The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity

The ascending midbrain 5-HT neurons to the forebrain may be dysregulated in depression and have a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by coimmunoprecipitation and colocation of the FGFR1 and 5-HT1A immunoreactivities in the midbrain raphe cells, evidence for the existence of FGFR1-5-HT1A receptor heterocomplexes in the dorsal and median raphe nuclei of the Sprague Dawley rat as well as in the rat medullary raphe RN33B cells has been obtained. Especially after combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA clusters was found in the RN33B cells. Similar results were reached with the FRET technique in HEK293T cells, where TM-V of the 5HT1A receptor was found to be part of the receptor interface. The combined treatment with FGF-2 and the 5-HT1A agonist also synergistically increased FGFR1 and ERK1/2 phosphorylation in the raphe midline area of the midbrain and the RN33B cells as well as their differentiation, as seen from development of the increased number and length of extensions per cell and their increased 5-HT immunoreactivity. These signaling and differentiation events were dependent on the receptor interface since they were blocked by incubation with TM-V but not by TM-II. Together, the results indicate that the 5-HT1A autoreceptors by being part of a FGFR1-5-HT1A receptor heterocomplex in the midbrain raphe 5-HT nerve cells appear to have a trophic role in the central 5-HT neuron systems in addition to playing a key role in reducing the firing of these neurons

Kestävän kehityksen näkökulmien huomioiminen kunnan energiaratkaisussa

Diplomityön tavoitteena on tuottaa informaatiota kunnalliseen päätöksentekoon, jonka avulla kestävän kehityksen näkökulmia voidaan huomioida kunnan energiaratkaisusta päätettäessä. Yhtenä työn lähtökohtana on ollut myös uusi EU-direktiivi, jonka mukaan ympäristönäkökohtia voidaan huomioida julkisten hankintojen tarjouspyyntömenettelyssä valintaperusteena. Tarkastelun kohteena oli kokoluokaltaan 0,5–3 MW:n aluelämpölaitokset sekä polttoaineiden tuotantoketjut. Työssä vertailtavat polttoaineet olivat metsähake, raskas polttoöljy, kevyt polttoöljy ja turve. Diplomityössä on perehdytty kestävän kehityksen käsitteeseen ja muodostettu sen mukaan ekologiselle, sosiaaliselle ja taloudelliselle näkökulmalle kunnallisen energiaratkaisun indikaattoreita. Empiirisessä osassa käsitellään kestävän kehityksen näkökulmien muodostumista Enon energiaosuuskunnan toimintaan perustuen. Käytettävät kestävän kehityksen näkökulmien mukaiset indikaattorit ovat polttoaineen tuotannosta ja käytöstä aiheutuvat kasvihuonekaasupäästöt, polttoaineen tuotannon työllisyysvaikutukset sekä energian hinnan muodostuminen osuuskunnan asiakkaille. Tässä diplomityössä tarkastelluilla kestävän kehityksen indikaattoreilla mitattuna, metsähakkeen käytöllä energiantuotannossa on positiivinen vaikutus niin kunnan kasvihuonekaasutaseessa, työllisyystilanteessa sekä myös enemmän kuluttajaystävällinen asema, lämmön hinnan vakauden ansiosta, kuin muilla työssä käsiteltävillä polttoaineilla. Polttoaineen tuotantoketjun osalta metsähakkeelle saatiin tuotannon ja käytön aiheuttamaksi kasvihuonekaasupäästöksi 2,9–4,2 g CO2-ekv/MJ. Tulos perustuu Enon energiaosuuskunnan polttoaineen hankinnassa käytössä oleviin keskimääräisiin etäisyyksiin metsäkuljetuksessa (250 m) ja kaukokuljetuksessa (15 km). Tuotannon ja käytön aiheuttamat kasvihuonekaasupäästöt olivat raskaalla polttoöljyllä 88,2 g CO2-ekv/MJ, kevyellä polttoöljyllä 85,0 g CO2-ekv/MJ ja turpeella 104,0–108,1 g CO2-ekv/MJ. Metsähakkeen osalta polttoaineen tuotannon osuus koko tarkastellun energiaketjun kasvihuonekaasupäästöistä oli noin 43–57 %. Enon energiaosuuskunnan tapauksessa vuoden 2005 odotetulla toiminta-asteella metsähakkeella tuotetun lämmön tuotantoketjun kasvihuonekaasupäästöt ovat noin 160 t CO2-ekv. Kevyellä polttoöljyllä tuotetun lämmön tuotantoketjun kasvihuonekaasupäästöt olisivat noin 3700 t CO2-ekv sekä turpeen (50 %) ja metsähakkeen (50 %) seoskäyttöön perustuvalla ketjulla noin 2300–2400 t CO2-ekv. Samaisella toiminta-asteella työllisyysvaikutukset ovat käytettäessä metsähaketta 2,2–8,6 htv, raakaöljyä 0,12 htv ja turvetta 1,4–1,6 htv. Metsähakkeen käyttö aluelämpölaitosten pääpolttoaineena takaa myös vakaan hintakehityksen osuuskunnan asiakkaille.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.

Caracterização biométrica e respostas fisiológicas de diásporos de murucizeiro a tratamentos para superação da dormência

Diásporos (pirênios) de Byrsonima crassifolia (L.) H.B.K., dos clones Cristo, Santarém 2 e Tocantins 1, do Banco de Germoplasma da Embrapa Amazônia Oriental, foram caracterizados e submetidos a tratamentos pré-germinativos com o objetivo de aumentar a porcentagem e acelerar a germinação das sementes. Na caracterização, foram considerados os seguintes aspectos: massa, comprimento, largura, número de sementes e de lóculos por pirênio e espessura do endocarpo. Os tratamentos para superação da dormência consistiram em: a) pré-embebição dos pirênios em solução de ácido giberélico (500 mg L-1); b) pré-embebição em água seguida de fratura no endocarpo, e c) pré-embebição em solução de ácido giberélico com posterior fratura do endocarpo. Um tratamento-testemunha, representado por pirênios não submetidos a tratamento pré-germinativo, foi acrescentado para fins de comparação. Os pirênios dos três clones, com grande frequência, contêm mais de uma semente. A presença de pirênios desprovidos de sementes foi de apenas 1% nos clones Cristo e Santarém 2 e de 4% no clone Tocantins 1. Os diásporos do clone Cristo apresentaram maior massa e maiores dimensões. Em termos de número médio de sementes por pirênio, observaram-se valores semelhante nos clones Cristo (1,7) e Santarém 2 (1,8), enquanto esse valor foi menor no clone Tocantins 1 (1,3). Os três clones apresentaram endocarpo com espessura semelhante. Os tratamentos pré-germinativos proporcionaram aumentos na porcentagem de germinação e reduções no tempo médio de germinação, com respostas mais expressivas quando os pirênios foram previamente embebidos em solução de ácido giberélico ou em água e, posteriormente, submetidos à fratura do endocarpo.

Refractory subretinal fluid in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab: visual acuity outcome.

PURPOSE: To investigate the functional outcome of eyes with neovascular AMD (nAMD) and subretinal fluid (SRF) refractory to treatment with ranibizumab. METHODS: Retrospective chart review of consecutive treatment-refractory SRF in nAMD despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, location of the refractory SRF, mean visual acuity (VA) change, number of injections, and timepoint of first complete disappearance of SRF. RESULTS: Forty-five eyes in 44 patients (mean age of 76 years) were included. The mean follow-up was 32.4 months (range 12-73 months). The mean number of injections was 11.6 in the first year and 27.5 over follow-up. The refractory SRF was located subfoveally in 66.7 %. In 12 eyes (26.7 %), complete absorption of SRF was found after a mean of 22.6 months (range, 13-41 months). Mean VA increased by 10.4, 8.2, and 8.6 letters by month 12, 24, and 36, respectively. CONCLUSIONS: Neovascular AMD with SRF refractory to monthly retreatment with ranibizumab may still allow good and maintained visual improvement, even if the fluid is located subfoveally. SRF may progressively absorb under continuous monthly treatment. The necessity to treat refractory SRF with monthly injections could be questioned and would need future investigations.

GROWTH AND NUTRITION OF CACAO SEEDLINGS INFLUENCED BY ZINC APLICATION IN SOIL

ABSTRACT Levels of Zn in tropical soils profoundly influences growth and nutrition of tree crops. Research was undertaken to assess the effect of soil Zn on growth and nutrition of clonal cacao tree seedlings of PH 16. Three acidic Oxisol soils differing in texture were used with nine doses of Zn (0, 1, 2, 4, 8, 16, 32, 48, and 64 mg dm-3). Rooted clonal seedlings were grown in plastic pot with 11 dm-3 of the soils at varying Zn levels for 240 days. At harvest growth (dry matter mass of leaves, stems, shoots, roots, and total) and nutrient concentrations were determined. The clonal cacao seedlings showed differences for production of dry matter mass and foliar nutrient concentrations for P, K, Ca, Mg, Mn, Fe, Zn, and Cu. There was Zn toxicity in all soils.

Soft tissue artifact distribution on lower limbs during treadmill gait: Influence of skin markers' location on cluster design.

Segment poses and joint kinematics estimated from skin markers are highly affected by soft tissue artifact (STA) and its rigid motion component (STARM). While four marker-clusters could decrease the STA non-rigid motion during gait activity, other data, such as marker location or STARM patterns, would be crucial to compensate for STA in clinical gait analysis. The present study proposed 1) to devise a comprehensive average map illustrating the spatial distribution of STA for the lower limb during treadmill gait and 2) to analyze STARM from four marker-clusters assigned to areas extracted from spatial distribution. All experiments were realized using a stereophotogrammetric system to track the skin markers and a bi-plane fluoroscopic system to track the knee prosthesis. Computation of the spatial distribution of STA was realized on 19 subjects using 80 markers apposed on the lower limb. Three different areas were extracted from the distribution map of the thigh. The marker displacement reached a maximum of 24.9mm and 15.3mm in the proximal areas of thigh and shank, respectively. STARM was larger on thigh than the shank with RMS error in cluster orientations between 1.2° and 8.1°. The translation RMS errors were also large (3.0mm to 16.2mm). No marker-cluster correctly compensated for STARM. However, the coefficient of multiple correlations exhibited excellent scores between skin and bone kinematics, as well as for STARM between subjects. These correlations highlight dependencies between STARM and the kinematic components. This study provides new insights for modeling STARM for gait activity.

Fontes utilizadas pelas mulheres para aquisição de conhecimentos sobre câncer de mama

OBJETIVO: Identificar as principais fontes utilizadas pelas mulheres para adquirir informações sobre câncer de mama; determinar se existe associação entre as fontes de informação usadas e o nível de escolaridade e renda familiar; estabelecer como as mulheres avaliam seus próprios conhecimentos sobre câncer de mama (auto-avaliação); determinar se esta auto-avaliação tem efeito sobre os hábitos referidos da prática do auto-exame das mamas. MATERIAIS E MÉTODOS: Quinhentas e trinta e uma mulheres, com idade de 20 anos ou mais, foram aleatoriamente entrevistadas nas dependências de um hospital particular de Goiânia, GO. RESULTADOS: A televisão foi apontada como a principal fonte utilizada para adquirir conhecimentos sobre câncer de mama (26,5% das respostas), independentemente do grau de escolaridade ou da renda familiar. Em seguida vieram as revistas (16,8%), relacionamento interpessoal (16,2%), médicos assistentes (15,8%), jornais (12,2%), rádio (8,4%) e a internet (3,9%). O teste do chi² identificou associação entre as quatro fontes mais utilizadas para adquirir informações sobre câncer de mama e a escolaridade/renda familiar. CONCLUSÃO: A televisão foi apontada, pelas entrevistadas, a fonte mais utilizada para adquirir conhecimentos sobre câncer de mama. Oitenta e três por cento das entrevistadas consideram ter conhecimentos medianos ou bons sobre câncer de mama. As mulheres que auto-atribuíram maior nível de conhecimento sobre a doença apresentaram maior propensão para realizar o auto-exame das mamas com periodicidade correta.

Dietary intake according to gender and education : a twenty-year trend in a Swiss adult population

We assessed trends in dietary intake according to gender and education using repeated cross-sectional, population-based surveys conducted between 1993 and 2012 in Geneva, Switzerland (17,263 participants, 52.0 ± 10.6 years, 48% male). In 1993-1999, higher educated men had higher monounsaturated fatty acids (MUFA), carotene and vitamin D intakes than lower educated men, and the differences decreased in 2006-2012. In 1993-1999, higher educated women had higher fiber, iron, carotene, vitamin D and alcohol intakes than lower educated women, and the differences decreased in 2006-2012. Total energy, polyunsaturated fatty acids, retinol and alcohol intakes decreased, while mono/disaccharides, MUFA and carotene intake increased in both genders. Lower educated men had stronger decreases in saturated fatty acid (SFA) and calcium intakes than higher educated men: multivariate-adjusted slope and 95% confidence interval -0.11 (-0.15; -0.06) vs. -0.03 (-0.08; 0.02) g/day/year for SFA and -5.2 (-7.8; -2.7) vs. -1.03 (-3.8; 1.8) mg/day/year for calcium, p for interaction <0.05. Higher educated women had a greater decrease in iron intake than lower educated women: -0.03 (-0.04; -0.02) vs. -0.01 (-0.02; 0.00) mg/day/year, p for interaction = 0.002. We conclude that, in Switzerland, dietary intake evolved similarly between 1993 and 2012 in both educational groups. Educational differences present in 1993 persisted in 2012.

Definição do nível da junção ureterovesical pela tomografia computadorizada

OBJETIVO: Definir o nível da implantação ureteral na bexiga através da tomografia computadorizada. MATERIAIS E MÉTODOS: Através de tomografia computadorizada da pelve com contraste endovenoso de 46 pacientes (31 homens e 15 mulheres) com idade entre 18 e 45 anos, com pelo menos um dos ureteres contrastado pelo contraste excretado, medimos as distâncias do meato ureteral até o teto acetabular e a borda superior da sínfise púbica, além do volume da bexiga. Utilizamos o teste t de Student para avaliar se houve diferenças estatísticas entre grupos. RESULTADOS: O nível da implantação ureteral na bexiga foi, em média, 10,6 ± 8,1 mm abaixo do teto acetabular e, em média, 29,7 ± 9,5 mm acima da borda superior da sínfise púbica. Nos pacientes com volume de repleção vesical menor que 200 ml e maior ou igual a 200 ml os níveis da implantação ureteral na bexiga foram, em média, 11,6 ± 7,3 mm e 10,2 ± 8,4 mm abaixo do teto acetabular (p = 0,61) e, em média, 28,3 ± 7,3 mm e 30,3 ± 10,2 mm acima da borda superior da sínfise púbica (p = 0,52), respectivamente, e nos pacientes do sexo masculino e feminino foram, em média, 11,8 ± 8,0 mm e 8,3 ± 8,0 mm abaixo do teto acetabular (p = 0,17) e, em média, 27,7 ± 9,2 mm e 33,9 ± 8,8 mm acima da borda superior da sínfise púbica (p = 0,34), respectivamente. CONCLUSÃO: Calcificações localizadas abaixo de 3 cm do teto acetabular e abaixo de 1,5 cm acima da borda superior da sínfise púbica provavelmente não representam cálculos ureterais. O grau de repleção vesical e o sexo não interferem significativamente na posição do meato ureteral.

Major congenital anomalies in babies born with Down syndrome: a EUROCAT population-based registry study.

Previous studies have shown that over 40% of babies with Down syndrome have a major cardiac anomaly and are more likely to have other major congenital anomalies. Since 2000, many countries in Europe have introduced national antenatal screening programs for Down syndrome. This study aimed to determine if the introduction of these screening programs and the subsequent termination of prenatally detected pregnancies were associated with any decline in the prevalence of additional anomalies in babies born with Down syndrome. The study sample consisted of 7,044 live births and fetal deaths with Down syndrome registered in 28 European population-based congenital anomaly registries covering seven million births during 2000-2010. Overall, 43.6% (95% CI: 42.4-44.7%) of births with Down syndrome had a cardiac anomaly and 15.0% (14.2-15.8%) had a non-cardiac anomaly. Female babies with Down syndrome were significantly more likely to have a cardiac anomaly compared to male babies (47.6% compared with 40.4%, P < 0.001) and significantly less likely to have a non-cardiac anomaly (12.9% compared with 16.7%, P < 0.001). The prevalence of cardiac and non-cardiac congenital anomalies in babies with Down syndrome has remained constant, suggesting that population screening for Down syndrome and subsequent terminations has not influenced the prevalence of specific congenital anomalies in these babies.

Avaliação do volume da placenta no primeiro trimestre de gestação por meio da ultrassonografia tridimensional utilizando o método XI VOCAL

OBJETIVO: Determinar valores de referência para o volume da placenta entre 7 e 10 semanas e 6 dias de gestação por meio da ultrassonografia tridimensional utilizando o método XI VOCAL (eXtended Imaging Virtual Organ Computer-aided Analysis). MATERIAIS E MÉTODOS: Realizou-se estudo de corte transversal com 70 gestantes normais entre 7 e 10 semanas e 6 dias. Para o cálculo de volume, utilizou-se o método XI VOCAL com delimitação de dez planos adjacentes. Foram determinadas médias, medianas, desvios-padrão, valores máximo e mínimo para o volume da placenta. Para avaliar a correlação do volume da placenta com a idade gestacional, foi criado gráfico de dispersão, sendo o ajuste realizado pelo coeficiente de determinação (R²). RESULTADOS: A média do volume da placenta variou de 4,6 cm³ (2,6-8,6 cm³) a 28,9 cm³ (11,4-66,9 cm³). O volume da placenta (VP) se mostrou altamente correlacionado com a idade gestacional (IG), sendo o melhor ajuste com a regressão exponencial [VP = exp(0,582 × IG + 0,063); R² = 0,82]. CONCLUSÃO: Valores de referência para o volume da placenta no primeiro trimestre de gestação utilizando o método XI VOCAL foram determinados.

Association between resistin levels and cardiovascular disease events in older adults: The health, aging and body composition study.

OBJECTIVE: Prospective data on the association between resistin levels and cardiovascular disease (CVD) events are sparse with conflicting results. METHODS: We studied 3044 aged 70-79 years from the Health, Aging, and Body Composition Study. CVD events were defined as coronary heart disease (CHD) or stroke events. «Hard » CHD events were defined as CHD death or myocardial infarction. We estimated hazard ratio (HR) and 95% confidence intervals (CI) according to the quartiles of serum resistin concentrations and adjusted for clinical variables, and then further adjusted for metabolic disease (body mass index, fasting plasma glucose, abdominal visceral and subcutaneous adipose tissue, leptin, adiponectin, insulin) and inflammation (C-reactive protein, interleukin-6, tumor necrosis factors-α). RESULTS: During a median follow-up of 10.1 years, 559 patients had « hard » CHD events, 884 CHD events and 1106 CVD Events. Unadjusted incidence rate for CVD events was 36.6 (95% CI 32.1-41.1) per 1000 persons-year in the lowest quartile and 54.0 per 1000 persons-year in the highest quartile (95% CI 48.2-59.8, P for trend < 0.001). In the multivariate models adjusted for clinical variables, HRs for the highest vs. lowest quartile of resistin was 1.52 (95% CI 1.20-1.93, P < 0.001) for « Hard » CHD events, 1.41 (95% CI 1.16-1.70, P = 0.001) for CHD events and 1.35 (95% CI 1.14-1.59, P = 0.002) for CVD events. Further adjustment for metabolic disease slightly reduced the associations while adjustment for inflammation markedly reduced the associations. CONCLUSIONS: In older adults, higher resistin levels are associated with CVD events independently of clinical risk factors and metabolic disease markers, but markedly attenuated by inflammation.

Use of the nutritional risk score by surgeons and nutritionists.

BACKGROUND: The Nutritional Risk Score (NRS) is a validated tool to identify patients who should benefit of nutritional interventions. Nutritional screening however has not yet been widely adopted by surgeons. Furthermore, the question about reliability of nutritional assessment performed by surgeons is still unanswered. METHODS: Data was obtained from a recent randomised trial including 146 patients with an NRS ≥3 as assessed by the surgeons. Additional detailed nutritional assessment was performed for all patients by nutritional specialists and entered prospectively in a dedicated database. In this retrospective, surgeons' scoring of NRS and its components was compared to the assessment by nutritionists (considered as gold standard). RESULTS: Prospective NRS scores by surgeons and nutritionists were available for 141 patients (97%). Surgeons calculated a NRS of 7, 6, 5, 4 and 3 in 2, 8, 38, 21 and 72 patients respectively. Nutritionists calculated a NRS of 6, 5, 4, 3 and 2 in 8, 26, 47, 57, 3 patients, respectively. Surgeons' assessment was entirely correct in 56 patients (40%), while at least the final score was consistent in 63 patients (45%). Surgeons overrated the NRS in 21% of patients and underestimated the score in 29%. Evaluation of the nutritional status showed most of the discrepancies (54%). CONCLUSION: Surgeon's assessment of nutritional status is modest at best. Close collaboration with nutritional specialists should be recommended in order to avoid misdiagnosis and under-treatment of patients at nutritional risk.

Avaluació de l'efecte causat sobre els valors de potència entre un protocol d'entrenament de càrregues baixes i un amb càrregues submàximes

L’objectiu d’aquest estudi és comparar els efectes que produeixen un protocol d’entrenament orientat amb càrregues lleugeres (40%-60% 1RM) i un protocol d’entrenament amb càrregues altes submàximes (90% 1RM), sobre els nivells de potència muscular. L’estudi ha analitzat a 12 futbolistes masculins pertanyents al mateix equip (22,1 ± 2,9 anys, 72,2 ± 6, 8 kg, 1,77 ± 0,15 m). Els exercicis analitzats foren el ½ squat i el press banca. També es va utilitzar un grup control. Els resultats ens van mostrar que el grup d’entrenament amb càrregues lleugeres va obtenir unes millores més considerables sobre els valors de potència (W) en 40% i 60% 1RM i per altre banda en el grup d’entrenament amb càrregues submàximes es van produir uns increments de potència més alts en càrregues altes (80% 1RM). Els resultats referents a la velocitat mitjana (m/s), es van produir de manera més considerable en el grup que va realitzar el treball amb càrregues lleugeres, en totes les intensitats analitzades.