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Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing.Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM.Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P0.0001).Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Made available in DSpace on 2020-12-12T02:00:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 BACKGROUND: Teachers perform repetitive movements all day, which can cause pain in body regions. This article analyzes the association of pain with sleep quality in this population. OBJECTIVE: The objective of the study was to analyze the relationship of musculoskeletal pain and sleep quality in teachers from public schools. METHODS: The sample consisted of 242 teachers, selected in a random process. Musculoskeletal pain and sleep quality were evaluated by using a questionnaire. The association between sleep quality and musculoskeletal pain was evaluated using the chi-square test. The magnitude of the associations was verified by Binary Logistic Regression, adjusted by sex, age, BMI, and socioeconomic status. RESULTS: Teachers with poor sleep quality presented higher body mass index (BMI) values when compared to teachers with good sleep quality (27.9 vs 26.0, p = 0.012). Teachers with poor sleep quality were approximately twice as likely to report thoracic pain (OR = 2.16[95% CI = 1.12-4.16]), wrist pain (OR = 3.28[95% CI = 1.18-9.07]), low back pain (OR = 3.09[95% CI = 1.29-7.41]), and ankle/foot pain (OR = 2.83[95% CI = 1.32-6.08]). CONCLUSIONS: Teachers with poor sleep quality were approximately twice as likely to present pain in several body parts. Our findings revealed that poor sleep quality was significantly associated with musculoskeletal pain in Brazilian teachers of public schools, regardless of confounding factors. São Paulo State University (Unesp) School of Technology and Sciences Presidente Prudente Department of Physical Therapy Universidade Federal de Minas Gerais (UFMG) São Paulo State University (Unesp) School of Technology and Sciences Presidente Prudente

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). Patients and methods VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and 1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. Results Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. Conclusions BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy, This work was supported by Roche Farma S.A (no grant number). Medical writing support was funded by Roche Farma S.A and provided by H. Lamb and L. Miller of Miller Medical Communications Ltd.

INTRODUCTION: Levels of neuro-filament light chain (NFL) correlate with clinical and radiological activity in multiple sclerosis (MS) and have been used as a surrogate biomarker of axonal destruction related to inflammatory activity. The main objective of this work is to explore the specific contribution of acute inflammation within the spinal cord to the elevation of NFL levels. PATIENTS AND METHODS: MS patients with a baseline study of NFL at diagnosis of the disease and a brain and spinal cord MRI scan were selected. Patients were classified according to the presence, number and location of gadolinium enhancing lesion (GEL) and the relationship between NFL levels and both brain and spinal cord GEL were explored. RESULTS: Seventy-seven patients were selected. NFL levels were significantly higher in patients with only one GEL restricted to the brain than those without GEL (1702 pg/ml vs 722.7 pg/mL, p = 0.03) and correlated with number. However, no differences were seen among patients with GEL limited to the spinal cord and those without GEL (735.2 pg/ml vs 722.7 pg/mL). CONCLUSION: Our study reaffirms the value of NFL levels in monitoring asymptomatic inflammatory activity in the brain measured by GEL. However, NFL concentration is not as useful when only inflammatory activity occurs in the spinal cord.

This study aimed to analyze the association between body dissatisfaction and sports participation from childhood to adolescence in a school-based sample of adolescents, according to sex.A total of 1011 adolescents of 13.1 ± 2.3 years of age were evaluated. Body dissatisfaction was assessed by the Silhouettes Scale and sports participation for at least one consecutive year was retrospectively assessed by closed specific questions related to childhood and adolescence periods. Body mass index (BMI) and abdominal obesity were objectively measured. Habitual practice of physical activity (PA), socioeconomic status (SES), and ethnicity were assessed through questionnaires.Sports participation from childhood to adolescence was observed in 55.1% of boys and in 41.2% of girls. Boys with body dissatisfaction showed lower habitual PA in leisure time (Baecke score = 4.38 ± 2.27 vs. 5.15 ± 2.25, p 0.05) and in total (Baecke score = 9.34 ± 2.64 vs. 9.96 ± 2.68, p 0.05) than those who were satisfied. No differences were observed among girls. Sports participation from childhood to adolescence was associated with 42% less chance of having body dissatisfaction in boys (OR = 0.58 [95%CI = 0.36-0.94]). No significant association was observed among girls.Sports participation from childhood to adolescence was negatively associated with body dissatisfaction in boys. The continuity of physical activity during youth may be an important modifiable factor to reduce body dissatisfaction.

Classically the results of any joint replacement surgery are evaluated at a minimum of 5 years. This period could be considered excessive to evaluate the functional results of this procedure. The objective of this study is to compare functional and quality of life results to 1 and five years of follow-up following a total knee replacement (TKR).Prospective observational study. All patients visited one year after the implantation of TKR were included. All of these filled out the SF-36 questionnaire and the KSS valuation scale. Both were administered again at age five after surgery.689 patients were initially included in the study (163 men [23.7%] and 526 women [76.3%]) with an average age of 72.2 years. At age 5,585 (84.9%) of these patients were re-analyzed. While the knee section of the KSS scale remained similar in these two periods, the function section of the KSS titration scale showed a slight worsening over time (p = 0.008). With respect to SF-36, the physical summation worsened at five years (p = 0.00) and the mental summation remained stable (n.s.) between the year and five years after surgery.Five years after a TKR, the physical exam does not vary from the year of surgery. However, the subjective evaluation measured by the function-KSS section and the physical SF-36, worsen slightly during this period. This could be due to aging patients.Clásicamente los resultados de cualquier cirugía de reemplazo articular se evalúan en un mínimo de cinco años. Este período podría considerarse excesivo para evaluar los resultados funcionales de este procedimiento. El objetivo de este estudio es comparar los resultados funcionales y de calidad de vida a uno y cinco años de seguimiento tras una artroplastía total de rodilla (ATR).Estudio prospectivo observacional. Se incluyeron todos aquellos pacientes visitados un año después de la implantación de una ATR. Todos ellos rellenaron el cuestionario SF-36 y la escala de valoración KSS. Ambos fueron administrados nuevamente al cabo de cinco años de la cirugía.689 pacientes fueron incluidos inicialmente en el estudio (163 hombres [23.7%] y 526 mujeres [76.3%]) con una edad media de 72.2 años. A los cinco años, 585 (84.9%) de estos pacientes fueron analizados de nuevo. Mientras que la sección rodilla de la escala KSS se mantenía similar en estos dos períodos, la sección función de la escala de valoración KSS mostraba un leve empeoramiento con el tiempo (p = 0.008). Con respecto al SF-36, el sumatorio físico empeoraba a los cinco años (p = 0.00) y el sumatorio mental se mantenía estable (n.s.) entre un año y cinco años tras la cirugía.Después de cinco años de una ATR, el examen físico no varía con respecto al año de la cirugía. Sin embargo, la evaluación subjetiva medida mediante la sección función-KSS y el SF-36 físico empeoran ligeramente durante este período. Esto podría ser debido al envejecimiento de los pacientes.

Made available in DSpace on 2021-06-25T10:10:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 This study analyzed the relationship between sedentary behavior and cardiovascular parameters in normal weight and overweight adolescents. The sample included 449 boys and 555 girls with mean age of 13 years from public schools, which were divided into five geographical regions, with data collections performed in one selected school from each region. Sedentary behavior was assessed by screen time on TV, computer, videogame and cell phone/tablet, with good reliability in adolescents. Physical activity was assessed by Baecke’s questionnaire, validated for adolescents. Measures of body weight, height and waist circumference were collected. Adolescents were classified as overweight or normal weight by cut-off points of body mass index for age and sex. Cardiovascular parameters were evaluated by oscillometric device and heart rate by specific monitor. Computer use was positively related to systolic blood pressure (SBP) (β = 0.35; 95%CI = 0.07–0.62) and diastolic blood pressure (DBP) (β = 0.25; 95%CI = 0.05–0.44) in normal weight but not in overweight adolescents. Similar results were observed for cell phone/tablet in SBP (β = 0.46; 95%CI = 0.20–0.72) and DBP (β = 0.36; 95%CI = 0.18–0.54), only for normal weight. The cluster of screen time was related to SBP in normal weight (β = 0.44; 95%CI = 0.03–0.84) and overweight (β = 0.60; 95%CI = 0.01–1.19). Screen time in computer and cell phone/tablet was more related to cardiovascular parameters in normal weight than overweight adolescents. Movement Sciences Post Graduation Program—Sao Paulo State University (Unesp) School of Technology and Sciences Department of Physical Education, Roberto Simonsen Street, Number 305 Rehabilitation Sciences Post Graduation Program Universidade Nove de Julho Department of Physical Education, Vergueiro Street, Number 235-249 Physiotherapy Post Graduation Program Sao Paulo State University (Unesp) School of Technology and Sciences Department of Physiotherapy, Roberto Simonsen Street, Number 305 Movement Sciences Post Graduation Program—Sao Paulo State University (Unesp) School of Technology and Sciences Department of Physical Education, Roberto Simonsen Street, Number 305 Physiotherapy Post Graduation Program Sao Paulo State University (Unesp) School of Technology and Sciences Department of Physiotherapy, Roberto Simonsen Street, Number 305

Made available in DSpace on 2020-12-10T20:06:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-27 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This study analyzed the association of body size dissatisfaction with body mass index, dietary pattern, and physical activity in adolescents. A sample of 1074 participants between 10 and 17 years of age was recruited. Body size dissatisfaction was assessed with the silhouettes' scale. Dietary pattern, physical activity, and socioeconomic status were assessed with questionnaires. Body mass index was measured objectively. The prevalence of body size dissatisfaction was 77.0%, where 29.8% desired to increase body size and 47.2% desired to decrease body size. Adolescents who desired to increase body size were more likely to consume vegetables and sweets and less likely to be in the highest quartile of physical activity than satisfied adolescents. Adolescents who desired to reduce body size were more likely to report lower fruit and vegetable consumption than satisfied adolescents. Health actions aiming to reduce body dissatisfaction in adolescents should address improvement in dietary pattern and physical activity engagement, considering that desires to increase or decrease body size were differently associated in this study. Sao Paulo State Univ, Movement Sci Postgrad Program, Presidente Prudente, Brazil Sao Paulo State Univ, Physiotherapy Postgrad Program, Presidente Prudente, Brazil Sao Paulo State Univ, Movement Sci Postgrad Program, Presidente Prudente, Brazil Sao Paulo State Univ, Physiotherapy Postgrad Program, Presidente Prudente, Brazil CAPES: 001

Background Family process disruption is one of the main consequences of the hospitalization of a critically ill child in a Paediatric Intensive Care Unit (PICU). Children’s visits to PICU may help improve family coping. However, this is not standard practice and nurses’ experiences in facilitating children’s visits to units where it is encouraged is unknown. Aim To explore nurses’ experience related to promoting the visits of siblings to PICU. Methods An interpretative phenomenological study was carried out through in-depth interviews in two PICUs belonging to third level public hospitals in Madrid. Twelve nurses with more than two years of experience in PICU were interviewed. They were all were working in PICU during the study. Furthermore, a PICU psychologist with an experience of four years was interviewed and this was considered shadowed data. Data analysis followed a thematic discourse analysis. Results Nurses’ experience of facilitating children’s visits to PICU can be condensed into four themes: emerging demand for visits, progressive preparation, decision-making through common consensus and creating intimate spaces. Conclusions The experience of nurses in facilitating visits is mainly in response to the demand of families going through prolonged hospitalisation or end-of-life situations. The role of the nurse is one of accompaniment, recognising the major role of parents in the preparation of children and in developing the visit. Nurses feel insecure and lack resources for emotional support and demand action protocols to guide intervention and decision making.

This prospective, randomised, controlled clinical trial evaluated the relationship between alveolar ridge dimensional change and recession with the implant position (horizontal and vertical) and tissue phenotype in immediately placed and provisionalised implants without the use of bone grafting.Patients (n = 40) with a hopeless maxillary anterior tooth received an immediate implant and immediate provisional or customised healing abutment after flapless extraction. Implants were finally restored 3 months after placement and followed up for 6 months after delivery of the restoration. The alveolar ridge dimensional change and recession were measured using cone beam computed tomography (CBCT) scans and digitalised dental casts. Alveolar contour changes were correlated to implant position and tissue phenotype.The tissue phenotype showed no significant correlation to the alveolar ridge dimensional change. At 6 months, the average alveolar ridge dimensional change was approximately 0.7 mm in the buccolingual dimension independent of tissue phenotype. A statistically significant difference was observed on the recession values comparing tissue phenotypes, with more recession observed in the thin phenotype (1.96 mm) than in the thick phenotype (1.18 mm). A significant correlation was observed between horizontal implant position and buccolingual alveolar ridge change. A positive correlation was observed between the horizontal implant position and the dimensional change measured in the casts at the level of the free gingival margin. A statistically significant negative correlation was observed between the horizontal implant position and the resorption measured by the CBCT scans.Patients with thin tissue phenotype had a more marked recession. The horizontal implant position showed a relationship to the alveolar ridge dimensional changes observed. The greater the buccal gap distance between the implant and the buccal plate, the lesser the radiographic changes observed in the alveolar bone, however, the greater the changes observed in the buccal aspect of the casts at the level of the free gingival margin.

Supplemental Digital Content is available in the text, Introduction: Cardiac autonomic modulation is an important marker of cardiovascular health and the practice of physical activity is a fundamental tool for good maintenance or increments in this marker. However, it is not clear in the literature whether different intensities and different domains of physical activity are related in the same way to cardiac autonomic modulation. Objectives: This randomized epidemiologic study will examine the relationship between cardiac autonomic modulation and different intensities and domains of physical activity in a representative sample of adults. Methods: The sample of study will consist of 252 subjects aged from 18 years and above. The sample will be randomized through census sectors in which the neighborhoods, streets, and houses will also be randomized. Cardiac autonomic modulation will be assessed by heart rate variability and the intensity (mild, moderate, intense) of physical activity will be evaluated by means of accelerometers, while the different domains of physical activity (physical activity at work, occupational activities) will be evaluated through a questionnaire. The relationship between cardiac autonomic modulation and different physical activity intensities, as well as the different domains will be analyzed by linear regression, considering a statistical significance of 5% and a 95% confidence interval. This research protocol is registered in ClinicalTrials.gov at number NCT03986879.

Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes.A cross-sectional design with data from 396 children (age 5 to 17 years) was analyzed with a generalized linear model to find the coefficients for triglycerides, high-density-lipoprotein cholesterol, and waist circumference-body mass index quotient. The model was constructed according to sex and age and designated PMI. A cross-validation analysis was performed and a receiver operating characteristic curve was used to determine cut-off points.Significant moderate correlation was found between PMI and homeostatic model assessment of insulin resistance (HOMA-IR) ( r = 0.452; P = .003), Matsuda ( r = -0.366; P = .019), alanine aminotransferase ( r = 0.315, P = .045), and γ-glutamyltransferase ( r = 0.397; P = .010). A PMI score1.7 was considered as risk.PMI correlates with HOMA-IR, Matsuda, and hepatic enzymes. It could be helpful for identifying children at risk for cardiometabolic diseases.ALT = alanine transaminase BMI = body mass index GGT = γ-glutamyltransferase HDL-C = high-density-lipoprotein cholesterol HOMA-IR = homeostatic model assessment of insulin resistance hs-CRP = high sensitivity C-reactive protein ISI = insulin sensitivity index NAFLD = nonalcoholic fatty liver disease PMI = pediatric metabolic index QUICKI = quantitative insulin sensitivity check index ROC = receiver operating characteristic TG = triglyceride TNF-α = tumor necrosis factor-alpha VAI = visceral adiposity index VAT = visceral adipose tissue WC = waist circumference.

Background Pulse pressure variation (PPV) is widely used as a predictor of fluid responsiveness. However, a previous study has suggested a ‘grey zone' between 9 and 13% in which PPV would be inconclusive to predict fluid responsiveness. Considering PPV is based on cardiopulmonary interactions, we evaluated whether an augmented PPV using a temporary increase in tidal volume (VT) from 8 to 12 ml kg−1 has the predictability for fluid responsiveness in patients within the grey zone. Methods Adult patients requiring general anaesthesia were enrolled. During the period when PPV was within the range of 9–13%, haemodynamic variables such as stroke volume index (SVI) and PPV with an 8 ml kg−1 tidal volume ventilation (PPV8) were obtained before and after volume expansion (6 ml kg−1) under mechanical ventilation. Augmented PPV induced by 2-min ventilation with a VT of 12 ml kg−1 (PPV12) was also recorded immediately before volume loading. The patients whose SVI increased ≥10% after volume expansion were considered responders. Results In 38 enrolled patients, 20 were responders. Receiver operating characteristic curve analysis showed PPV12 had an excellent predictability for fluid responsiveness {area under the curve [AUC]=0.935 [95% confidence interval (CI) 0.805–0.989]; sensitivity 95%; specificity 72%; P 17%. However, PPV8 failed to show significant predictability [AUC=0.668 (95% CI 0.497–0.812); sensitivity 65%; specificity 61%; P=0.06]. Conclusion In mechanically ventilated patients, our augmented PPV successfully predicted fluid responsiveness in the previously suggested grey zone. Clinical trial registration ClinicalTrials.gov, NCT02653469.

Made available in DSpace on 2020-12-10T20:01:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01. Added 1 bitstream(s) on 2021-07-15T14:37:21Z : No. of bitstreams: 1 S0034-89102020000100241.pdf: 241662 bytes, checksum: c2ff3561d8192c5f3a9242e971dac6a2 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) OBJECTIVE: To analyze the association of television food advertisements with eating habits in Brazilian adolescents. METHODS: The sample was composed of 1,011 adolescents, aged from 10-17 years. The influence of television food advertisements on eating habits, as well as food consumption and socioeconomic variables were assessed through questionnaires. A binary logistic regression was performed to assess the magnitude of the associations, adjusted for gender, age, socioeconomic status, and parental schooling. RESULTS: Of the sample, 83.3% (n = 843) reported food consumption while watching TV. Adolescents who do not consume food while watching TV had a higher weekly consumption of fruits (3.98, SD = 2.0 versus 3.39, SD = 2.1) and vegetables (4.1, SD = 2.2 versus 3.4, SD = 2.3). Adolescents that consume food while watching TV had higher weekly consumption of fried foods (3.1, SD = 2.0 versus 2.3, SD = 1.7), sweets (4.1, SD = 2.1 versus 3.3, SD = 2.1), soft drinks (3.2, SD = 2.1 versus 2.2, SD = 1.9), and snacks (2.3, SD = 2.0 versus 1.6, SD = 1.7). For 73,8% of the sample, food advertisements induce product consumerism, most commonly sweets and fast foods. Buying or asking to buy food after seeing it on the television was associated with fried foods (OR = 1.36, 95%CI = 1.03- 1.79), sweets (OR = 1.69, 95%CI = 1.30-2.18), and snacks (OR = 1.57, 95%CI = 1.12-2.22). CONCLUSION: Food advertisements were associated with greater consumption of fried foods, sweets, and snacks in adolescents, even after adjusting for confounding factors. Univ Estadual Paulista, Fac Ciencias & Tecnol, Programa Posgrad Ciencias Motricidade, Presidente Prudente, SP, Brazil Univ Fed Santa Catarina, Ctr Desportos, Dept Educ Fis, Florianopolis, SC, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Programa Posgrad Fisioterapia, Presidente Prudente, SP, Brazil Univ Porto, Fac Desporto, Ctr Invest Actividade Fis Saude & Lazer, Porto, Portugal Univ Estadual Paulista, Fac Ciencias & Tecnol, Dept Educ Fis, Presidente Prudente, SP, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Programa Posgrad Ciencias Motricidade, Presidente Prudente, SP, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Programa Posgrad Fisioterapia, Presidente Prudente, SP, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Dept Educ Fis, Presidente Prudente, SP, Brazil CAPES: 001

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series., The authors would like to thank patients and controls who participated in this project. The Genome Research @ Fundacio ACE project (GR@ACE) is supported by Fundacion bancaria La Caixa, Grifols SA, Fundacio ACE, and ISCIII (Ministry of Health, Spain). They also want to thank the private sponsors who support the basic and clinical projects of our institution (Piramal AG, Laboratorios Echevarne, Araclon Biotech S.A., and Fundacio ACE). They are indebted to the Trinitat Port-Carbo legacy and her family for their support of Fundacio ACE research programs. Fundacio ACE is a participating center in the Dementia Genetics Spanish Consortium (DEGESCO). A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, and PI17/01474. Accion Estrategica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de Hacer Europa). L.M.R. is supported by Consejeria de Salud de la Junta de Andalucia (grant PI-0001/2017). Control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed after standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The present work was performed as part of the Biochemistry, Molecular Biology, and Biomedicine doctoral program of S. MorenoGrau at Universitat Autonoma de Barcelona (Barcelona, Spain).r Data collection and sharing for this project was partially funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, as well as through generous contributions from the following: AbbVie; the Alzheimer's Association; the Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California.; r The AddNeuroMed data are from a public-private partnership supported by EFPIA companies and SMEs as part of InnoMed (Innovative Medicines in Europe), an integrated project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5. Clinical leads responsible for data collection are Iwona K1oszewska (Lodz), Simon Lovestone (London), Patrizia Mecocci (Perugia), Hilkka Soininen (Kuopio), Magda Tsolaki (Thessaloniki), and Bruno Vellas (Toulouse). Imaging leads are Andy Simmons (London), Lars-Olad Wahlund (Stockholm), and Christian Spenger (Zurich). Bioinformatics leads are Richard Dobson (London) and Stephen Newhouse (London).r Funding support for the Alzheimer's Disease Genetics Consortium (ADGC) was provided through the NIA Division of Neuroscience (U01-AG032984).r The Mayo Clinic Alzheimer's Disease Genetic Studies, led by Dr. Nilufer Ertekin-Taner and Dr. Steven G. Younkin at the Mayo Clinic in Jacksonville, FL, used samples from the Mayo Clinic Study of Aging, the Mayo Clinic Alzheimer's Disease Research Center, and the Mayo Clinic Brain Bank. Data collection was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, and R01 AG003949, NINDS grant R01 NS080820, the CurePSP Foundation, and support from the Mayo Foundation.r The Neocodex-Murcia study was funded by the Fundacion Alzheimur (Murcia), the Ministerio de Educacion y Ciencia (Gobierno de Espana), Corporacion Tecnologica de Andalucia, Agencia IDEA (Consejeria de Innovacion, Junta de Andalucia), the Diabetes Research Laboratory, and the Biomedical Research Foundation. University Hospital Clinico San Carlos has been supported by CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM); CIBERDEM is an ISCIII Project.r The ROS/MAP study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984 and U01AG46152, the Illinois Department of Public Health, and the Translational Genomics Research Institute.r The TGEN study was supported by Kronos Life Science Laboratories, the National Institute on Aging (Arizona Alzheimer's Disease Center grants P30 AG19610 and RO1 AG023193, the Mayo Clinic Alzheimer's Disease Center grant P50 AG16574, and the Intramural Research Program), the National Alzheimer's Coordinating Center (U01 AG016976), and the state of Arizona.r The authors thank the International Genomics of Alzheimer's Project (IGAP) for providing summary result data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i-Select chip was funded by the French National Foundation on Alzheimer's disease and related disorders. European Alzheimer's Disease Initiative (EADI) was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universite de Lille 2, and the Lille University Hospital. GERAD was supported by the Medical Research Council (grant no. 503480), Alzheimer's Research UK (grant no. 503176), the Wellcome Trust (grant no. 082604/2/07/Z), and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant no.; 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01-AG12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC-10-196728.

Background Peripheral biomarkers that identify individuals at risk of developing Alzheimer’s disease (AD) or predicting high amyloid beta (Aβ) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aβ species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. Methods The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aβ40 and Aβ42 peptides. The association between Aβ40 and Aβ42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aβ levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aβ plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. Results FBB-PET global SUVR correlated weakly but significantly with Aβ42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aβ measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aβ FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aβ measurements (p value for interaction = 0.105). Conclusion Brain and plasma Aβ levels are partially correlated in individuals diagnosed with SCD. Aβ plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted. Electronic supplementary material The online version of this article (10.1186/s13195-018-0444-1) contains supplementary material, which is available to authorized users.

Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy.

Blood flow restriction (BFR) training stimulates muscle size and strength by increasing muscle activation, accumulation of metabolites and muscle swelling. This method has been used in different populations, but no studies have evaluated the effects of training on muscle power and submaximal strength (SS) in accounted for the menstrual cycle. The aim of this study was to analyse the effect of strength training (ST) with BFR on the muscle power and SS of upper and lower limbs in eumenorrheic women. Forty untrained women (18-40 years) were divided randomly and proportionally into four groups: (i) high-intensity ST at 80% of 1RM (HI), (ii) low-intensity ST at 20% of 1RM combined with partial blood flow restriction (LI + BFR), (iii) low-intensity ST at 20% of 1RM (LI) and d) control group (CG). Each training group performed eight training sessions. Tests with a medicine ball (MB), horizontal jump (HJ), vertical jump (VJ), biceps curls (BC) and knee extension (KE) were performed during the 1st day follicular phase (FP), 14th day (ovulatory phase) and 26-28th days (luteal phase) of the menstrual cycle. There was no significant difference among groups in terms of the MB, HJ, VJ or BC results at any time point (P>0·05). SS in the KE exercise was significantly greater in the LI + BFR group compared to the CG group (P = 0·014) during the LP. Therefore, ST with BFR does not appear to improve the power of upper and lower limbs and may be an alternative to improve the SS of lower limbs of eumenorrheic women.

The aim of this article is to evaluate the use of musculoskeletal ultrasound in the daily clinical practice of a rheumatology unit. We conducted a descriptive retrospective analysis of the ultrasound examinations performed during 2011 and a comparison of these examinations with those performed between 1998 and 2003 and between 2007 and 2008. A total of 712 ultrasound examinations performed in 2011 were reviewed. Out of the total, examinations of individual areas of the body represented 11.6% versus 45.9% of the examinations made between 2007 and 2008 and 100% of those performed before 2003. The remaining 88.4% of ultrasound examinations performed in 2011 were intended to investigate inflammation in 25.8%, differential diagnosis of arthralgia in 17.1%, enthesis in 12.6% and temporal arteries in 17.3%, and to conduct ultrasound-guided procedures in 10.6% and study microcrystalline pathologies in 4.7%. In our unit, ultrasonography is evolving from being a mere investigation of individual areas of the body to becoming a clinical information tool, which contributes to the diagnosis and monitoring of the disease activity in the patient as a whole.

Disc degeneration alters disc height and mechanics of the spinal column and is associated with lower back pain. In preclinical studies gel-like materials or resorbable polymer-based implants are frequently used to rebuild the nucleus pulposus, aiming at tissue regeneration and restoration of tissue function. To compare the outcome of tissue repair, freeze-dried resorbable polyglycolic acid–hyaluronan (PGA/HA) implants without any bioactive components or bioactivated fibrin (fibrin-serum) was used in a degenerated disc disease model in New Zealand white rabbits. Animals with partial nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity in the nuclear region of operated discs as assessed by magnet resonance imaging was reduced in operated compared to healthy discs, indicating loss of water and did not change from week 1 to month 6 after surgery. Quantification of histological and immunohistochemical staining indicated that the implantation of PGA/HA leads to significantly more repair tissue compared to nucleotomy only. Type II collagen content of the repair tissue formed after PGA/HA or fibrin-serum treatment is significantly increased compared to controls with nucleotomy only. The data indicate that intervertebral disc augmentation after nucleotomy has a positive effect on repair tissue formation and type II collagen deposition as shown in the rabbit model.

Introduction Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods We evaluated apolipoprotein E ( APOE ) e4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE e4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion The FACEHBI sample presents APOE e4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

The purpose of this study was to analyze the clinical and radiological evolution of the total knee revision arthroplasty with cemented stems in patients over 75 years.A retrospective analysis was performed in all the subjects who underwent revision of total knee arthroplasty with cemented stems between 2008 and 2014 in our center. Twenty-seven individuals over 75 years met the inclusion criteria. We assessed the Knee Society Score and range of motion for clinical outcome. We evaluated the implant stability with radiographs through radiolucent lines according to the modified radiological scale of the Knee Society; we registered the complications and prosthetic survival.With an average age of our participants of 82.6 ± 4.4 years and a follow-up of 43 ± 14.4 months, we did not find any mechanical failure of the components. The functional average score was 115 ± 32 in the total KSS, of which 77 ± 17.5 points were in the KSS knee and 42 ± 24 in the KSS function. The average range of motion was 98º ± 17. Radiologically, 18 patients presented radiolucent lines, but only three needed follow-up using the modified Knee Society radiographic scoring system.The results revealed that cemented stems are a good method for fixation in the revision of total knee arthroplasty in people over 75 years. We observed acceptable medium-term clinical results with a low risk of radiological failure, despite the high number of radiolucencies.Analizar la evolución funcional y radiológica de los pacientes mayores de 75 años intervenidos de cirugía de revisión de rodilla con vástagos cementados.

We report a new clinical manifestation of neonatal Behcet's disease. A newborn from a mother with active Behcet's disease during pregnancy, who develops vasomotor phenomena (Raynaud) with oral ulcerations in the second day of life. Neonatal mucocutaneous lesions have been reported previously in few newborns of pregnant women with active Behcet disease. Although neonatal disease is a very infrequent situation, with a mostly transient and favorable course, clinicians should be aware of serious potential complications associated with this entity.

Effective screening for pre-eclampsia resulting in delivery37 weeks' gestation (preterm PE) is provided by assessment of a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) at 11-13 or 19-24 weeks' gestation. This study explores the possibility of carrying out routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of UtA-PI and PlGF for a subgroup of the population, selected on the basis of the risk derived from screening by maternal factors and MAP alone.Study data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 11-13 and/or 19-24 weeks' gestation. Bayes' theorem was used to derive the a-priori risk for preterm PE from maternal factors and MAP. The posterior risk was obtained by the addition of UtA-PI and PlGF. We estimated the detection rate (DR) of preterm PE, at an overall false-positive rate (FPR) of 10%, from a policy in which first-stage screening by a combination of maternal factors and MAP defines screen-positive, screen-negative and intermediate-risk groups, with the latter undergoing second-stage screening by UtA-PI and PlGF.At 11-13 weeks' gestation, the model-based DR of preterm PE, at a 10% FPR, when screening the whole population by maternal factors, MAP, UtA-PI and PlGF was 74%. A similar DR was achieved by two-stage screening, with screening by maternal factors and MAP in the first stage and reserving measurement of UtA-PI and PlGF for the second stage and for only 50% of the population. If second-stage screening was offered to 30% of the population, there would be only a small reduction in DR from 74% to 71%. At 19-24 weeks, the model-based DR of preterm PE, at a 10% FPR, when screening the whole population by maternal factors, MAP, UtA-PI and PlGF was 84%. A similar DR was achieved by two-stage screening with measurements of UtA-PI and PlGF in only 70% of the population; if second-stage screening was offered to 40% of the population, the DR would be reduced from 84% to 81%.High DR of preterm PE can be achieved by two-stage screening in the first and second trimesters with maternal factors and MAP in the whole population and measurements of UtA-PI and PlGF in only some of the pregnancies. Copyright © 2015 ISUOG. Published by John WileySons Ltd.

Removal of injured/damaged meniscus, a vital fibrocartilaginous load-bearing tissue, impairs normal knee function and predisposes patients to osteoarthritis. Meniscus tissue engineering solution is one option to improve outcomes and relieve pain. In an attempt to fabricate knee meniscus grafts three layered wedge shaped silk meniscal scaffold system was engineered to mimic native meniscus architecture. The scaffolds were seeded with human fibroblasts (outside) and chondrocytes (inside) in a spatial separated mode similar to native tissue, in order to generate meniscus-like tissue in vitro. In chondrogenic culture in the presence of TGF-b3, cell seeded constructs increased in cellularity and extracellular matrix (ECM) content. Histology and Immunohistochemistry confirmed maintenance of chondrocytic phenotype with higher levels of sulphated glycosaminoglycans (sGAG) and collagen types I and II. Improved scaffold mechanical properties along with ECM alignment with time in culture suggest this multiporous silk construct as a useful micro-patterned template for directed tissue growth with respect to form and function of meniscus-like tissue.

The purpose of this study was to examine the utility and feasibility of using alternative anterior reference leads when measuring left posterior tibial nerve somatosensory evoked potentials (SEPs). With IRB approval, 12 patients were monitored using both traditional (FPz and C4′) and alternative anterior (F3 and F4) reference leads during routine spine surgery with SEP monitoring. Recordings from the routine and novel electrode pairs were collected and analyzed. All of the SEP amplitudes measured were of similar magnitude except for that of F3–F4, which was significantly lower (P

A population pharmacokinetics analysis was performed after intravenous ganciclovir and oral valganciclovir in solid organ transplant patients with cytomegalovirus. Patients received ganciclovir at 5 mg/kg of body weight (5 days) and then 900 mg of valganciclovir (16 days), both twice daily with dose adjustment for renal function. A total of 382 serum concentrations from days 5 and 15 were analyzed with NONMEM VI. Renal function given by creatinine clearance (CL CR ) was the most influential covariate in CL. The final pharmacokinetic parameters were as follows: ganciclovir clearance (CL) was 7.49·(CL CR /57) liter/h (57 was the mean population value of CL CR ); the central and peripheral distribution volumes were 31.9 liters and 32.0 liters, respectively; intercompartmental clearance was 10.2 liter/h; the first-order absorption rate constant was 0.895 h −1 ; bioavailability was 0.825; and lag time was 0.382 h. The CL CR was the best predictor of CL, making dose adjustment by this covariate important to achieve the most efficacious ganciclovir exposure.

We identified 14 cases of Legionnaires' disease occurring in 2946 solid organ transplant recipients from 1985 to 2007. Most cases were sporadic and community acquired. The recent introduction of the urinary antigen test has accelerated diagnosis and allows prompt institution of adequate therapy. The overall mortality rate in our series was 14.3%.

Procollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the prototype of a small group of proteases that have key roles in extracellular matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related proteases TLL-1 and TLL-2 are considered as promising drug targets for the treatment of excessive fibrosis and muscle wasting. We report here the crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation of a cysteine-rich loop within the active site, and suggest that a flap movement is required in order to allow substrate binding. On the basis of these substantial differences between the BMP-1 and astacin active sites, a structural basis for their differing substrate specificities is proposed.

Diffusion tensor imaging (DTI) and tractography provide the neurosurgeon with a valid 3D view of the white matter tracts of the brain for the presurgical planning of the treatment of lesions close to eloquent areas, this being one of the principal clinical applications of this technique. In this article, we describe through practical cases the anatomic relationships of white matter tracts that are essential for language and reading, based on DTI studies and the excellent anatomic correlation with the intraoperative subcortical map.

Background: The role of the striatum in language remains poorly understood. Intraoperative electrical stimulation during surgery for tumours involving the caudate nucleus or putamen in the dominant hemisphere might be illuminating. Objectives: To study the role of these structures in language, with the aim of avoiding postoperative definitive aphasia. Methods: 11 patients with cortico-subcortical low grade gliomas were operated on while awake, and striatal functional mapping was done. Intraoperative direct electrical stimulation was used while the patients carried out motor and naming tasks during the resection. Results: In five cases of glioma involving the dominant putamen, stimulations induced anarthria, while in six cases of glioma involving the dominant caudate, stimulations elicited perseveration. There was no motor effect. The striatum was systematically preserved. Postoperatively, all patients except one had transient dysphasia which resolved within three months. Conclusions: There appear to be two separate basal ganglia systems in language, one mediated by the putamen which might have a motor role, and one by the caudate which might have a role in cognitive control. These findings could have implications for surgical strategy in lesions involving the dominant striatum.

Introduction: Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisite the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG. Methods: From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei. Results: Immunostaining was significantly higher for Ta/T1 G3 ± Cis (p

Objective: Prenatal diagnosis of foetal trisomies is usually performed by cytogenetic analysis. This requires lengthy laboratory procedures and it is expensive. Here, we report a retrospective study of quantitative fluorescent polymerase chain reaction (QF-PCR) for prenatal detection of trisomies 13, 18 and 21. Methods: QF-PCR was performed on a total of 447 amniotic fluids blindly analysed without any knowledge of the cytogenetic results and 43 samples with known karyotype. All samples were tested with at least 4 small tandem repeat markers specific for each chromosome 13, 18 or 21. Results: QF-PCR results on amniotic fluid were consistent with conventional cytogenetic data. QF-PCR detected 5 cases of trisomy 21, 2 cases of trisomy 18, 1 case of trisomy 13 and 1 case with Klinefelter’s syndrome. Conclusions: QF-PCR has proved to be very useful in clinical settings, since it allows the detection of major numerical disorders in a few hours after sampling and thus reduces parental anxiety.

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation.

Summary Correspondence Gabriel Rodrigues Neto, Department of PhysicalEducation – Graduate Program, Federal Universityof Rio de Janeiro, Avenida Pau Brasil, 540 Ilhado Fund~ao, Rio de Janeiro 21941-590, BrazilE-mail: gabrielrodrigues_1988@hotmail.com Accepted for publication Received 22 April 2014;accepted 28 August 2014 Key words acute effects; haemodynamic; ischaemia;postexercise responses; resistance training; vascularocclusion The aim of this study was to compare the acute effect of resistance exercise (RE)with and without blood flow restriction (BFR) on heart rate (HR), double prod-uct (DP), oxygen saturation (SpO 2 ) and rating of perceived exertion (RPE).Twenty-four men (21 79 3 21 years) performed three experimental protocolsin a random order (crossover): (i) high-intensity RE at 80% of 1RM (HI), (ii)low-intensity RE at 20% of 1RM (LI) and (iii) low-intensity RE at 20% of 1RMcombined with partial blood flow restriction (LI+BFR). HR, blood pressure, SpO 2 and RPE were assessed. The data were analysed using repeated measures analysisof variance and the Wilcoxon test for RPE. The results indicated that all protocolssignificantly increased HR, both immediately postexercise and during the subse-quent 60 min (P

The p15 gene which encodes a cyclin-dependent kinase inhibitor, is located in the 9p21 chromosomal region that is frequently deleted in human bladder transitional cell carcinomas (TCCs). The aim of the present paper is to study the potential involvement of the p15 gene in the evolution of TCCs. p15 mRNA expression was investigated by semi-quantitative RT-PCR in a series of 75 TCCs, 13 bladder cell lines and 6 normal bladder urothelia by semi-quantitative RT-PCR. p15 was expressed in the normal urothelium but p15 mRNA levels were significantly decreased in 66% of the superficial (Ta-T1) TCCs (P = 0.0015). In contrast, in muscle-invasive (T2-T4) TCCs, p15 expression differed widely between samples. p16 mRNA levels were also studied and there was no correlation between p15 and p16 mRNA levels, thus indicating that the two genes were regulated independently. Lower p15 expression in superficial tumours did not reflect a switch from quiescence to proliferative activity as normal proliferative urothelial controls did not present decreased p15 mRNA levels relative to quiescent normal urothelia. We further investigated the mechanisms underlying p15 down regulation. Homozygous deletions of the p15 gene, also involving the contiguous p16 gene, were observed in 42% of the TCCs with decreased p15 expression. No hypermethylation at multiple methylation-sensitive restriction sites in the 5′-CpG island of p15 was encountered in the remaining tumours. Our data suggest that decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium and that a mechanism other than homozygous deletions or hypermethylation, may be involved in p15 down regulation. © 2001 Cancer Research Campaign http://www.bjcancer.com

Computed tomography studies are usually used to assess patients with pleural effusions, and radiologists should be aware of the significance of different CT findings for the diagnosis of the effusion. The purpose of this study was to evaluate CT findings for etiological diagnosis of pleural effusions. Contrast-enhanced CT of the chest of 211 patients with pleural effusion of definite diagnosis were evaluated. The CT images were evaluated for the presence and extent of pleural effusion, thickening or nodules, extrapleural fat and other changes in the mediastinum or lung. The CT scans were read by two independent observers and correlation between them was evaluated. Comparison of CT findings between benign and malignant effusions, between exudates and transudates, and between empyemas and the other parapneumonic effusions were carried out. Kappa values for most CT findings were > 0.85. Loculation, pleural thickening, pleural nodules, and extrapleural fat of increased density were only present in exudative effusions. Multiple pleural nodules and nodular pleural thickening were the only pleural findings limited to malignant pleural effusions. The signs were also more frequently seen in empyemas than in other parapneumonic effusions. Computed tomography findings can help to distinguish between transudates and exudates. Although there is some overlap between benign and malignant pleural effusions, pleural nodules and nodular pleural thickening were present almost exclusively in the latter. Although differences between CT findings of empyemas and the other parapneumonic effusions exist, there is no finding which can definitely differentiate between them.

To compare the analgesic efficacy of epidural infusions of levobupivacaine, bupivacaine and ropivacaine in labor.102 nulliparous parturients in early labor were enrolled in this randomized, double-blind clinical trial. They were randomly assigned to receive one of three continuous epidural infusion regimens: levobupivacaine 0.125%, bupivacaine 0.125% or ropivacaine 0.2%, all with fentanyl 1 microg/mL at 8 mL/h. Supplementary analgesia was provided with an 8-mL epidural bolus of the study solution if visual analogue scale (VAS) score for pain was 40 (0-100 mm). Pain and motor and sensory block were measured at 0, 15 and 30 min, 1, 2, 3 and 4h and full cervical dilatation.Analgesia was satisfactory in all three groups, with VAS score40 mm at all measurements. VAS scores were greater in those receiving levobupivacaine (P0.005). Motor block was greater with bupivacaine than levobupivacaine (P0.01). There were no differences in motor block between levobupivacaine and ropivacaine. There were no other differences between groups.All three regimens were effective during first stage of labor although pain scores were higher in those receiving levobupivacaine. Motor block was greater with bupivacaine than with levobupivacaine.

The efficacy and safety of intrathecal magnesium as analgesic adjuvant has been tested by several clinical trials in recent years. We performed a meta-analysis of the available literature.Randomized clinical trials comparing a 50 to 100 mg dose of intrathecal magnesium sulfate versus placebo in addition to an intrathecal local anesthetic and/or opiate for a below-umbilicus procedure were included. Medline, LILACS, Cochrane Library and Google Scholar databases were searched. A random analysis was performed and heterogeneity was tested for. The size of the effect for quantitative outcomes was calculated as standard mean difference (SMD, neutral=0); and as odds ratio (OR, neutral=1) for dichotomous outcomes.Twelve studies totaling 817 patients were included. The "time to first analgesia request" was at least 35 minutes longer when intrathecal magnesium was included in the intervention (SDM 0.94, 95%CI 0.51 to 1.37, P0.001). The "onset time to sensory block" (SDM 0.64, 95%CI 0.15 to 1.12, P=0.01) and the "time to maximal motor block" (SDM 0.97, 95%CI 0.28 to 1.67, P=0.006) were 2.4 minutes slower with intrathecal magnesium. There was no difference in "time to full motor recovery, incidence of pruritus, postoperative nausea and vomiting, bradicardia, low blood pressure and urinary retention". No cases of respiratory depression or neurotoxicity were recorded in these studies.The inclusion of 50 to 100 mg of intrathecal magnesium in a spinal anesthetic prolongs opiate analgesia duration; no safety concerns have been identified by the included clinical studies but additional evidence is advised.

Biofilm formation on external ventricular drainages (EVDs) has been postulated as the main pathogenic mechanism for EVD-associated ventriculitis. However, biofilm on EVDs has never been systematically studied and the in vivo effect of antibiotic-impregnated EVDs on biofilm has not been assessed. The aim of this study was to measure the prevalence of biofilm formation on EVDs and to analyze the influence of antibiotic-impregnated EVD on the risk of biofilm formation and ventriculitis. Consecutive patients with EVDs were included in the study. Surveillance cerebrospinal fluid (CSF) cultures were performed twice a week. Withdrawn EVDs were cultured using standard bacteriologic techniques and examined under a scanning electron microscope. We collected 32 EVDs, 18 of which (56 %) were antibiotic-impregnated EVDs. Biofilm was present on 24 EVDs (75 %), ventriculitis was diagnosed in 6 patients (19 %), and colonization occurred in 12 patients (38 %). All cases of ventriculitis were due to Gram-negative bacteria. Biofilm was more frequent on EVDs originating from patients with ventriculitis or bacterial colonization. Impregnated EVDs did not avoid ventriculitis or colonization, but biofilm development on these devices depended on the time from insertion and varied from 67 % for those used for

Background and purpose Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. Methods Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aβ42, total-tau, phosphorylated-tau181) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. Results Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P

Isolated long bone fractures are unusual and may be missed in the initial X-rays, especially when they are minimally displaced. The delayed treatment of these fractures may cause various complications, such as delayed bone healing or seudoarthrosis, which are difficult to manage. Our clinical case shows delayed healing in a long bone fracture and how the radiologic course may assist in the therapeutic management of this complication.

Numerous investigators have suggested that cell glycoconjugates are modified by the development of cancer and the progression of this to a malignant form. Accordingly, in the present work, beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were studied in human thyroid and gastric tumours. Samples were obtained from human gastric mucosa and thyroid gland tumours together with a part of the surrounding normal tissue (control). Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from suitable p-nitrophenyl-derivative substrates. Results showed that beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were detected in tumour and control samples from thyroid and gastric tissues. The gastric mucosa also showed alpha-L-mannosidase activity. The specific activities of these glycosidases were higher (two- or three-fold) in tumour tissues as compared with their controls. beta-D-galactosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities from thyroid and gastric tumours showed a significant increase in V(max) as compared with their respective controls (P0.05 or P0.001). Thyroid alpha-L-fucosidase activity showed a statistically and significantly increased affinity (lower K(m)) in tumour samples as compared to normal tissue. In conclusion both gastric and thyroid tumours showed enhanced glycosidase activity as compared with enzyme activity observed in normal tissue. These results are in agreement with the notion of a markedly raised degradation within lysosomes of tumour cells.

A prospective virologic follow-up of solid organ transplant patients was designed to determine the usefulness of antigenemia and viremia as virologic markers for the diagnosis of cytomegalovirus (CMV) infections, and also for monitoring CMV disease and therapy control. A total of 629 blood samples from 127 patients (60 liver, 47 kidney, and 20 heart transplant recipients) were studied by tube and shell vial cultures, and by antigenemia assay. This later was carried out by an indirect immunofluorescent assay method for formalin-fixed cytospin slides containing 2 x 10(5) leukocytes, using a monoclonal antibody directed against the CMV pp65 antigen. CMV was detected by at least one of the three methods in 238 specimens (37.8%) from a total of 63 patients. The antigenemia assay was positive in 215 (90.3% of positive samples). A total of 94 samples were detected only by this marker, which occurred either in samples with low positive counts (70.2% with antigenemia counts10 positive cells/10(5) leukocytes) or in specimens from treated patients. There were 30 episodes of CMV disease in 23 patients. Antigenemia was positive in all these episodes, 27 of them with counts20 positive cells/10(5) leukocytes. With this cut-off, positive and negative predictive values for symptomatic CMV infection were 100% and 97.2%, respectively. The antigenemia assay is a rapid, sensitive, specific, and early marker of CMV infection in transplantees. Cultures became negative with antiviral therapy while remaining antigenemia detectable. There was an association between highest quantitative antigenemia test results and clinical symptoms in our patients. In its quantitative version, the assay is useful to detect symptomatic infection and appears to be a helpful tool in managing patients at risk and in guiding antiviral therapy.

Background/Aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level. Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.

Although endoscopic thyroid surgery is gaining wide acceptance, however, manual endoscopic operation also has shown several limitations. The advent of robotic surgical systems, such as the da Vinci surgical system (Intuitive Surgical, Mountain View, CA, USA), is expected to make it possible to overcome some limitations of manual endoscopic operation. Herein we report a single surgeon (H.Y.K.)'s initial two-year experience of new robotic thyroid operations using the bilateral axillo-breast approach (BABA), the approach which has definite advantages and recently has been widely used for the traditional endoscopic thyroid surgery.Between July 2008 and July 2010, 93 patients underwent robotic thyroid surgery using the BABA, with the da Vinci-S surgical system, at the Korea University Anam Hospital, Seoul, Korea. The data on the patients' clinicopathological characteristics, operation types, operation times, surgical results, postoperative hospital stays and complications were collected in a prospective manner, and later evaluated.Seventy-two total thyroidectomies with or without central neck dissections mostly for the papillary carcinomas, twenty lobectomies with or without central neck dissections for the minute ‑ smaller than 0.5 cm in their maximal diameter ‑ papillary carcinomas, follicular neoplasms and benign tumors, and a bilateral subtotal lobectomy for the multinodular goiter were performed robotically. There was no conversion of robotic procedure to traditional endoscopic or open procedure. The mean total operation time was 288.5±48.0 minutes. The mean number of retrieved lymph nodes by the central neck dissection was 5.1±1.97 (range, 0-12). The mean hospital stay of the patients was 2.8±1.2 days. And the mean postoperative 3rd month serum thyroglobulin level in patients undergone total thyroidectomy was 0.3±0.14 ng/mL (range, 0.08-1.95). Three (3.2%) patients suffered from transient hoarseness postoperatively, but all of them recovered in three months. Transient hypocalcemias were observed in 17 out of 72 (23.6%) patients who had undergone total thyroidectomy, but none of them left permanent. No other complication, such as bleeding, infection, neither fluid collection, was observed.Our initial surgical results of robotic thyroid surgery using BABA demonstrate the feasibility and safety of the procedure in the treatment of benign tumors and early differentiated carcinomas.

To determine the incidence of acute coronary syndrome (ACS) with and without ST-segment elevation, factors related to the development of ACS, mean hospital stay, and attributable mortality.In a noncardiac surgery cohort attended in the postoperative critical care unit of Hospital General de la Ciudad Real, Spain, data were recorded prospectively between April 2006 and December 2009. The incidence of symptomatic ACS was calculated.Thirty-two of 1919 patients developed ACS (incidence, 1.7%). Patient factors related to developing the syndrome were male sex (P=.046), age (P=.001), arterial hypertension (68.8%, P=.012), and a history of ischemic heart disease (34.4%, P=.001). Types of surgery that were significantly related to developing ACS were general surgery (37.5%), orthopedic or trauma surgery (28.1%), and vascular surgery (15.6%) (P.004). Twenty percent of the cohort received transfusions; 50% of those who developed ACS were transfused (P=.001). The condition was treated medically in 87.5% of the cases. The mean (SD) duration of hospital stay was 2.96 (6.3) days for the cohort and 3.88 (5) days for patients who developed ACS (P=.39); mortality rates were 5% and 6%, respectively (P=.45). Multivariate analysis confirmed that the following independent variables were associated with developing postoperative ACS: a history of ischemic heart disease (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.98-10.62) and intraoperative bleeding (OR, 3.18; 95% CI, 1.51-6.71). Gynecologic surgery patients were the least likely to develop postoperative ACS (OR, 0.063; 95% CI, 0.004-1.09).The incidence of postoperative ACS in this noncardiac surgery cohort was 1.7%. Age, male sex, a history of arterial hypertension or ischemic heart disease, type of surgery, and intraoperative bleeding requiring transfusion of packed red blood cells are factors that are associated with developing this complication. Given the seriousness of ACS it is important to classify patients by risk before surgery.