mRS ≤ 2 at 3 months (RR = 1.672, 95% CI 1.236‒2.263, p = 0.001, I2=49.6%) and mRS ≤ 3 at 3 months (RR = 1.518, 95% CI 1.128‒2.043, p = 0.006, I2 = 0.00%). The funnel plot suggested that there was no significant publication bias in the meta-analysis on complications, mortality within 3 months, mRS ≤ 1 at 3 months and mRS ≤ 2 at 3 months. CONCLUSION: In summary, the results showed that hypothermia treatment was correlated with mRS ≤ 2 at 3 months, but not linked with complications and mortality within 3 months.

BDNF rs6265 differentially influences neurometabolites in the anterior cingulate of healthy and bipolar disorder subjects.

Brain-derived neurotrophic factor (BDNF) is the most abundant brain neurotrophin and plays a critical role in neuronal growth, survival and plasticity, implicated in the pathophysiology of Bipolar Disorders (BD). The single-nucleotide polymorphism in the BDNF gene (BDNF rs6265) has been associated with decreased hippocampal BDNF secretion and volume in met carriers in different populations, although the val allele has been reported to be more frequent in BD patients. The anterior cingulate cortex (ACC) is a key center integrating cognitive and affective neuronal connections, where consistent alterations in brain metabolites such as Glx (Glutamate + Glutamine) and N-acetylaspartate (NAA) have been consistently reported in BD. However, little is known about the influence of BDNF rs6265 on neurochemical profile in the ACC of Healthy Controls (HC) and BD subjects. The aim of this study was to assess the influence of BDNF rs6265 on ACC neurometabolites (Glx, NAA and total creatine- Cr) in 124 euthymic BD type I patients and 76 HC, who were genotyped for BDNF rs6265 and underwent a 3-Tesla proton magnetic resonance imaging and spectroscopy scan (1 H-MRS) using a PRESS ACC single-voxel (8cm3) sequence. BDNF rs6265 polymorphism showed a significant two-way interaction (diagnosis × genotype) in relation to NAA/Cr and total Cr. While met carriers presented increased NAA/Cr in HC, BD-I subjects with the val allele revealed higher total Cr, denoting an enhanced ACC metabolism likely associated with increased glutamatergic metabolites observed in BD-I val carriers. However, these results were replicated only in men. Therefore, our results support evidences that the BDNF rs6265 polymorphism exerts a complex pleiotropic effect on ACC metabolites influenced by the diagnosis and sex.

The safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke: A systematic meta-analysis

Abstract Background Stroke is a major global public health problem, affecting 13.7 million people worldwide. Previous studies have found a neuroprotective effect of hypothermia therapy and the efficacy and safety of combined hypothermia and mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke have also attracted attention. Objective In the present research, the authors conducted a meta-analysis to comprehensively assess the safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke. Methods Articles published from January 2001 to May 2022 were searched from Google Scholar, Baidu Scholar and PubMed to evaluate the clinical significance of hypothermia treatment in ischemic stroke. Complications, short-term mortality, and the modified Rankin Scale (mRS) in the full text was extracted. Results 89 publications were selected and 9 among them were included in this study with sample size of 643. All selected studies are in accordance with the inclusion criteria. Forest plot of clinical characteristics was as follows: complications (RR = 1.132, 95% CI 0.942‒1.361, p = 0.186, I2= 37.2%), mortality within 3 months (RR = 1.076, 95% CI 0.694‒1.669, p = 0.744, I2= 0.00%), mRS ≤ 1 at 3 months (RR = 1.138, 95% CI 0.829‒1.563, p = 0.423, I2= 26.0%), mRS ≤ 2 at 3 months (RR = 1.672, 95% CI 1.236‒2.263, p = 0.001, I2=49.6%) and mRS ≤ 3 at 3 months (RR = 1.518, 95% CI 1.128‒2.043, p = 0.006, I2= 0.00%). The funnel plot suggested that there was no significant publication bias in the meta-analysis on complications, mortality within 3 months, mRS ≤ 1 at 3 months and mRS ≤ 2 at 3 months. Conclusion In summary, the results showed that hypothermia treatment was correlated with mRS ≤ 2 at 3 months, but not linked with complications and mortality within 3 months.

Emerging findings of glutamate-glutamine imbalance in the medial prefrontal cortex in attention deficit/hyperactivity disorder: systematic review and meta-analysis of spectroscopy studies.

One of the main challenges in investigating the neurobiology of ADHD is our limited capacity to study its neurochemistry in vivo. Magnetic resonance spectroscopy (MRS) estimates metabolite concentrations within the brain, but approaches and findings have been heterogeneous. To assess differences in brain metabolites between patients with ADHD and healthy controls, we searched 12 databases screening for MRS studies. Studies were divided into 'children and adolescents' and 'adults' and meta-analyses were performed for each brain region with more than five studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. Thirty-three studies met our eligibility criteria, including 874 patients with ADHD. Primary analyses revealed that the right medial frontal area of children with ADHD presented higher concentrations of a composite of glutamate and glutamine (p = 0.02, SMD = 0.53). Glutamate might be implicated in pruning and neurodegenerative processes as an excitotoxin, while glutamine excess might signal a glutamate depletion that could hinder neurotrophic activity. Both neuro metabolites could be implicated in the differential cortical thinning observed in patients with ADHD across all ages. Notably, more homogeneous designs and reporting guidelines are the key factors to determine how suitable MRS is for research and, perhaps, for clinical psychiatry. Results of this meta-analysis provided an overall map of the brain regions evaluated so far, addressed the role of glutamatergic metabolites in the pathophysiology of ADHD, and pointed to new perspectives for consistent use of the tool in the field.

Attention-deficit/hyperactivity disorder and brain metabolites from proton magnetic resonance spectroscopy: a systematic review and meta-analysis protocol

Abstract Despite major advances in the study of the brain, investigations on neurochemistry in vivo still lack the solid ground of more established methods, such as structural and functional magnetic resonance imaging. Proton magnetic resonance spectroscopy (MRS) is a technique that might potentially fill in this gap. Nevertheless, studies using this approach feature great methodological heterogeneity, such as varying voxel of choice, differences on emphasized metabolites, and absence of a standardized unit. In this study, we present a methodology for creating a systematic review and meta-analysis for this kind of scientific evidence using the prototypical case of attention-deficit/hyperactivity disorder. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42018112418.

Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A 1H magnetic resonance spectroscopy study.

BACKGROUND: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. OBJECTIVE: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. METHODS: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. RESULTS: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. CONCLUSION: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.

Detection of the main multiresistant microorganisms in the environment of a teaching veterinary hospital in Brazil / Detecção dos principais microrganismos multirresistentes no ambiente de um hospital veterinário de ensino no Brasil

Contamination of the veterinary hospital environment with multiresistant pathogens endangers not only hospitalized animals, but also the workplace safety of veterinarians and nurses, animal guardians and, when in case of a teaching hospital, veterinary students. The objective of this study was to map the main points of bacterial contamination of a veterinary teaching hospital in Brazil to identify multiresistant microorganisms and their antimicrobial resistance genes. Samples were collected from 39 different locations of a veterinary school hospital which comprised a pool according to each hospital environment. In certain environments, more than one pool has been collected. All samples were collected in quadruplicates for the selective isolation of the main multiresistant microorganisms: methicillin-resistant Staphylococcus (MRS), vancomycin resistant Enterococcus (VRE), cephalosporinases and/or extended-spectrum beta-lactamase-producing Gram-negative bacteria (ESBL) and Carbapenemase-producing (CP). After isolation and identification of isolates, multiplex-PCR reactions were performed to detect the main genes for each microorganism and antimicrobial susceptibility tests with the main antibiotics used for each bacterial group according to CLSI. Of the 39 veterinary teaching hospital sites collected, all (100%) had at least one of the microorganisms surveyed, and 17.95% (n=7) of the sites were able to isolate the four pathogens. From the 94 pools collected, it was possible to isolate MRS in 81.91% (n=77), VRE in 12.77% (n=12), cephalosporinases and/or ESBL in 62.77% (n=59) and CP in 24.47%. (n=23). Regarding MRS, the mecA gene was detected in all isolates. All isolated VREs were identified as Enterococcus faecalis and presented the vanA gene. Regarding cephalosporinases and/or ESBL, 89.83% (n=53) of the isolates presented the blaTEM gene, 57.63% (n=34) the blaOXA-1 gene, 37.29% (n=22) blaCTX-M gene from some group (1, 2, 9 ou 8/25) and 20.34% (n=12) the blaSHV gene. It was possible to identify the main microorganisms responsible for causing nosocomial infections in humans (VRE, MRS, ESBL and CP) in the veterinary hospital environment, suggesting a source of infection for professionals and students of veterinary medicine, placing a high risk for public health.(AU)

A contaminação do ambiente hospitalar veterinário com patógenos multirresistentes coloca em perigo não apenas os animais hospitalizados, mas também a segurança no local de trabalho de veterinários e enfermeiros, responsáveis por animais e, quando se tratar de um hospital de ensino, estudantes de veterinária. O objetivo deste estudo foi mapear os principais pontos de contaminação bacteriana de um hospital veterinário de ensino no Brasil, identificando microorganismos multirresistentes e seus genes de resistência antimicrobiana. As amostras foram coletadas em 39 locais diferentes de um hospital de escola veterinária, que compreendia um pool de acordo com o ambiente de cada hospital. Em certos ambientes, mais de um pool foi coletado. Todas as amostras foram coletadas em quadruplicados para o isolamento seletivo dos principais microorganismos multirresistentes: Staphylococcus resistente à meticilina (MRS), Enterococcus resistente à vancomicina (VRE), bactérias Gram-negativas produtoras de cefalosporinases e/ou beta-lactamase de espectro estendido (ESBL) e produtoras de carbapenemase (PC). Após o isolamento e identificação dos isolados, foram realizadas reações de PCR multiplex para detectar os principais genes de cada microorganismo e testes de susceptibilidade a antimicrobianos com os principais antibióticos utilizados para cada grupo bacteriano de acordo com o CLSI. Dos 39 locais do VCH coletados, todos (100%) possuíam pelo menos um dos microrganismos pesquisados e 17,95% (n=7) dos locais foram capazes de isolar os quatro patógenos. Dos 94 pools coletados, foi possível isolar MRS em 81,91% (n=77), VRE em 12,77% (n=12), ESBL em 62,77% (n=59) e carbapenemases em 24,47% (n=23). Em relação ao MRS, o gene mecA foi detectado em todos os isolados. Todos os VREs isolados foram identificados como Enterococcus faecalis e apresentaram o gene vanA. Em relação às cefalosporinases e/ou ESBL, 89,83% (n=53) dos isolados apresentaram o gene blaTEM, 57,63% (n=34) o gene blaOXA-1, 37,29% (n=22) o gene blaCTX-M de algum grupo e 20,34% (n=12) o gene blaSHV. Foi possível identificar os principais microrganismos responsáveis por causar infecções nosocomiais em humanos (VRE, MRS, ESBL e CP) no ambiente hospitalar veterinário, sugerindo uma fonte de infecção para profissionais e estudantes de medicina veterinária, colocando alto risco para a saúde pública.(AU)

Detection of the main multiresistant microorganisms in the environment of a teaching veterinary hospital in Brazil / Detecção dos principais microrganismos multirresistentes no ambiente de um hospital veterinário de ensino no Brasil

Contamination of the veterinary hospital environment with multiresistant pathogens endangers not only hospitalized animals, but also the workplace safety of veterinarians and nurses, animal guardians and, when in case of a teaching hospital, veterinary students. The objective of this study was to map the main points of bacterial contamination of a veterinary teaching hospital in Brazil to identify multiresistant microorganisms and their antimicrobial resistance genes. Samples were collected from 39 different locations of a veterinary school hospital which comprised a pool according to each hospital environment. In certain environments, more than one pool has been collected. All samples were collected in quadruplicates for the selective isolation of the main multiresistant microorganisms: methicillin-resistant Staphylococcus (MRS), vancomycin resistant Enterococcus (VRE), cephalosporinases and/or extended-spectrum beta-lactamase-producing Gram-negative bacteria (ESBL) and Carbapenemase-producing (CP). After isolation and identification of isolates, multiplex-PCR reactions were performed to detect the main genes for each microorganism and antimicrobial susceptibility tests with the main antibiotics used for each bacterial group according to CLSI. Of the 39 veterinary teaching hospital sites collected, all (100%) had at least one of the microorganisms surveyed, and 17.95% (n=7) of the sites were able to isolate the four pathogens. From the 94 pools collected, it was possible to isolate MRS in 81.91% (n=77), VRE in 12.77% (n=12), cephalosporinases and/or ESBL in 62.77% (n=59) and CP in 24.47%. (n=23). Regarding MRS, the mecA gene was detected in all isolates. All isolated VREs were identified as Enterococcus faecalis and presented the vanA gene. Regarding cephalosporinases and/or ESBL, 89.83% (n=53) of the isolates presented the blaTEM gene, 57.63% (n=34) the blaOXA-1 gene, 37.29% (n=22) blaCTX-M gene from some group (1, 2, 9 ou 8/25) and 20.34% (n=12) the blaSHV gene. It was possible to identify the main microorganisms responsible for causing nosocomial infections in humans (VRE, MRS, ESBL and CP) in the veterinary hospital environment, suggesting a source of infection for professionals and students of veterinary medicine, placing a high risk for public health.(AU)

A contaminação do ambiente hospitalar veterinário com patógenos multirresistentes coloca em perigo não apenas os animais hospitalizados, mas também a segurança no local de trabalho de veterinários e enfermeiros, responsáveis por animais e, quando se tratar de um hospital de ensino, estudantes de veterinária. O objetivo deste estudo foi mapear os principais pontos de contaminação bacteriana de um hospital veterinário de ensino no Brasil, identificando microorganismos multirresistentes e seus genes de resistência antimicrobiana. As amostras foram coletadas em 39 locais diferentes de um hospital de escola veterinária, que compreendia um pool de acordo com o ambiente de cada hospital. Em certos ambientes, mais de um pool foi coletado. Todas as amostras foram coletadas em quadruplicados para o isolamento seletivo dos principais microorganismos multirresistentes: Staphylococcus resistente à meticilina (MRS), Enterococcus resistente à vancomicina (VRE), bactérias Gram-negativas produtoras de cefalosporinases e/ou beta-lactamase de espectro estendido (ESBL) e produtoras de carbapenemase (PC). Após o isolamento e identificação dos isolados, foram realizadas reações de PCR multiplex para detectar os principais genes de cada microorganismo e testes de susceptibilidade a antimicrobianos com os principais antibióticos utilizados para cada grupo bacteriano de acordo com o CLSI. Dos 39 locais do VCH coletados, todos (100%) possuíam pelo menos um dos microrganismos pesquisados e 17,95% (n=7) dos locais foram capazes de isolar os quatro patógenos. Dos 94 pools coletados, foi possível isolar MRS em 81,91% (n=77), VRE em 12,77% (n=12), ESBL em 62,77% (n=59) e carbapenemases em 24,47% (n=23). Em relação ao MRS, o gene mecA foi detectado em todos os isolados. Todos os VREs isolados foram identificados como Enterococcus faecalis e apresentaram o gene vanA. Em relação às cefalosporinases e/ou ESBL, 89,83% (n=53) dos isolados apresentaram o gene blaTEM, 57,63% (n=34) o gene blaOXA-1, 37,29% (n=22) o gene blaCTX-M de algum grupo e 20,34% (n=12) o gene blaSHV. Foi possível identificar os principais microrganismos responsáveis por causar infecções nosocomiais em humanos (VRE, MRS, ESBL e CP) no ambiente hospitalar veterinário, sugerindo uma fonte de infecção para profissionais e estudantes de medicina veterinária, colocando alto risco para a saúde pública.(AU)

Detection of the main multiresistant microorganisms in the environment of a teaching veterinary hospital in Brazil

ABSTRACT: Contamination of the veterinary hospital environment with multiresistant pathogens endangers not only hospitalized animals, but also the workplace safety of veterinarians and nurses, animal guardians and, when in case of a teaching hospital, veterinary students. The objective of this study was to map the main points of bacterial contamination of a veterinary teaching hospital in Brazil to identify multiresistant microorganisms and their antimicrobial resistance genes. Samples were collected from 39 different locations of a veterinary school hospital which comprised a pool according to each hospital environment. In certain environments, more than one pool has been collected. All samples were collected in quadruplicates for the selective isolation of the main multiresistant microorganisms: methicillin-resistant Staphylococcus (MRS), vancomycin resistant Enterococcus (VRE), cephalosporinases and/or extended-spectrum beta-lactamase-producing Gram-negative bacteria (ESBL) and Carbapenemase-producing (CP). After isolation and identification of isolates, multiplex-PCR reactions were performed to detect the main genes for each microorganism and antimicrobial susceptibility tests with the main antibiotics used for each bacterial group according to CLSI. Of the 39 veterinary teaching hospital sites collected, all (100%) had at least one of the microorganisms surveyed, and 17.95% (n=7) of the sites were able to isolate the four pathogens. From the 94 pools collected, it was possible to isolate MRS in 81.91% (n=77), VRE in 12.77% (n=12), cephalosporinases and/or ESBL in 62.77% (n=59) and CP in 24.47%. (n=23). Regarding MRS, the mecA gene was detected in all isolates. All isolated VREs were identified as Enterococcus faecalis and presented the vanA gene. Regarding cephalosporinases and/or ESBL, 89.83% (n=53) of the isolates presented the blaTEM gene, 57.63% (n=34) the blaOXA-1 gene, 37.29% (n=22) blaCTX-M gene from some group (1, 2, 9 ou 8/25) and 20.34% (n=12) the blaSHV gene. It was possible to identify the main microorganisms responsible for causing nosocomial infections in humans (VRE, MRS, ESBL and CP) in the veterinary hospital environment, suggesting a source of infection for professionals and students of veterinary medicine, placing a high risk for public health.

RESUMO: A contaminação do ambiente hospitalar veterinário com patógenos multirresistentes coloca em perigo não apenas os animais hospitalizados, mas também a segurança no local de trabalho de veterinários e enfermeiros, responsáveis por animais e, quando se tratar de um hospital de ensino, estudantes de veterinária. O objetivo deste estudo foi mapear os principais pontos de contaminação bacteriana de um hospital veterinário de ensino no Brasil, identificando microorganismos multirresistentes e seus genes de resistência antimicrobiana. As amostras foram coletadas em 39 locais diferentes de um hospital de escola veterinária, que compreendia um pool de acordo com o ambiente de cada hospital. Em certos ambientes, mais de um pool foi coletado. Todas as amostras foram coletadas em quadruplicados para o isolamento seletivo dos principais microorganismos multirresistentes: Staphylococcus resistente à meticilina (MRS), Enterococcus resistente à vancomicina (VRE), bactérias Gram-negativas produtoras de cefalosporinases e/ou beta-lactamase de espectro estendido (ESBL) e produtoras de carbapenemase (PC). Após o isolamento e identificação dos isolados, foram realizadas reações de PCR multiplex para detectar os principais genes de cada microorganismo e testes de susceptibilidade a antimicrobianos com os principais antibióticos utilizados para cada grupo bacteriano de acordo com o CLSI. Dos 39 locais do VCH coletados, todos (100%) possuíam pelo menos um dos microrganismos pesquisados e 17,95% (n=7) dos locais foram capazes de isolar os quatro patógenos. Dos 94 pools coletados, foi possível isolar MRS em 81,91% (n=77), VRE em 12,77% (n=12), ESBL em 62,77% (n=59) e carbapenemases em 24,47% (n=23). Em relação ao MRS, o gene mecA foi detectado em todos os isolados. Todos os VREs isolados foram identificados como Enterococcus faecalis e apresentaram o gene vanA. Em relação às cefalosporinases e/ou ESBL, 89,83% (n=53) dos isolados apresentaram o gene blaTEM, 57,63% (n=34) o gene blaOXA-1, 37,29% (n=22) o gene blaCTX-M de algum grupo e 20,34% (n=12) o gene blaSHV. Foi possível identificar os principais microrganismos responsáveis por causar infecções nosocomiais em humanos (VRE, MRS, ESBL e CP) no ambiente hospitalar veterinário, sugerindo uma fonte de infecção para profissionais e estudantes de medicina veterinária, colocando alto risco para a saúde pública.

Occurrence of Methicillin-Resistant Staphylococcus spp. on Brazilian Dairy Farms that Produce Unpasteurized Cheese.

Methicillin-resistant Staphylococcus spp. (MRS) have been identified in several foods, including dairy products. Studies are needed about their occurrence and genetic diversity in the dairy production chain in order to gain a better understanding of their epidemiology and control. This study therefore focuses on isolating and characterizing MRS strains detected in milk used in the production of Brazilian artisanal unpasteurized cheeses. To this end, samples were collected from bovine feces, the hands of milkmen, milking buckets, sieves, unpasteurized milk, whey, water, artisanal unpasteurized cheeses, cheese processing surfaces, cheese handlers, cheese trays, cheese molds, and skimmers at five dairy farms located in the state of São Paulo, Brazil. Colonies suggestive of Staphylococcus spp. were subjected to multiplex PCR to confirm the presence of Staphylococcus aureus and to detect the mecA gene. Sixteen isolates containing mecA gene were detected in samples from unpasteurized cheese and from cheese handlers. None of these isolates were positive to enterotoxin genes. These 16 isolates were subjected to antimicrobial susceptibility tests, which revealed they were resistant to oxacillin, penicillin, and cefepime. Using gene sequencing, the MRS isolates were identified as S. haemolyticus, S. hominis, and S. epidermidis. Furthermore, isolates from cheese handlers' hands and artisanal unpasteurized cheese presented high genetic similarity by random amplified polymorphic DNA (RAPD-PCR) analysis, which indicates cross contamination during cheese production. Thus, we found that people directly involved in milking and cheese processing activities at small dairy farms are a potential source of contamination of MRS strains in unpasteurized milk and cheese, representing a risk to public health.

O Tempo vivido em Mrs. Dalloway à Luz da fenomenologia de Merleau-Ponty / Experienced Time in Mrs. Dalloway in Light of Merleau-Ponty's phenomenology / El Tiempo Vivido en La Señora Dalloway a la Luz de la fenomenología de Merleau-Ponty

O romance Mrs. Dalloway, escrito pela inglesa Virginia Woolf (1882-1941), é um marco na literatura universal por apresentar um novo formato na arte da escrita intitulado fluxo de consciência. Esta forma estilística visa descrever as falas e os pensamentos dos personagens por meio do discurso indireto livre, integrado à preleção do narrador. O enredo se passa em um único dia da vida da protagonista Clarissa Dalloway, no qual são captados os ínfimos detalhes do que ela experiencia. Dentre os fenômenos vivenciados encontramos a noção de tempo, por meio da qual o narrador mistura homogeneamente o fluxo passado, presente e futuro. O objetivo deste artigo é discutir a vivência do tempo na referida obra literária pautada numa discussão fenomenológica. Para isto, utilizamos como método a revisão narrativa da literatura de autores que contribuíram para o desenvolvimento da noção de tempo vivido na fenomenologia. É no fluxo do tempo que se dão os significados das experiências na história dos personagens no seu contato ambíguo com o mundo. Concluímos que as descrições elaboradas por Virginia Woolf possibilitam uma aproximação à vivência do tempo, que atravessa a totalidade da dimensão do ser...(AU)

The novel Mrs. Dalloway, written by English writer Virginia Woolf (1882-1941), is a landmark in universal literature for presenting a new format in the art of writing named Stream of Consciousness. This stylistic form aims to describe the speeches and thoughts of the characters through free indirect speech, integrated to the narrator's lecture. The novel takes place in a single day of the life of the protagonist Clarissa Dalloway, capturing the minute details of what she experiences. Among the phenomena experienced we find the notion of time, whereby the narrator mixes the past, present, and future flux into one envelope. This article thus discusses the experience of time in this literary work based on a phenomenological discussion. We conducted a review of the literature including authors that contributed to the development of the notion of experienced time in phenomenology. In the flow of time lie meanings of the experiences of characters in their ambiguous contact with the world. We conclude that the descriptions elaborated by Virginia Woolf allow for an approximation to the experience of time that crosses the totality of the dimension of being...(AU)

La novela La Señora Dalloway, de la escritora inglesa Virginia Woolf (1882-1941), es un hito en la literatura universal por presentar un nuevo formato en el arte de la escritura titulado "flujo de conciencia". Esta forma estilística pretende describir las palabras y los pensamientos de los personajes por medio del discurso indirecto libre, integrado a la prelección del narrador. La historia de la novela se pasa en un único día de la vida de la protagonista Clarissa Dalloway, en el que se captan los ínfimos detalles de lo que ella experimenta. Entre los fenómenos vivenciados encontramos la noción de tiempo, por medio de la cual el narrador mezcla el flujo pasado, presente y futuro en un envoltorio único. El objetivo de este artículo es discutir la vivencia del tiempo en la referida obra literaria pautada en una discusión fenomenológica. Para ello, utilizamos como método la revisión de la literatura de autores que contribuyeron al desarrollo de la noción de tiempo vivido en la fenomenología. Es en el flujo del tiempo que se dan los significados de las experiencias en la historia de los personajes en su contacto ambiguo con el mundo. Concluimos que las descripciones elaboradas por Virginia Woolf posibilitan una aproximación a la vivencia del tiempo, que atraviesa la totalidad de la dimensión del ser...(AU)

P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by decreased dopamine bioavailability in the substantia nigra and the striatum. Taking into account that adenosine-5'-triphosphate (ATP) and its metabolites are intensely released in the 6-hydroxydopamine (6-OHDA) animal model of PD, screening of purinergic receptor gene expression was performed. Effects of pharmacological P2Y6 or P2X7 receptor antagonism were studied in preventing or reversing hemiparkinsonian behavior and dopaminergic deficits in this animal model. P2X7 receptor antagonism with Brilliant Blue G (BBG) at a dose of 75 mg/kg re-established the dopaminergic nigrostriatal pathway in rats injured with 6-OHDA. Selective P2Y6 receptor antagonism by MRS2578 prevented dopaminergic neuron death in SH-SY5Y cells in vitro and in vivo in the substantia nigra of rats injured with 6-OHDA. Moreover, in vivo analysis showed that both treatments were accompanied by a reduction of microglial activation in the substantia nigra. Altogether, these data provide evidence that antagonism of P2X7 or P2Y6 receptors results in neuroregenerative or neuroprotective effects, respectively, possibly through modulation of neuroinflammatory responses.

Evaluación del Tratamiento Homeopático de Mujeres en Climaterio entre los 45 y 60 años con la Menopause Rating Scale (MRS) / Treatment Evaluation Homeopathic Women in Climacteric between 45 and 60 years old with Menopause Rating Scale (MRS)

La terapia hormonal es el tratamiento convencional para contrarrestar síntomas propios del climaterio; sin embargo, algunas mujeres tienen contraindicada esta terapia debido a los efectos adversos que provoca. El objetivo de este estudio fue evaluar la utilidad del tratamiento homeopático durante el climaterio con el uso de la Menopause Rating Scale (MRS) o Escala de Calificación Menopáusica. El estudio incluyó a 31 mujeres, sin problemas cardiacos, sin terapia de reemplazo hormonal y sin antecedentes de cáncer, a quienes se les aplicó el cuestionario de la MRS para obtener un puntuaje antes del tratamiento. Para determinar el tratamiento se utilizó el repertorio electrónico Radar 10.0 para Windows, con el objetivo de repertorizar los síntomas característicos de cada paciente y determinar el medicamento similar. El medicamento fue prescrito en dinamizaciones 30CH, indicando 5 gotas sublinguales cada 8 horas. La evaluación de los pacientes se llevó a cabo cada mes durante tres meses. Se realizó una evaluación final a los tres meses por comparación de puntajes de la escala inicial y final, a través de un análisis estadístico y utilizando la prueba de Wilcoxon. Lachesis trigonocephalus y Pulsatilla nigricans fueron los medicamentos indicados con mayor frecuencia, de acuerdo con los síntomas de cada paciente. La comparación del puntaje, antes y después del tratamiento, evidenció una reducción de síntomas con diferencia estadística, lo cual reflejó una mejoría global del 35%. Esta evidencia sugiere que el tratamiento homeopático beneficia a las mujeres en el climaterio. (AU)

Hormonal therapy is the conventional treatment for counteracting climacteric symptoms; however, this treatment is contraindicated in some women due to the adverse effects that this therapy may cause. The purpose of this study was to evaluate the usefulness of homeopathic therapy during the climacteric using the Menopause Rating Scale (MRS). The study included 31 women, without cardiac problems, history of no cancer or hormone replacement therapy; a MRS scale questionnaire was applied to these women to evaluate each symptom before to treatment. The Radar 10.0 for Windows electronic repertoire was used to repertorize the characteristic symptoms of each patient and determine the similarly. Homeopathic medication was prescribed in 30CH dynamization as 5 sublingual drops every 8 hrs. Patient evaluation took place monthly for 3 months. The evaluation of the results was performed by the comparison of scale scores through a statistical analysis using the Wilcoxon test. Lachesis trigonocephalus and Pulsatilla nigricans were the most frequent treatment indications, according to the symptoms of each patient. At the end of the homeopathic treatment, symptoms reduction was observed with statistical significance in the score, which reflects an overall improvement of 35%. This evidence suggested that homeopathic treatment benefits women in climacteric. (AU)

Antibacterial activity of Morinda citrifolia Linneo seeds against Methicillin-Resistant Staphylococcus spp.

In traditional medicine, Morinda citrifolia (Noni) is used to treat various ailments, including skin and respiratory-tract infections. In this work, a bio-directed study (seed extracts) with five bacteria was carried out against four clinical isolates of Methicillin-Resistant Staphylococcus (MRS) and Staphylococcus aureus ATCC 29213 strain to find molecules capable of inhibiting them. Three organic extracts were obtained by maceration of the noni seeds with ascending polarity solvents (n-hexane, dichloromethane and methanol) that were evaluated as antibacterial in the model of bioautography and broth microdilution techniques. The results showed that the methanolic extract was the most active against all bacteria (MIC = 16 mg/mL). The chromatographic fractionation performed on this extract allowed obtaining six fractions (EMF1-EMF6), of which F1, F2 and F5 exhibited activity against some of the bacteria. EMF1 fraction reached an MIC of 25 µg/mL against S. haemolyticus twice as much as the positive control, in which the chemical content is mainly composed of a mixture of γ-butyrolactones (1-2) and esterified fatty acids (3-9); chemical characterization of the nine compounds was carried out based on gas chromatography coupled to masses. EMF2 fraction, presented an MIC of 200 µg/mL against S. aureus 0198 and S. haemolyticus 562B, where a coumarin known as scopoletin (10) was isolated and active against S. aureus 0198 (MIC = 100 µg/mL). EMF5 fraction demonstrated an MIC of 200 µg/mL against S. aureus 0198, S. haemolyticus 562B and S. epidermidis 1042, in which a neolignan known as americanin A (11) was identified, showing activity against S. haemolyticus 562B and S. epidermidis 1042 (MIC = 100 µg/mL). The chemical characterization of isolated compounds 10 and 11 was performed by the analysis of 1H and 13C NMR. Therefore, the methanolic extract, identified and isolated compounds showed important antibacterial activity against the MRS, validating its use in traditional medicine.

Rates of and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: It is important to know the extent of the placebo effect in designing randomized controlled trials for patients with nonalcoholic steatohepatitis (NASH), to accurately calculate sample size and define treatment endpoints. METHODS: We performed a systematic review and meta-analysis of the placebo groups from randomized controlled trials of adults with NASH that provided histologic and/or magnetic resonance image-based assessments. We identified trials through a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus, from each database's inception through January 2, 2018. RESULTS: We identified 39 randomized controlled trials, comprising 1463 patients who received placebo. Histologic assessment data (the nonalcoholic fatty liver disease activity scores, NAS) were available from 956 patients; magnetic resonance spectroscopy data were available from 295 patients and magnetic resonance proton density fat fraction measurements from 61 patients. Overall, 25% of patients given placebo had an improvement in NAS by 2 or more points (95% CI, 21%-29%) with a small amount of heterogeneity (I2 = 27%). There were improvements by at least 1 point in steatosis scores of 33% ± 3% of patients, in hepatocyte ballooning scores of 30% ± 3% of patients, in lobular inflammation scores of 32% ± 3% of patients, and in fibrosis scores of 21% ± 3% of patients, with a moderate amount of heterogeneity among trials (I2 range, 51%-63%). Patients given placebo had a statistically significant improvement in NAS (by 0.72 ± 0.19), with a large amount of heterogeneity (I2 = 96%). Univariate and multivariate meta-regression showed that trials with a higher baseline NAS, those conducted in South America, and those in which patients had a decrease in body mass index, were associated with greater improvements in NAS among patients given placebo. Patients given placebo had significant reductions in intrahepatic triglyceride, measured by magnetic resonance spectroscopy (by 1.45% ± 0.54%) with moderate heterogeneity (I2 = 40%), and in magnetic resonance proton density fat fraction (by 2.43 ± 0.89), without heterogeneity (I2 = 0). Mean serum levels of alanine and aspartate aminotransferases decreased significantly (by 11.7 ± 3.8 U/L and 5.9 ± 2.1 U/L, respectively; P < .01 for both). CONCLUSIONS: In a meta-analysis of randomized controlled trials of NASH, patients given placebo have significant histologic, radiologic, and biochemical responses. The placebo response should be considered in designing trials of agents for treatment of NASH.

Lower Choline Rate in the Left Prefrontal Cortex Is Associated With Higher Amount of Alcohol Use in Alcohol Use Disorder.

Excessive and long-term alcohol consumption produce metabolic changes, such as of choline, in many brain regions in alcohol use disorder (AUD) and in non-AUD subjects as well. This study examined the association of choline proportion in the prefrontal cortex with pattern of alcohol use in AUD patients. The choline metabolite was acquired through a single voxel Proton Magnetic Resonance Spectroscopy (1H MRS). Between-groups comparison corrected by age showed that the ratio of Choline/Creatine (Cho/Cr) was significantly smaller (p = 0.005) in the Left Prefrontal (LPF) of AUD patients when compared to paired non-AUD subjects. A multiple regression analysis corrected by age showed that decreasing ratios of Cho/Cr in the LPF was associated with increasing amount of alcohol consumption in drinks per day (p < 0.01) in AUD patients. Rates of Cho/Cr in the LPF was inversely related to amounts of alcohol consumption possibly indicating the severity of the AUD. Thus, low proportion of Cho/Cr in the LPF could indicate more severe AUD (higher alcohol intake).