Le carcinome hépatocellulaire: une approche multidisciplinaire [Hepatocellular carcinoma: a multidisciplinary approach]

The treatment of the hepatocellular carcinoma (HCC) is multidisciplinary. Hepatic transplantation offers the best chances of survival for patients with hepatic cirrhosis and HCC. However the indications for transplantation are limited. For patients that do not qualify for liver transplantation, surgical excision and percutaneous ablative treatment can also be curative. Five years survival then reaches 50%. The choice of treatment is based upon the patient's clinical state, the hepatic function and the cancer clinical stage. Follow-up is crucial as recurrences can be treated by following similar algorithms. The efficacy of oncological adjuvant and neoadjuvant treatment is not yet proved.

Formas de adubação e doses de uréia para mudas clonais de cacau cultivadas em substrato

O N é o nutriente mais demandado pelas plantas. Contudo, para produção de mudas enraizadas de cacaueiro em substratos e sob irrigação freqüente não existem estudos de calibração de adubação nitrogenada. Os objetivos deste trabalho foram comparar a eficiência das adubações no substrato e foliar com uréia para mudas clonais de cacau e definir doses recomendáveis e nível crítico foliar de N. O experimento foi instalado em viveiro de produção de mudas do Instituto Biofábrica de Cacau, em Ilhéus, Bahia, em julho de 2006, envolvendo 10 tratamentos (duas formas de adubação, combinadas com cinco doses de uréia), em blocos casualizados, com quatro repetições. A parcela útil constituiu-se de 12 mudas clonais de cacaueiro cultivadas em tubetes, contendo 288 cm³ de substrato (50 % de fibra de coco e 50 % de Plantmax®). O substrato foi corrigido com 3,20 kg m-3 de calcário e adubado com 2,68 kg m-3 de superfosfato simples. Os tratamentos foram aplicados entre o 82º até o 138º dia, com as seguintes doses semanais de N: 0, 20, 40, 60 e 80 mg dm-3 via substrato e 0,0; 2,25; 4,5; 9,0; e 13,5 g L-1 via foliar. Em todos os tratamentos, fez-se a adubação complementar com P, K, S, Zn e B via substrato. Aos 145 dias, as plantas foram colhidas, sendo avaliados: diâmetro da haste principal, altura, área foliar, matéria seca da parte aérea (MSPA), teor de nutrientes na folha diagnóstica e conteúdo de nutrientes na parte aérea. As variáveis biométricas e nutricionais responderam aos tratamentos. A adubação via substrato proporcionou produção máxima superior à adubação foliar, para MSPA, altura e área foliar. As doses recomendáveis de N, calculadas para obtenção de 99 % da produção máxima, variaram de acordo com a variável biométrica de 43 a 76 mg dm-3 para adubação via substrato e de 9,1 a 11,7 g L-1 para adubação foliar. O nível crítico foliar de N, para obtenção de 99 % da produção máxima da MSPA, foi de 23,1 g kg-1.

High-intensity intermittent training in hypoxia: a double-blinded, placebo-controlled field study in youth football players.

High-intensity intermittent training in hypoxia: A double-blinded, placebo-controlled field study in youth football players. J Strength Cond Res 29(1): 226-237, 2015-This study examined the effects of 5 weeks (∼60 minutes per training, 2 d·wk) of run-based high-intensity repeated-sprint ability (RSA) and explosive strength/agility/sprint training in either normobaric hypoxia repeated sprints in hypoxia (RSH; inspired oxygen fraction [FIO2] = 14.3%) or repeated sprints in normoxia (RSN; FIO2 = 21.0%) on physical performance in 16 highly trained, under-18 male footballers. For both RSH (n = 8) and RSN (n = 8) groups, lower-limb explosive power, sprinting (10-40 m) times, maximal aerobic speed, repeated-sprint (10 × 30 m, 30-s rest) and repeated-agility (RA) (6 × 20 m, 30-s rest) abilities were evaluated in normoxia before and after supervised training. Lower-limb explosive power (+6.5 ± 1.9% vs. +5.0 ± 7.6% for RSH and RSN, respectively; both p < 0.001) and performance during maximal sprinting increased (from -6.6 ± 2.2% vs. -4.3 ± 2.6% at 10 m to -1.7 ± 1.7% vs. -1.3 ± 2.3% at 40 m for RSH and RSN, respectively; p values ranging from <0.05 to <0.01) to a similar extent in RSH and RSN. Both groups improved best (-3.0 ± 1.7% vs. -2.3 ± 1.8%; both p ≤ 0.05) and mean (-3.2 ± 1.7%, p < 0.01 vs. -1.9 ± 2.6%, p ≤ 0.05 for RSH and RSN, respectively) repeated-sprint times, whereas sprint decrement did not change. Significant interactions effects (p ≤ 0.05) between condition and time were found for RA ability-related parameters with very likely greater gains (p ≤ 0.05) for RSH than RSN (initial sprint: 4.4 ± 1.9% vs. 2.0 ± 1.7% and cumulated times: 4.3 ± 0.6% vs. 2.4 ± 1.7%). Maximal aerobic speed remained unchanged throughout the protocol. In youth highly trained football players, the addition of 10 repeated-sprint training sessions performed in hypoxia vs. normoxia to their regular football practice over a 5-week in-season period was more efficient at enhancing RA ability (including direction changes), whereas it had no additional effect on improvements in lower-limb explosive power, maximal sprinting, and RSA performance.

Evolution of glucose induced thermogenesis in obese subjects with and without diabetes: a six-year follow-up study.

The thermogenic response to a 100 g oral glucose load was measured prospectively (by indirect calorimetry) in three groups of obese subjects: (1) normal glucose tolerance (n = 12, initial weight 86.4 +/- 3.9 kg, BMI 30.4 +/- 1.1 kg/m2; (2) impaired glucose tolerance (n = 8, initial weight 105.3 +/- 7.6 kg, body mass index (BMI) 37.6 +/- 2.9 kg/m2; (3) diabetes (n = 12), initial weight 102.1 +/- 5.3 kg, BMI 36.2 +/- 2.0 kg/m2). The thermogenic response to glucose averaged 6.8 +/- 1.1 and 7.0 +/- 1.0 per cent, in the two non-diabetic obese groups respectively, and was significantly lower in the obese diabetic group (3.1 +/- 0.8 per cent). With the evolution of obesity (i.e. 6 years later), the glucose-induced thermogenesis (GIT) was significantly reduced in the non-diabetic groups (P less than 0.05) to 4.1 +/- 0.8 and 3.0 +/- 1.1 per cent respectively, and was still blunted in the diabetic group (2.1 +/- 0.7 per cent). The decrease in GIT was accompanied by a reduction in glucose tolerance and insulin response with no change in fasting plasma insulin. These effects were observed despite the fact that the body weight of the subject did not change significantly over the 6-year period. It is concluded that the decrease in GIT which accompanies the worsening of glucose tolerance and the occurrence of diabetes is a mechanism which may contribute to maintain the obesity state by a reduction of energy expenditure.

DSM-IV and DSM-5 alcohol use disorder among young Swiss men.

BACKGROUND AND AIMS: Previous studies suggest that the new DSM-5 criteria for alcohol use disorder (AUD) will increase the apparent prevalence of AUD. This study estimates the 12-month prevalence of AUD using both DSM-IV and DSM-5 criteria and compares the characteristics of men in a high risk sample who meet both, only one and neither sets of diagnostic criteria. DESIGN, SETTING AND PARTICIPANTS: 5943 Swiss men aged 18-25 years who participated in the Cohort Study on Substance Use Risk Factors (C-SURF), a population-based cohort study recruited from three of the six military recruitment centres in Switzerland (response rate = 79.2%). MEASUREMENTS: DSM-IV and DSM-5 criteria, alcohol use patterns, and other substance use were assessed. FINDINGS: Approximately 31.7% (30.5-32.8) of individuals met DSM-5 AUD criteria [21.2% mild (20.1-22.2); 10.5% moderate/severe (9.7-11.3)], which was less than the total rate when DSM-IV criteria for alcohol abuse (AA) and alcohol dependence (AD) were combined [36.8% overall (35.5-37.9); 26.6% AA (25.4-27.7); 10.2% AD (9.4-10.9)]. Of 2479 respondents meeting criteria for either diagnoses, 1585 (63.9%) met criteria for both. For those meeting DSM-IV criteria only (n = 598, 24.1%), hazardous use was most prevalent, whereas the criteria larger/longer use than intended and tolerance to alcohol were most prevalent for respondents meeting DSM-5 criteria only (n = 296, 11.9%). Two in five DSM-IV alcohol abuse cases and one-third of DSM-5 mild AUD individuals fulfilled the diagnostic criteria due to the hazardous use criterion. The addition of the craving and excluding of legal criterion, respectively, did not affect estimated AUD prevalence. CONCLUSIONS: In a high-risk sample of young Swiss males, prevalence of alcohol use disorder as diagnosed by DSM-5 was slightly lower than prevalence of DSM-IV diagnosis of dependence plus abuse; 63.9% of those who met either criterion met criteria for both.

Crescimento e nutrição de clone de eucalipto em resposta à aplicação de concentrações de c-ácido húmico

Os efeitos das substâncias húmicas nas propriedades dos solos são conhecidos, porém poucos são os estudos que avaliam os efeitos desses materiais nas plantas; assim, dependendo da concentração e da natureza química das moléculas húmicas aplicadas, pode haver maior expansão radicular, incremento na absorção de nutrientes e maior crescimento das culturas. Com o objetivo de avaliar os efeitos de concentrações de C-ácido húmico na nutrição e no crescimento de mudas de eucalipto, foi realizado um experimento em solução nutritiva, em casa de vegetação. Os tratamentos constituíram-se de duas fontes de ácidos húmicos (material húmico - MH e ácido húmico p.a. - AH p.a.), sendo cada fonte adicionada na solução nutritiva nas seguintes concentrações de C-ácido húmico: 0, 10, 30 e 150 mg L-1. Outros tratamentos foram também testados, utilizando-se a fonte AH p.a. nas concentrações de 0, 10, 30 e 150 mg L-1 C-ácido húmico, acrescidas de 21 mg L-1 de ácido cítrico e 9 mg L-1 de ácido oxálico. Foram analisados a condutividade eletrolítica na solução nutritiva, diâmetro do caule e altura das plantas, matéria seca de caule, de folhas, da parte aérea, da raiz e total, relação matéria seca de raiz:parte aérea, acúmulo de nutrientes no caule e nas folhas. A altura e o diâmetro de caule diminuíram linearmente com a aplicação de concentrações de C-ácido húmico da fonte AH p.a. A utilização do MH, em baixas concentrações de C-ácido húmico (0,07-4,3 mg L-1), propiciou a máxima produção de matéria seca de raiz, caule, folha e total. O maior acúmulo de alguns nutrientes (principalmente N, P e B) resultou, em alguns tratamentos, em reduzidos incrementos (2,4 a 9,3 %) nas produções de matéria seca de raiz, folha, caule e total; assim, não é aconselhável, em solução nutritiva, a aplicação das fontes de ácidos húmicos utilizadas neste estudo para o cultivo de mudas de eucalipto.

Year-round poultry litter decomposition and N, P, K and Ca release

Poultry litter is an important nutrient source in agriculture, although little information is available regarding its decomposition rate and nutrient release. To evaluate these processes, poultry litter (PL) was applied to the soil to supply 100, 200 and 300 kg ha-1 N contained in 4,953, 9,907 and 14,860 kg ha-1 PL, respectively. The litter bag technique was used to monitor the process of decomposition and nutrient release from the litter. These bags were left on the soil surface and collected periodically (after 15, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, and 365 days). The dry matter (DM) loss was highest (35 %) after the first 30 days of field incubation. The highest nutrient release occurred in the first 60 days on the field, when 40, 34, 91, and 39 %, respectively, of N, P, K, and Ca of the initial PL dry matter (4,860 kg ha-1) was already released to the soil. In absolute terms, these percentages represent 40, 23, 134, and 69 kg ha-1 of N, P, K, and Ca and these values doubled and tripled as the PL fertilization rates increased to 9,907 and 14,860 kg ha-1, respectively. After one year of field incubation, the residual contents in the litter were 27, 15, 18 and 30 % of the initial DM , and N, P and Ca, respectively. The release rate of K was the fastest and 91 % of the K had been released from the PL after 30 days of field incubation.

Estimating dormant and active hematopoietic stem cell kinetics through extensive modeling of bromodeoxyuridine label-retaining cell dynamics.

Bone marrow hematopoietic stem cells (HSCs) are responsible for both lifelong daily maintenance of all blood cells and for repair after cell loss. Until recently the cellular mechanisms by which HSCs accomplish these two very different tasks remained an open question. Biological evidence has now been found for the existence of two related mouse HSC populations. First, a dormant HSC (d-HSC) population which harbors the highest self-renewal potential of all blood cells but is only induced into active self-renewal in response to hematopoietic stress. And second, an active HSC (a-HSC) subset that by and large produces the progenitors and mature cells required for maintenance of day-to-day hematopoiesis. Here we present computational analyses further supporting the d-HSC concept through extensive modeling of experimental DNA label-retaining cell (LRC) data. Our conclusion that the presence of a slowly dividing subpopulation of HSCs is the most likely explanation (amongst the various possible causes including stochastic cellular variation) of the observed long term Bromodeoxyuridine (BrdU) retention, is confirmed by the deterministic and stochastic models presented here. Moreover, modeling both HSC BrdU uptake and dilution in three stages and careful treatment of the BrdU detection sensitivity permitted improved estimates of HSC turnover rates. This analysis predicts that d-HSCs cycle about once every 149-193 days and a-HSCs about once every 28-36 days. We further predict that, using LRC assays, a 75%-92.5% purification of d-HSCs can be achieved after 59-130 days of chase. Interestingly, the d-HSC proportion is now estimated to be around 30-45% of total HSCs - more than twice that of our previous estimate.

Axillary Sentinel Lymph Node Biopsy for Breast Cancer and Melanoma Patients after Previous Axillary Surgery: A Systematic Review

Objective: Sentinel lymph node biopsy (SLNB) is a validated staging technique for breast carcinoma. Some women are exposed to have a second SLNB due to breast cancer recurrence or a second neoplasia (breast or other). Due to modi- fied anatomy, it has been claimed that previous axillary surgery represents a contra-indication to SLNB. Our objective was to analyse the literature to assess if a second SLNB is to be recommended or not. Methods: For the present study, we performed a review of all published data during the last 10 years on patients with previous axilla surgery and second SLNB. Results: Our analysis shows that second SLNB is feasible in 70%. Extra-axillary SNs rate (31%) was higher after radical lymph node dissection (ALND) (60% - 84%) than after SLNB alone (14% - 65%). Follow-up and com- plementary ALND following negative and positive second SLNB shows that it is a reliable procedure. Conclusion: The review of literature confirms that SLNB is feasible after previous axillary dissection. Triple technique for SN mapping is the best examination to highlight modified lymphatic anatomy and shows definitively where SLNB must be per- formed. Surgery may be more demanding as patients may have more frequently extra-axillary SN only, like internal mammary nodes. ALND can be avoided when second SLNB harvests negative SNs. These conclusions should however be taken with caution because of the heterogeneity of publications regarding SLNB and surgical technique.

[Illustrations de Le Père Goriot; scènes de la vie parisienne] / Lynch, dess. ; E. Abot, grav. ; Honoré de Balzac, aut. du texte

Comprend : [Pl. en reg. p.46 :] Goriot mangeait machinalement. Jamais il n'avait semblé plus absorbé. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.78 :] "Madame, je ne suis encore qu'un pauvre diable d'étudiant..." dit Eugène à la duchesse. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.107 :] "Expliquons-nous..." dit Vautrin en prenant Eugène par le bras. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.133 :] Le marquis présenta l'étudiant à Mme Nucingen... [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.146 :] En sortant du cours Cuvier, Bianchon aperçut Mlle Michonneau et Poiret causant avec un monsieur qu'il sembla reconaître... [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.151 :] "Suis-je à votre goût?..." dit Mme de Nucingen en se levant et montrant sa robe de cachemire blanc à dessins. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.229 :] Mme de Nucingen se jeta dans les bras de son père, et couvrit de baisers son visage épanoui... [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.254 :] Le Père Goriot s'élança entre ses deux filles pour les embpêcher de continuer cet échange de reproches. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.272 :] "Je tremblais que vous ne vinssiez pas..." dit Mme de Beauséant à Rastignac. [Cote : Res p Y2 159/Microfilm R 122341] ; [Pl. en reg. p.300 :] "Mon père est mort!... " cria la comtesse en tombant évanouie. [Cote : Res p Y2 159/Microfilm R 122341]

Safety and effectiveness of amphotericin B deoxycholate for the treatment of visceral leishmaniasis in Uganda

Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb-V). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in-hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) =2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI=1.4%-7.9%) among the 161 patients treated with Sb-V (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI= 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI=0.1%-4.4%) of the patients treated with Sb-V (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.

Visualization of RNA polymerase II ternary transcription complexes formed in vitro on a Xenopus laevis vitellogenin gene.

Stable ternary transcription complexes assembled in vitro, using a HeLa whole-cell extract, have been isolated and visualized by electron microscopy. The formation of these stable complexes on the DNA fragment used as template, the 5' end region of the Xenopus laevis vitellogenin gene B2, depends on factors present in the whole-cell extract, RNA polymerase II and at least two nucleotides. Interestingly, bending in the DNA fragment was frequently observed at the binding site of RNA polymerase II. Dinucleotides that can prime initiation within a short sequence of approximately 10 contiguous nucleotides centered around the initiation site used in vivo, also favour the formation of stable complexes. In addition, pre-initiation complexes were isolated and it was shown that factors in the extract involved in their formation are more abundant than the RNA polymerase II molecules available for binding. The possible implication of this observation relative to the in vivo situation is discussed.

Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species.

Novel macrocyclic amidinourea derivatives 11, 18, and 25 were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds 11 and 18 were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds 25 were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole.

Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease.

BACKGROUND: Direct noninvasive visualization of the coronary vessel wall may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. We sought to evaluate high-resolution black-blood 3D cardiovascular magnetic resonance (CMR) imaging for in vivo visualization of the proximal coronary artery vessel wall. METHODS AND RESULTS: Twelve adult subjects, including 6 clinically healthy subjects and 6 patients with nonsignificant coronary artery disease (10% to 50% x-ray angiographic diameter reduction) were studied with the use of a commercial 1.5 Tesla CMR scanner. Free-breathing 3D coronary vessel wall imaging was performed along the major axis of the right coronary artery with isotropic spatial resolution (1.0x1.0x1.0 mm(3)) with the use of a black-blood spiral image acquisition. The proximal vessel wall thickness and luminal diameter were objectively determined with an automated edge detection tool. The 3D CMR vessel wall scans allowed for visualization of the contiguous proximal right coronary artery in all subjects. Both mean vessel wall thickness (1.7+/-0.3 versus 1.0+/-0.2 mm) and wall area (25.4+/-6.9 versus 11.5+/-5.2 mm(2)) were significantly increased in the patients compared with the healthy subjects (both P<0.01). The lumen diameter (3.6+/-0.7 versus 3.4+/-0.5 mm, P=0.47) and lumen area (8.9+/-3.4 versus 7.9+/-3.5 mm(2), P=0.47) were similar in both groups. CONCLUSIONS: Free-breathing 3D black-blood coronary CMR with isotropic resolution identified an increased coronary vessel wall thickness with preservation of lumen size in patients with nonsignificant coronary artery disease, consistent with a "Glagov-type" outward arterial remodeling. This novel approach has the potential to quantify subclinical disease.

Antihypertensive drug treatment changes in the general population: the CoLaus study.

BACKGROUND: Changes in antihypertensive drug treatment are paramount in the adequate management of patients with hypertension, still, there is little information regarding changes in antihypertensive drug treatment in Switzerland. Our aim was to assess those changes and associated factors in a population-based, prospective study. METHODS: Data from the population-based, CoLaus study, conducted among subjects initially aged 35-75 years and living in Lausanne, Switzerland. 772 hypertensive subjects (371 women) were followed for a median of 5.4 years. Data Subjects were defined as continuers (no change), switchers (one antihypertensive class replaced by another), combiners (one antihypertensive class added) and discontinuers (stopped treatment). The distribution and the factors associated with changes in antihypertensive drug treatment were assessed. RESULTS: During the study period, the prescription of diuretics decreased and of ARBs increased: at baseline, diuretics were taken by 46.9% of patients; angiotensin receptor blockers (ARB) by 44.7%, angiotensin converting enzyme inhibitors (ACEI) by 28.8%, beta-blockers (BB) by 28.0%, calcium channel blockers (CCB) by 18.9% and other antihypertensive drugs by 0.3%. At follow-up (approximately 5 years later), their corresponding percentages were 42.8%, 51.7%, 25.5%, 33.0% 20.7% and 1.0%. Among all participants, 54.4% (95% confidence interval: 50.8-58.0) were continuers, 26.9% (23.8-30.2) combiners, 12.7% (10.4-15.3) switchers and 6.0% (4.4-7.9) discontinuers. Combiners had higher systolic blood pressure values at baseline than the other groups (p < 0.05). Almost one third (30.6%) of switchers and 29.3% of combiners improved their blood pressure status at follow-up, versus 18.8% of continuers and 8.7% of discontinuers (p < 0.001). Conversely, almost one third (28.3%) of discontinuers became hypertensive (systolic ≥140 mm Hg or diastolic ≥90 mm Hg), vs. 22.1% of continuers, 16.3% of switchers and 11.5% of combiners (p < 0.001). Multivariate analysis showed baseline uncontrolled hypertension, ARBs, drug regimen (monotherapy/polytherapy) and overweight/obesity to be associated with changes in antihypertensive therapy. CONCLUSION: In Switzerland, ARBs have replaced diuretics as the most commonly prescribed antihypertensive drug. Uncontrolled hypertension, ARBs, drug regimen (monotherapy or polytherapy) and overweight/obesity are associated with changes in antihypertensive treatment.