Differential proteomics of Zika virus (ZIKV) infection reveals molecular changes potentially involved in immune system evasion by a Brazilian strain of ZIKV.

Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.

Special care in dental curriculum: A transversal axis for integrating oral health with systemic health.

AIMS: Distance between dentistry and medicine is a traditional and historical obstacle that affects multiple levels of the health system, especially the health policies to improve health service quality. Changes in dental education, especially involving the adoption of integrative health models in professional development, are considered essential for reducing this gap. We aimed to show a dental curriculum focused on special care as a tool for medicine-dentistry integration. METHODS: In this study, we present a new proposal for an undergraduate dental curriculum in which topics related to special care are addressed transversally and are the core for interdisciplinary integration of oral health with systemic health. We also describe how themes related to dental home care and hospital dentistry were included in this course as basic professional competencies. RESULTS AND CONCLUSION: This initiative is aligned with the global trend to adopt educational systems that contribute to the reduction of health care inequalities and improve health service quality.

Effects of Combined Resistance Plus Aerobic Training on Body Composition, Muscle Strength, Aerobic Capacity, and Renal Function in Kidney Transplantation Subjects.

ABSTRACT: Lima, PS, de Campos, AS, de Faria Neto, O, Ferreira, TCA, Amorim, CEN, Stone, WJ, Prestes, J, Garcia, AMC, and Urtado, CB. Effects of combined resistance plus aerobic training on body composition, muscle strength, aerobic capacity, and renal function in kidney transplantation subjects. J Strength Cond Res 35(11): 3243-3250, 2021-Immunosuppression and a sedentary lifestyle may exacerbate complications such as early graft dysfunction and muscle loss, and reduce patient survival after kidney transplantation (KT). Therefore, the purpose of this study was to evaluate changes in body composition (BC), muscular strength, aerobic, and renal function in KT subjects submitted to combined resistance plus aerobic training. Twelve KT subjects were randomly assigned into groups: (G1) 12 weeks of combined training (3 males and 4 females, 54 ± 3 years); or (G2) nonexercise control (5 females, 43 ± 18 years). The subjects were evaluated for BC (dual-energy X-ray absorptiometry), estimated V̇o2peak, right-hand maximal grip strength (RHMGS) and left-hand maximal grip strength (LHMGS), and renal function. Post-training revealed that G1 reduced body fat percentage (p = 0.046), uric acid (Δ = -0.87; p = 0.023), urea (Δ = -9.43; p = 0.032), and creatinine (Δ = -0.15; p = 0.045), increased fat-free mass, estimated V̇o2peak, RHMGS, LHMGS (p < 0.05), and estimated glomerular filtration rate (eGFR) (Δ = 11.64; p = 0.017). G2 increased urea (Δ = 8.20; p = 0.017), creatinine (Δ = 0.37; p = 0.028), and decreased eGFR (Δ = -16.10; p = 0.038). After 12 weeks, urea (Δ = 24.94; p = 0.013), uric acid (Δ = 1.64; p = 0.044), and creatinine (Δ = 0.9; p = 0.011) were lower, whereas eGFR (Δ = 36.51; p = 0.009) was higher in G1. These data indicate that combined training instigates positive changes in BC, muscular strength, aerobic capacity, and renal function after KT.

Perfil epidemiológico de pacientes adultos com traumatismo cranioencefálico grave na rede SUS do Distrito Federal: um estudo retrospectivo / Epidemiological profile of adult patients with severe traumatic brain injury in the SUS network in the Federal District: a retrospective study

INTRODUÇÃO: O traumatismo cranioencefálico (TCE) é considerado uma epidemia silenciosa e um grande problema de saúde pública mundial. Dados epidemiológicos precisos podem ajudar na formulação de políticas públicas e em estratégias para reduzir a incidência do TCE. O objetivo deste estudo foi descrever a epidemiologia do TCE grave de pacientes admitidos na unidade de terapia intensiva (UTI). MÉTODOS: Trata-se de um estudo retrospectivo com coleta de dados em prontuário eletrônico na UTI de um hospital da rede SUS do Distrito Federal. Foram analisados o perfil epidemiológico e os principais desfechos clínicos e funcionais de pacientes com TCE internados entre janeiro e dezembro de 2015. Uma análise estatística descritiva foi conduzida e os dados foram expressos em médias, intervalo de confiança de 95% (IC95%) e taxas. RESULTADOS: 227 pacientes foram estudados com média de idade de 38 anos (IC95% 36 a 40), sendo 84% (191/227) do sexo masculino. O principal mecanismo de trauma foi o acidente motociclístico, 19% (43/227) seguido dos atropelamentos, 18% (40/227). O tempo médio de ventilação mecânica foi de 14 dias, (IC95% 12 a 15) e os tempos médios de internação na UTI e hospitalar foram de 16 dias, (IC95% 14 a 18) e 42 dias, (IC95% 36 a 47), respectivamente. Apenas 16% (36/227) dos pacientes conseguiu permanecer em ortostase na alta da UTI. A taxa de mortalidade na UTI foi de 25% (57/227). CONCLUSÃO: Os homens jovens são os mais acometidos por TCE grave sendo o principal mecanismo o acidente motociclístico. Estes pacientes apresentam internação hospitalar prolongada e altas taxas de mortalidade

INTRODUCTION: traumatic brain injury (TBI) has been considered a silent epidemic and a major worldwide public health problem. Accurate epidemiological data can assist in the formulation of public policies and strategies to reduce the incidence of TBI. The aim of this study was to describe the epidemiology of severe TBI in patients admitted to the intensive care unit (ICU). METHODS: this is a retrospective study with data collected from electronic medical records from the ICU of a SUS hospital in the Federal District. The epidemiological profile and the main clinical and functional outcomes of patients with TBI hospitalized between January and December 2015 were analyzed. A descriptive statistical analysis was conducted and data were expressed as averages, 95% confidence interval (95% CI) and rates. RESULTS: 227 patients were studied with a mean age of 38 (95% CI 36 to 40), 84% (191/227) being male. The main mechanism of trauma was motorcycle collision, 19% (43/227) followed by pedestrian collision, 18% (40/227). The mean time of mechanical ventilation was 14 days, (95% CI 12 to 15) and the average length of stay in the ICU and hospital was 16 days, (95% CI 14 to 18) and 42 days, (95% CI 36 to 47), respectively. Only 16% (36/227) of patients managed to remain in orthostasis upon discharge from the ICU. The mortality rate in the ICU was 25% (57/227). CONCLUSION: Young men are the most affected by severe TBI, and the main mechanism was motorcycle accidents. These patients have prolonged hospital stays and high mortality rates

Integrative proteomics and pharmacogenomics analysis of methylphenidate treatment response.

Transcriptomics and candidate gene/protein expression studies have indicated several biological processes modulated by methylphenidate (MPH), widely used in attention-deficit/hyperactivity disorder (ADHD) treatment. However, the lack of a differential proteomic profiling of MPH treatment limits the understanding of the most relevant mechanisms by which MPH exerts its pharmacological effects at the molecular level. Therefore, our aim is to investigate the MPH-induced proteomic alterations using an experimental design integrated with a pharmacogenomic analysis in a translational perspective. Proteomic analysis was performed using the cortices of Wistar-Kyoto rats, which were treated by gavage with MPH (2 mg/kg) or saline for two weeks (n = 6/group). After functional enrichment analysis of the differentially expressed proteins (DEP) in rats, the significant biological pathways were tested for association with MPH response in adults with ADHD (n = 189) using genome-wide data. Following MPH treatment in rats, 98 DEPs were found (P < 0.05 and FC < -1.0 or > 1.0). The functional enrichment analysis of the DEPs revealed 18 significant biological pathways (gene-sets) modulated by MPH, including some with recognized biological plausibility, such as those related to synaptic transmission. The pharmacogenomic analysis in the clinical sample evaluating these pathways revealed nominal associations for gene-sets related to neurotransmitter release and GABA transmission. Our results, which integrate proteomics and pharmacogenomics, revealed putative molecular effects of MPH on several biological processes, including oxidative stress, cellular respiration, and metabolism, and extended the results involving synaptic transmission pathways to a clinical sample. These findings shed light on the molecular signatures of MPH effects and possible biological sources of treatment response variability.

Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect.

Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii. Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.

Gremlin-1 potentiates the dedifferentiation of VSMC in early stages of atherosclerosis.

Vascular smooth muscle cells (VSMC) are highly specialized, and exhibit a contractile phenotype when mature and fully differentiated, being responsible for vessel homeostasis and blood pressure control. In response to pro-atherogenic stimuli VSMC alter their state of differentiation, increase proliferation and migration, resulting in SMC phenotypes ranging from contractile to synthetic. This variability is observed in cell morphology and expression level of marker genes for differentiation status. There is growing evidence that bone morphogenetic protein (BMP) signaling is involved in vascular diseases, including atherosclerosis. Here, we evaluated in vitro the role of specific agonists/antagonists belonging to the BMP pathway on dedifferentiation of VSMC harvested during early stages of atherosclerosis. RESULTS: Comparing primary VSMC isolated from aortas of susceptible ApoE-/- animals fed 8 weeks of western diet with their littermate controls fed usual diet, we observed that recombinant BMP4 was able to reduce SM22-alpha and alpha actin gene expression indicating dedifferentiation was under way. Unexpectedly, treatment with recombinant Gremlin-1, a known BMP antagonist, also reduced 4-6.5 folds gene expression of SM22-alpha, alpha-actin and, calponin, exclusively in VSMC from ApoE-/- animals, independently on the diet consumed. CONCLUSION: Our data show that BMP4 is capable of modulating of SM22-alpha and alpha actin gene expression, indicative of cell dedifferentiation in VSMC. Additionally, we report for first time that Gremlin-1 acts independently of the BMP pathway and selectively on VSMC from susceptible animals, reducing the expression of all genes evaluated.

Proteome profiling of triple negative breast cancer cells overexpressing NOD1 and NOD2 receptors unveils molecular signatures of malignant cell proliferation.

BACKGROUND: Triple negative breast cancer (TNBC) is a malignancy with very poor prognosis, due to its aggressive clinical characteristics and lack of response to receptor-targeted drug therapy. In TNBC, immune-related pathways are typically upregulated and may be associated with a better prognosis of the disease, encouraging the pursuit for immunotherapeutic options. A number of immune-related molecules have already been associated to the onset and progression of breast cancer, including NOD1 and NOD2, innate immune receptors of bacterial-derived components which activate pro-inflammatory and survival pathways. In the context of TNBC, overexpression of either NOD1or NOD2 is shown to reduce cell proliferation and increase clonogenic potential in vitro. To further investigate the pathways linking NOD1 and NOD2 signaling to tumorigenesis in TNBC, we undertook a global proteome profiling of TNBC-derived cells ectopically expressing each one of these NOD receptors. RESULTS: We have identified a total of 95 and 58 differentially regulated proteins in NOD1- and NOD2-overexpressing cells, respectively. We used bioinformatics analyses to identify enriched molecular signatures aiming to integrate the differentially regulated proteins into functional networks. These analyses suggest that overexpression of both NOD1 and NOD2 may disrupt immune-related pathways, particularly NF-κB and MAPK signaling cascades. Moreover, overexpression of either of these receptors may affect several stress response and protein degradation systems, such as autophagy and the ubiquitin-proteasome complex. Interestingly, the levels of several proteins associated to cellular adhesion and migration were also affected in these NOD-overexpressing cells. CONCLUSIONS: Our proteomic analyses shed new light on the molecular pathways that may be modulating tumorigenesis via NOD1 and NOD2 signaling in TNBC. Up- and downregulation of several proteins associated to inflammation and stress response pathways may promote activation of protein degradation systems, as well as modulate cell-cycle and cellular adhesion proteins. Altogether, these signals seem to be modulating cellular proliferation and migration via NF-κB, PI3K/Akt/mTOR and MAPK signaling pathways. Further investigation of altered proteins in these pathways may provide more insights on relevant targets, possibly enabling the immunomodulation of tumorigenesis in the aggressive TNBC phenotype.

Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases.

The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer's disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson's disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire. INTERVENTION: Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. OUTCOMES: (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. RESULTS: There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. CONCLUSIONS: CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

First experience with multiple mini interview for medical school admission in Brazil: Does it work in a different cultural scenario?

PURPOSE: Evaluation of non-cognitive skills never has been used in Brazil. This study aims to evaluate Multiple Mini Interviews (MMI) in the admission process of a School of Medicine in São Paulo, Brazil. METHODS: The population of the study comprised 240 applicants summoned for the interviews, and 96 raters. MMI contributed to 25% of the applicants' final grade. Eight scenarios were created with the aim of evaluating different non-cognitive skills, each one had two raters. At the end of the interviews, the applicants and raters described their impressions about MMI. The reliability of the MMI was analyzed using the Theory of Generalization and Many-Facet Rasch Model (MFRM). RESULTS: The G-study showed that the general reliability of the process was satisfactory (coefficient G = 0.743). The MMI grades were not affected by the raters' profile, time of interview (p = 0.715), and randomization group (p = 0.353). The Rasch analysis showed that there was no misfitting effects or inconsistent stations or raters. A significant majority of the applicants (98%) and all the raters believed MMIs were important in selecting students with a more adequate profile to study medicine. CONCLUSIONS: The general reliability of the selection process was excellent, and it was fully accepted by the applicants and raters.

Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-ß1-Induced Apoptosis.

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of men and women of all ages and racial groups. Loss of mesangial cells (MC) represents an early common feature in the pathogenesis of CKD. Transforming growth factor-ß1 (TGF-ß1) is a key inducer of kidney damage and triggers several pathological changes in renal cells, notably MC apoptosis. However, the mechanism of MC apoptosis induced by TGF-ß1 remains elusive. Here, we demonstrate for the first time a novel regulatory pathway in which the disheveled-binding antagonist of ß-catenin 1 (Dact1) gene is upregulated by TGF-ß1, inducing MC apoptosis. We also show that the inhibitory effect of Dact1 and TGF-ß1 on the transcriptional activation of the pro-survival Wnt pathway is the mechanism of death induction. In addition, Dact1 mRNA/protein levels are increased in kidney remnants from 5/6 nephrectomized rats and strongly correlate with TGF-ß1 expression. Together, our results point to Dact1 as a novel element controlling MC survival that is causally related to CKD progression. J. Cell. Physiol. 232: 2104-2111, 2017. © 2016 Wiley Periodicals, Inc.

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals.

OBJECTIVE:: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. METHODS:: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. RESULTS:: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). CONCLUSION:: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others. OBJETIVO:: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. MÉTODOS:: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. RESULTADOS:: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). CONCLUSÃO:: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals / Imagem molecular pré-clínica: desenvolvimento de instrumentação para pesquisa translacional com pequenos animais

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

RESUMO Objetivo: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Métodos: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Resultados: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Conclusão: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Low back pain / Lombociatalgia

ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain is present in 37 to 55% of cases of low back pain. Neuropathic pain is associated with more intense pain, more severe comorbidities and worse quality of life. In addition, costs are 67% higher when compared to other etiologies. The purpose of this article is to review this issue that has significant impact on quality of life. CONTENTS: Pain radiating to the lower limb may be radicular or referred pain. Radiation paths of lumbar roots and myofascial trigger points may be very similar, as the root of L5 and gluteus minimus trigger point. Thus, it is essential to use a tool for neuropathic pain assessment, such as: Douleur neuropathique 4 questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale e painDETECT. Clinical history and physical evaluation should formulate diagnostic hypotheses, which should be confirmed with complementary tests when necessary. Guidelines for the treatment of neuropathic pain consider as the first line drugs: anticonvulsants (gabapentin and pregabalin), tricyclic antidepressants (amitriptyline, imipramine, clomipramine and nortriptyline), selective serotonin and norepinephrine reuptake inhibitor (duloxetine and venlafaxine). Second line drugs are: 5% lidocaine patches in localized neuropathic pain and opioids. Surgical treatment of lumbar radiculopathy should be indicated when there is limited or low efficacy of multimodal conservative treatment. CONCLUSION: In low back pain, diagnosis of neuropathic component is critical. Multimodal treatment is imperative, as well as other strategies to rehabilitate and improve the patient's quality of life.

RESUMO JUSTIFICATIVA E OBJETIVOS A dor neuropática está presente em 37 a 55% dos casos de lombociatalgia, a dor neuropática está relacionada com dor mais intensa, comorbidades mais graves e piora da qualidade de vida. Além disso, os custos são 67% maiores quando comparada a outras etiologias. O objetivo deste artigo foi fazer uma revisão sobre este tema que causa impacto importante na qualidade de vida dos pacientes. CONTEÚDO A dor irradiada para o membro inferior pode ser de origem radicular ou referida. Os trajetos de irradiação para o membro inferior de raízes lombares e de pontos-gatilhos miofasciais podem ser muito parecidos, como a raiz L5 e ponto-gatilho do glúteo mínimo. Assim, é essencial a utilização de um instrumento para avaliação da dor neuropática, como: Douleur neuropathique 4 questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale e Pain DETECT. Os dados da anamnese e do exame físico devem formular hipóteses diagnósticas, que devem ser confirmadas com os exames complementares quando necessário. As diretrizes para o tratamento da dor neuropática consideram como primeira linha: anticonvulsivantes (gabapentina e pregabalina), antidepressivos tricíclicos (amitriptilina, imipramina, clomipramina e nortriptilina), inibidores seletivos da receptação de serotonina e de noradrenalina (duloxetina e venlafaxina). As medicações de segunda linha são: emplastros de lidocaína a 5% em dor neuropática localizada e os opioides. O tratamento cirúrgico da radiculopatia lombar deve ser indicado quando existir limitação ou baixa eficácia no tratamento conservador multimodal. CONCLUSÃO Na lombalgia o diagnóstico do componente neuropático é fundamental. O tratamento multimodal é imperativo, assim como outras estratégias para reabilitar e melhorar a qualidade de vida do paciente.

Agreement on the prescription of antimicrobial drugs.

BACKGROUND: There is universal awareness of the difficulties faced by doctors when prescribing antimicrobials. METHODS: Over a six-month period patients hospitalized in the ICU and under treatment with antibiotics and/or antifungals were eligible to participate in the study. The data were assessed by two infectious diseases specialists. Once completed, all case forms were sent independently to both evaluators (TZSC and ARM) by e-mail. Based on the data received, the evaluator completed a form automatically generated on the e-mail and returned it to the original mailbox for further analysis. We assessed the level of agreement between infectious disease specialists and the physicians directly responsible for the decision to begin antimicrobial therapy, as well as to assess the appropriateness of the regimen prescribed. RESULTS: Among the antimicrobial regimens prescribed to the 177 patients, 36% were considered inappropriate by specialist #1 and 38% were considered inappropriate by specialist #2. We found 78% agreement by at least one of the infectious disease specialists with the prescribed antimicrobial regimen, and in 49% of cases both specialists agreed with the prescribed regimen. Both disagreed with the prescribed regimen in 22% of the cases and they disagreed between themselves in 29% of the cases. CONCLUSION: This study highlights the difficulties in prescribing effective empirical antimicrobial therapy--they are of such magnitude that even two specialists in infectious diseases, well acquainted with our hospital's resistance patterns and our patients' profiles have considerable disagreement.

TBX3, a downstream target of TGF-ß1, inhibits mesangial cell apoptosis.

Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-ß1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-ß1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14(ARF)-Mdm2-p53 pathway, while TBX3+2α role has not been defined. We demonstrated that TBX3 overexpression abrogated MC apoptosis induced by serum deprivation. Moreover, we observed an enhancement in TBX3 protein expression both in glomerular and tubular regions in the model of 5/6 nephrectomy, temporally related to increased expression of TGF-ß1, type IV collagen and fibronectin. Our results indicate that TBX3 acts as an anti-apoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-ß1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies.

Preterm children have unfavorable motor, cognitive, and functional performance when compared to term children of preschool age / Crianças pré-termo apresentam desempenho motor, cognitivo e funcional desfavorável em relação a neonatos a termo em idade pré-escolar

OBJECTIVE: to compare the motor coordination, cognitive, and functional development of preterm and term children at the age of 4 years. METHODS: this was a cross-sectional study of 124 four-year-old children, distributed in two different groups, according to gestational age and birth weight, paired by gender, age, and socioeconomic level. All children were evaluated by the Movement Assessment Battery for Children - second edition (MABC-2), the Pediatric Evaluation of Disability Inventory (PEDI), and the Columbia Mental Maturity Scale (CMMS). RESULTS: preterm children had worse performance in all tests, and 29.1% of the preterm and 6.5% of term groups had scores on the MABC-2 indicative of motor coordination disorder (p = 0.002). In the CMMS (p = 0.034), the median of the standardized score for the preterm group was 99.0 (± 13.75) and 103.0 (± 12.25) for the term group; on the PEDI, preterm children showed more limited skill repertoire (p = 0.001) and required more assistance from the caregiver (p = 0.010) than term children. CONCLUSION: this study reinforced the evidence that preterm children from different socioeconomic backgrounds are more likely to have motor, cognitive, and functional development impairment, detectable before school age, than their term peers. .

OBJETIVO: comparar o desenvolvimento da coordenação motora, o desenvolvimento cognitivo e o desempenho funcional de crianças nascidas pré-termo e a termo, aos quatro anos de idade. MÉTODOS: estudo transversal com 124 crianças de quatro anos de idade, distribuídas em dois grupos distintos, de acordo com a idade gestacional e peso ao nascimento, pareadas com relação ao sexo, idade e nível socioeconômico. Todas as crianças foram avaliadas pelos testes Movement Assessment Battery for Children - Second Edition (MABC-2), Inventário de Avaliação Pediátrica de Incapacidade (PEDI) e Escala de Maturidade Mental Colúmbia (EMMC). RESULTADOS: as crianças pré-termo tiveram pior desempenho em todos os testes, sendo que 29,1% das crianças do grupo pré-termo e 6,5% do grupo a termo apresentaram pontuação no MABC-2 indicativa de sinais de transtorno da coordenação motora (p = 0,002). No Columbia (p = 0,034), a mediana do resultado padronizado para o grupo pré-termo foi de 99,0 (±13,75), e do grupo a termo foi 103,0 (±12,25); no PEDI, crianças pré-termo tiveram menor repertório de habilidades (p = 0,001) e necessitaram de maior assistência do cuidador (p = 0,010) do que as crianças a termo. CONCLUSÃO: este estudo reforça as evidências de que crianças pré-termo, de diferentes níveis socioeconômicos, são mais propensas a apresentarem alterações no desenvolvimento motor, cognitivo e funcional, detectáveis antes da idade escolar, que seus pares nascidos a termo. .

Preterm children have unfavorable motor, cognitive, and functional performance when compared to term children of preschool age.

OBJECTIVE: to compare the motor coordination, cognitive, and functional development of preterm and term children at the age of 4 years. METHODS: this was a cross-sectional study of 124 four-year-old children, distributed in two different groups, according to gestational age and birth weight, paired by gender, age, and socioeconomic level. All children were evaluated by the Movement Assessment Battery for Children - second edition (MABC-2), the Pediatric Evaluation of Disability Inventory (PEDI), and the Columbia Mental Maturity Scale (CMMS). RESULTS: preterm children had worse performance in all tests, and 29.1% of the preterm and 6.5% of term groups had scores on the MABC-2 indicative of motor coordination disorder (p=0.002). In the CMMS (p=0.034), the median of the standardized score for the preterm group was 99.0 (± 13.75) and 103.0 (± 12.25) for the term group; on the PEDI, preterm children showed more limited skill repertoire (p=0.001) and required more assistance from the caregiver (p=0.010) than term children. CONCLUSION: this study reinforced the evidence that preterm children from different socioeconomic backgrounds are more likely to have motor, cognitive, and functional development impairment, detectable before school age, than their term peers.

Assessment of motor coordination and dexterity of six years old children: A psychometric analysis / Avaliação da coordenação e destreza motora de crianças de seis anos: Análise psicométrica / Evaluación de la coordinación motora y la destreza de los niños de seis años de edad: Un análisis psicométrica

Motor coordination of six-year-old children was examined using the Assessment of Motor Coordination and Dexterity, AMCD (Avaliação da Coordenação e Destreza Motora - ACOORDEM), in order to verify test-retest reliability and investigate whether motor performance is influenced by gender, type of school and residence location. Eighty-five children were evaluated, and their parents and teachers completed questionnaires. For test-retest reliability, the AMCD was repeated with 10 children. Mann-Whitney and chi-square tests identified significant influence of sex, type of school and residence location in just a few of the test items. The test-retest reliability was moderate in the items performance, and good to excellent in the majority of the questionnaires' items. We conclude that some items should be revised and normative tables for the identification of motor delay could be created considering only the age variable. Future studies should continue the process of validating the AMCD instrument with the assessment of younger children...

A coordenação motora de crianças de seis anos foi examinada através do teste de Avaliação da Coordenação e Destreza Motora, ACOORDEM (em desenvolvimento) com objetivo de avaliar a confiabilidade teste-reteste e investigar se o desempenho motor é influenciado pelo sexo, tipo de escola e local de moradia. Foram avaliadas 85 crianças e seus pais e professores responderam questionários. Para detectar a confiabilidade teste-reteste, a ACOORDEM foi reaplicada em 10 crianças. Testes de Mann-Whitney e Qui-quadrado identificaram influência significativa do sexo, tipo de escola e local de moradia em apenas alguns itens. A confiabilidade teste-reteste foi moderada para os itens de desempenho, e de boa a excelente para maioria dos itens dos questionários. Conclui-se que alguns itens devem ser revisados e tabelas normativas de desempenho para identificação de atraso motor podem ser criadas considerando apenas a variável idade. Estudos futuros devem dar continuidade ao processo de criação do instrumento com avaliação de crianças mais jovens...

La coordinación motora en desarrollo del niños de seis años fue examinada por la Evaluación de la coordinación y destreza motora (Avaliação da Coordenação e Destreza Motora - ACOORDEM) con objetivo de evaluar la confiabilidad prueba-reprueba e investigar si el desempeño motor es influenciado por el sexo, tipo de escuela y sitio de la morada. Fueron evaluados 85 niños y sus padres y profesores respondieron cuestionarios. Para confiabilidad prueba- reprueba, la ACOORDEM fue aplicada de nuevo en 10 niños. Pruebas de Mann-Whitney y Chi-cuadrado identificaron significativa influencia del sexo, tipo de escuela y sitio de morada solo en algunos ítems. La confiabilidad prueba-reprueba fue moderada para los ítems de desempeño y de buena a excelente para la mayoría de los ítems del los cuestionarios. Se concluye que algunos ítems deben ser revisados y tablas normativas de desempeño para la identificación del atraso motor pueden ser creadas considerando solo la variable edad. Estudios futuros deben dar continuad al proceso de creación del instrumento con evaluación de niños más jóvenes...