"Live High-Train Low and High" Hypoxic Training Improves Team-Sport Performance.

PURPOSE: This study aims to investigate physical performance and hematological changes in 32 elite male team-sport players after 14 d of "live high-train low" (LHTL) training in normobaric hypoxia (≥14 h·d at 2800-3000 m) combined with repeated-sprint training (six sessions of four sets of 5 × 5-s sprints with 25 s of passive recovery) either in normobaric hypoxia at 3000 m (LHTL + RSH, namely, LHTLH; n = 11) or in normoxia (LHTL + RSN, namely, LHTL; n = 12) compared with controlled "live low-train low" (LLTL; n = 9) training. METHODS: Before (Pre), immediately after (Post-1), and 3 wk after (Post-2) the intervention, hemoglobin mass (Hbmass) was measured in duplicate [optimized carbon monoxide (CO) rebreathing method], and vertical jump, repeated-sprint (8 × 20 m-20 s recovery), and Yo-Yo Intermittent Recovery level 2 (YYIR2) performances were tested. RESULTS: Both hypoxic groups similarly increased their Hbmass at Post-1 and Post-2 in reference to Pre (LHTLH: +4.0%, P < 0.001 and +2.7%, P < 0.01; LHTL: +3.0% and +3.0%, both P < 0.001), whereas no change occurred in LLTL. Compared with Pre, YYIR2 performance increased by ∼21% at Post-1 (P < 0.01) and by ∼45% at Post-2 (P < 0.001), with no difference between the two intervention groups (vs no change in LLTL). From Pre to Post-1, cumulated sprint time decreased in LHTLH (-3.6%, P < 0.001) and LHTL (-1.9%, P < 0.01), but not in LLTL (-0.7%), and remained significantly reduced at Post-2 (-3.5%, P < 0.001) in LHTLH only. Vertical jump performance did not change. CONCLUSIONS: "Live high-train low and high" hypoxic training interspersed with repeated sprints in hypoxia for 14 d (in season) increases the Hbmass, YYIR2 performance, and repeated-sprint ability of elite field team-sport players, with benefits lasting for at least 3 wk postintervention.

Jauhinterien valmistuksen kehittäminen

Diplomityö käsittelee eräälle paperiteollisuuden komponentteja valmistavalle yritykselle tehtyä tutkimusta, jossa tutkittiin erilaisia valmistusmenetelmiä, joilla voidaan valmistaa uudenlaisia jauhinteriä. Diplomityössä ideoitiin erilaisia jauhinteränkonstruktiovaihtoehtoja. Vaihtoehtoja havainnollistamaan piirrettiin jokaisesta ratkaisusta 3D- mallit. Vaihtoehtojen pohjalta päätettiin suoritettavat valmistustestaukset. Työssä suoritettiin valmistustestejä kuitulaserilla, hiilidioksidilaserilla sekä hienosädeplasmalla. Näiden testien perusteella saatiin näkemys siitä, mikä konstruktiovaihto on valmistusteknisesti paras, täyttäen samalla jauhinterälle asetetut vaatimukset. Diplomityön tuloksena syntyi toimiva ja kustannustehokas ratkaisu jauhinterien valmistamiseksi.

Reversal of a full-length mutant huntingtin neuronal cell phenotypeby chemical inhibitors of polyglutamine-mediated aggregation

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotypephenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expressionof mutant huntingtin in a striatal cell line from the HdhQ111/Q111 knock-in mouse. Results: We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1¿171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 ¿M, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant HdhQ111/Q111 striatal cells. Conclusions: At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin.

Long term trends in prevalence of neural tube defects in Europe: population based study.

STUDY QUESTION: What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist? METHODS: This was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends. SUMMARY ANSWER AND LIMITATIONS: Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD. WHAT THIS STUDY ADDS: In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification. FUNDING, COMPETING INTERESTS, DATA SHARING: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.

Controle de qualidade de monitores de diagnóstico por imagem e iluminância nos espaços de pós-processamento em serviços de imagiologia

OBJETIVO: Avaliar a qualidade dos monitores de diagnóstico e tratamento de imagem digital em radiologia convencional (raios X) com base nos níveis de luminância. Fez-se a medição da iluminância dos postos de trabalho onde estavam os monitores. MATERIAIS E MÉTODOS: A medição da luminância foi realizada usando-se um detector Unfors Xi Light em cinco instituições, com 23 monitores primários e 22 secundários, sendo 6 usados em urgência, seguindo o método descrito no relatório TG18 da American Association of Physicists in Medicine (AAPM). O instrumento de medida utilizado foi o Delta Ohm HD 9221 luximeter. RESULTADOS: Para as recomendações da AAPM, tanto monitores primários como secundários cumpriram, no geral, os níveis de tolerância. No caso dos níveis de iluminância, nos locais de trabalho dos monitores primários encontravam-se ligeiramente acima do intervalo recomendado. Quanto às recomendações do The Royal College of Radiologists (RCR), os monitores que respeitaram os níveis recomendados estavam em minoria, embora as diferenças não fossem significativas. CONCLUSÃO: Em geral, os resultados foram satisfatórios, embora os monitores não fossem adequados para atingir as recomendações exigentes do RCR. Os níveis de referência entre os monitores primários e secundários deveriam aproximar-se, de modo a garantir a qualidade de imagem. Os monitores para visualização e diagnóstico de imagens médicas devem ser regularmente avaliados para manter um sistema com a qualidade exigida, dada a função que desempenham.

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

Treatment-related renal side-effects in pediatric cancer patients

Background: The long-term side-effects of cancer treatments are of growing importance, since the number of pediatric cancer survivors has considerably increased. Renal side-effects should be noted early to prevent further deterioration. Renal dysfunction may also develop long after cancer treatment. Easy and reliable methods for assessing renal function are needed. Aims: The aims were to find the mechanisms behind methotrexate-induced renal damage by studying renal tubular cells (LLC-PK1cells), and to evaluate the usefulness of laboratory tests in assessing glomerular function in pediatric cancer patients by comparing an isotope clearance method with alternative methods. The aim was also to study the long-term effects of bone marrow transplantation (BMT) and high-dose methotrexate (HD-MTX) treatment in renal function. Results: Methotrexate induced time-dependent renal tubular cell swelling and cell death. In patients treated with HD-MTX a significant decrease in GFR was noted after a follow-up time of one to ten years. One year after BMTthe GFR was reduced, especially in patients treated with total body irradiation (TBI). GFR recovered slightly but remained stable thereafter. In glomerular function assessment the serum cystatin C (cysC) concentration showed a significant association with GFR measured by the isotope method. Conclusions: Methotrexate induced acute damage in renal tubular cells. In assessing GFR the isotope method still remains the method of choice, but the assay of cystatin C was the most reliable of other alternatives. Long-term follow-up of renal function is needed in BMT patients and patients treated with HD-MTX.

Determinação da 2,5-hexanodiona em amostras de urina submetidas à hidrólise ácida: importância da coluna cromatográfica e do pH do meio

Acidic hydrolysis of samples is frequent in urinary 2,5-hexanodione determination. This hydrolysis should be performed under proper conditions, in order to avoid interference, such as the presence of 2,5-dimethylfurane and 2-acetylfurane. The results of the present work, as well as data from the literature, show that the use of non-polar or slightly polar chromatographic columns of 30 m length is an essential condition for 2,5-HD determination in an acid hydrolysed urine sample. In the same way the pH should be kept between 0.3 and 0.5. The mean concentrations of 2,5-HD in samples submitted to hydrolysis (0.50 ± 0.28 mg/g of creatinine) was about 3 times higher than those found in the samples without acid hydrolysis (0.19 ± 0.3 mg/g of creatinine).

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

The aim of the present study was to determine 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, by gas chromatography/flame ionization detection in 31 workers exposed to n-hexane after two types of sample pretreatment, i.e., with (total 2,5-HD) and without (free 2,5-HD) acid hydrolysis. The mean urinary 2,5-HD was 0.52 mg/L (free) and 2.88 mg/L (total), this difference being significant (Student t-test, p < 0.05). The differences in the results according to the sample treatment support the need to modify the current Brazilian legislation, which proposes the analysis of 2,5-HD without indicating whether it is the free or total metabolite.

Is contextual-potentiated eating dependent on caloric density of food?

One experiment tested whether a specific context could elicit eating in rats as a result of Pavlovian conditioning and whether this effect depended on the caloric density of food. Thirty two deprived rats experienced two contexts. They had access to food in context A, but no food was available in context B. During conditioning, half of the animals received high density caloric food (HD groups) whereas the other half, low density caloric food (LD groups). Then, half of the rats in each type of food group was tested in context A and the other half in context B. The results demonstrated an effect of context conditioning only in HD groups. These findings suggest the relevance of both contextual conditioning and caloric density of food in eating behaviour. Implications for the aetiology of binge eating will be discussed.

Importância das variáveis altura dominante e altura total em equaçõea hipsométricas e volumétricas

Este estudo foi conduzido, visando avaliar as seguintes hipóteses: a) equações hipsométricas devem ser obtidas por parcela, apenas em função do dap; e b) equações volumétricas devem ser locais, em função apenas do dap. Foram utilizados dados de quatro parcelas distribuídas ao acaso em um povoamento de eucalipto de 67,81 ha e de 50 parcelas distribuídas ao acaso em um povoamento de 121,3 ha, da mesma espécie. Em uma análise inicial, a fim de obter valores reais de altura total e de volume sólido, realizou-se uma cubagem rigorosa de todas as árvores das quatro parcelas. Foram utilizados, ainda, dados de 277 árvores cubadas rigorosamente nos povoamentos. Para avaliar a exatidão das estimativas e as hipóteses formuladas, empregou-se o procedimento estatístico proposto por Leite & Oliveira (2002). Com base nos resultados, as hipóteses a e b foram rejeitadas a 1% de probabilidade. Concluiu-se, portanto, que em um inventário florestal a variável Hd deve ser considerada e que as equações volumétricas devem ser regionais.

Uso de traçadores para avaliação da hidrodinâmica de sistemas alagados construídos operando sob condições climáticas tropicais

Sistemas alagados construídos (SACs) são, atualmente, importante opção para o tratamento de resíduos e controle da poluição pontual e difusa. O uso de SACs tem aumentado ano a ano, entretanto o nível de entendimento da hidrodinâmica do processo não tem crescido na mesma proporção. Traçadores fluorescentes apresentam-se como opção na determinação de curvas de distribuição de tempos de residência (DTR) e de parâmetros hidrodinâmicos, como número de dispersão e eficiência hidráulica. A pesquisa foi realizada com o objetivo de avaliar dois corantes (rodamina WT e fluoresceína sódica) na determinação das características hidrodinâmicas de SACs com escoamento subsuperficial, operando em região de clima tropical. Os tempos de residência experimentais (τR) para os SACs variaram entre 4,5 e 5,0 dias, e os parâmetros de modelos teóricos foram obtidos para cada sistema, indicando dispersões muito pequenas. Os SACs, que apresentavam relação comprimento/largura (L/B) de 24/1, comportaram-se como sistemas de escoamento próximo ao pistonado. Embora a massa total adicionada não tenha sido recuperada (a adsorção é um dos mecanismos de perda), a pesquisa indicou que a rodamina WT pode ser utilizada com resultados satisfatórios na avaliação do comportamento hidrodinâmico de SACs.

Utilização de lisímetros de pesagem para a determinação dos coeficientes de cultura do meloeiro (Cucumis melo L.) para cultivo em estufa agrícola na região de Araras - SP

Esta pesquisa foi conduzida em uma estufa agrícola instalada na área experimental do Centro de Ciências Agrárias da Universidade Federal de São Carlos, localizado em Araras - SP. O solo da área experimental é um Latossolo Vermelho-Escuro, distrófico, de horizonte A moderado e textura argilosa. Os meloeiros estudados foram os híbridos Louis e HD 90. O experimento foi irrigado por gotejamento, e o controle da irrigação, realizado por meio de dois lisímetros de pesagem instalados dentro da estufa. A umidade do solo foi monitorada com uma sonda de TDR e mantida próxima de sua capacidade de campo. As informações climatológicas relevantes ao projeto foram coletadas em estações meteorológicas automáticas, instaladas dentro e fora da estufa. A evapotranspiração de referência (ETo) foi estimada pelos modelos agroclimáticos de Penman-Monteith, Penman, Makkink e do Tanque Classe A. Os consumos totais de água medidos nos lisímetros foram de 254,5 mm e 188,6 mm, respectivamente, para os meloeiros Louis e HD 90, os quais correspondem ao consumo médio diário de 3,18 mm e 2,35 mm. Todos os modelos agroclimáticos avaliados subestimaram a evapotranspiração de referência estimada pelo modelo padrão de Penman-Monteith, variando de um mínimo de 26,9%, no caso do modelo de Penman, até um máximo de 74,3%, no caso do modelo de Makkink. Os coeficientes de cultura determinados pelo modelo padrão de Penman-Monteith, considerando-se aqui o valor médio dos dois tipos de meloeiros estudados, foram os seguintes: estádio inicial: 0,20; estádio intermediário: 1,10, e estádio final: 0,50.