A role for Yin Yang-1 (YY1) in the assembly of snRNA transcription complexes.

The RNA polymerase (pol) II and III human small nuclear RNA (snRNA) genes have very similar promoters and recruit a number of common factors. In particular, both types of promoters utilize the small nuclear RNA activating protein complex (SNAP(c)) and the TATA box binding protein (TBP) for basal transcription, and are activated by Oct-1. We find that SNAP(c) purified from cell lines expressing tagged SNAP(c) subunits is associated with Yin Yang-1 (YY1), a factor implicated in both activation and repression of transcription. Recombinant YY1 accelerates the binding of SNAP(c) to the proximal sequence element, its target within snRNA promoters. Moreover, it enhances the formation of a complex on the pol III U6 snRNA promoter containing all the factors (SNAP(c), TBP, TFIIB-related factor 2 (Brf2), and B double prime 1 (Bdp1)) that are sufficient to direct in vitro U6 transcription when complemented with purified pol III, as well as that of a subcomplex containing TBP, Brf2, and Bdp1. YY1 is found on both the RNA polymerase II U1 and the RNA polymerase III U6 promoters as determined by chromatin immunoprecipitations. Thus, YY1 represents a new factor that participates in transcription complexes formed on both pol II and III promoters.

TCR signaling requirements for activating T cells and for generating memory.

Over the last two decades the molecular and cellular mechanisms underlying T cell activation, expansion, differentiation, and memory formation have been intensively investigated. These studies revealed that the generation of memory T cells is critically impacted by a number of factors, including the magnitude of the inflammatory response and cytokine production, the type of dendritic cell [DC] that presents the pathogen derived antigen, their maturation status, and the concomitant provision of costimulation. Nevertheless, the primary stimulus leading to T cell activation is generated through the T cell receptor [TCR] following its engagement with a peptide MHC ligand [pMHC]. The purpose of this review is to highlight classical and recent findings on how antigen recognition, the degree of TCR stimulation, and intracellular signal transduction pathways impact the formation of effector and memory T cells.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes.

Hinassa 2.8.1943

Kirje

El impacto de los servicios sanitarios sobre la salud

This paper reviews what has increased medical-care spending bought in terms of health benefitswith longitudinal data from the U.S and, more limited, from Spain. Health services contributionto health has been positive in average, especially during the last 50 years for the U.S andthe last 30 years for Spain. This contribution differs among countries and is much greater forsome diseases (cardiovascular) than for others (cancer). Benefits from health care interventionscan be valued on basis on the social willin gness to pay, observed or declared on the process ofestablishing health policy priorities. 30.000 euros per Quality Adjusted Life Year could providean efficiency threshold for financing publicly health services in Spain: Consensus andlegitimacy of the political process of establishing health priorities becomes, however, moreimportant than any approximate number. Attention is paid finally to bridging the gap betweenefficacy (the possibilities given by innovation and resources devoted to health care) andeffectiveness (the distance to the frontier) of the everyday working of a health system with itsinappropriate care and limited application of the existing knowledge.

Vitamin C requirements in parenteral nutrition.

Some biochemical functions of vitamin C make it an essential component of parenteral nutrition (PN) and an important therapeutic supplement in other acute conditions. Ascorbic acid is a strong aqueous antioxidant and is a cofactor for several enzymes. The average body pool of vitamin C is 1.5 g, of which 3%-4% (40-60 mg) is used daily. Steady state is maintained with 60 mg/d in nonsmokers and 140 mg/d in smokers. Shocked surgical, trauma, and septic patients have a drastic reduction of circulating plasma ascorbate concentrations. These low concentrations require 3-g doses/d to restore normal plasma ascorbate concentrations, questioning the recommended PN dose of 100 mg/d. Determination of intravenous requirements is usually based on plasma concentrations, which are altered during the inflammatory response. There is no clear indicator of deficiency: serum or plasma ascorbate concentrations <0.3 mg/dL (20 micromol/L) indicates inadequate vitamin C status. On the basis of available pharmacokinetic data the 100 mg/d dose for patients receiving home PN and 200 mg/d for stable adult patients receiving PN are adequate, but requirements have been shown to be higher in perioperative, trauma, burn, and critically ill patients, paralleling oxidative stress. One recommendation cannot fit all categories of patients. Large vitamin C supplements may be considered in severe critical illness, major trauma, and burns because of increased requirements resulting from oxidative stress and wound healing. Future research should distinguish therapeutic use of high-dose ascorbic acid antioxidant therapy from nutritional PN requirements.

ANSA - Relatório Estatistico

Cereais: Da análise realizada nos dados do 4º trimestre de 2012, o abastecimento no conjunto dos cereais, aponta um ligeiro declíneo no stock final e stock médio, e aumentos na importação, e a disponibilidade média. ■ Neste mesmo periodo a disponibilidade total do conjunto dos cereais é de 32.296 tons, sendo 16.241 tons referente ao stock inicial, e 16.055 tons referente as importações do mesmo conjunto. A disponibilidade média mensal no trimestre é de 20.803 tons e cobre largamente as necessidades previstas do consumo médio mensal aparente que é de 7.056 tons por mês. Relativamente ao trimestre anterior registou-se um decréscimo das disponibilidades médias mensais do conjunto dos cereais da ordem do 18,8%. Este decréscimo teve maior destaque no arroz pela grande descida num valor de 32,7% no trimestre ■ O conjunto dos cereais, no final do 4º trimestre de 2012, totalizaram um stock de 16.241 tons, que vai coresponder um prazo de cobertura de 4,6 meses. Regista-se uma variação absoluta negativa entre o stock inicial e final no 4º trimestre de 2012 na ordem de 760 tons, no conjunto dos cereais, esta descida registou, no milho e no trigo, que apresentaram uma redução 4.412 tons e 1.352 tons respectivamente. ■ No 4º trimestre de 2012, a importação dos grandes operadores no conjunto dos cereais é de 16.055 tons, sendo no milho com 8.686 tons que representa a maior quantidade importada no ano 2012. Em relação ao trimestre anterior houve um aumento de 6.008 tons no conjunto dos cereais. ■ O consumo aparente do conjunto dos cereais neste periodo totalizou-se 21.168 tons, o arroz contribui com 7.171 tons para o total (33,9%) seguido do trigo com 5.842 tons do total (27,6%). Comparado com o trimestre anterior, registou-se uma queda de 1,0% no consumo dos cereais. O grau de utilização média mensal do trimestre das disponibilidades dos grandes operadores é de 33,9% contra o valor médio mensal de 28,2% verificado no trimestre anterior. ■ A distribuição inter-ilhas do conjunto dos cereais totalizou num valor de 7.927 tons, no qual 1.118 tons de milho, 1.798 tons do arroz e 5.012 tons da farinha de trigo ■ Neste trimestre, o preço do conjunto dos cereais teve ligeiros declíneos, com uma baixa no milho de 5,1% e no arroz de 1,7%. Na farinha de trigo registou-se um aumento de 3,2%. Açúcar: Com base nos dados do 4º trimestre de 2012, considera-se que o abastecimento do açúcar segue uma tendência favorável, com aumentos dos stoks, da importação e das disponibilidades médias . ■ Neste trimestre a disponibilidade total do açúcar é de 5.071 tons, sendo 2.618 tons do stock inicial e 2.453 tons da importação e cobre largamente às necessidades do consumo aparente que é de 2.095 tons. A disponibilidade média mensal do açúcar no trimestre é de 3.378 tons e em relação ao trimestre anterior verifica-se uma baixa de 4,5%. ■ No final do trimestre o stock do açúcar é de 2.976 tons e o prazo de cobertura é de 3,4 meses. A variação entre o stock inicial e final é de 358 tons. ■ O grau de utilização média mensal do trimestre das disponibilidades do açúcar dos grandes operadores é de 43,9%, estima-se que o consumo aparente médio é de 698 tons mensal. ■ Neste trimestre, a distribuição inter-ilhas total do açúcar é de 484 tons. Esta quantidade foi distribuida para todas as ilhas. ■ O preço de açúcar teve redução de 1,7% em relação ao trimestre anterior, e continua apontar uma diminuição para o próximo trimestre.

Hki 1/8 1943

Kirje 1.8.1943

Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration.

PURPOSE: To investigate the rhythm and predictability of the need for retreatment with intravitreal injections of ranibizumab for neovascular age-related macular degeneration (nAMD). METHODS: This prospective study enrolled 39 patients with treatment-naïve nAMD. After three loading doses of intravitreal ranibizumab, patients underwent an intensified follow-up for 12 months (initially weekly, then with stepwise increases to every 2 weeks and to monthly after each injection). Patients were retreated on an as-needed basis if any fluid or increased central retinal thickness (CRT) (>50μm) was found on spectral domain optical coherence tomography (OCT). Statistical analysis included patients who received at least two retreatments (five injections). RESULTS: A mean of 7.5 injections (range 0-12) were given between months 3 and 15. The mean visual acuity increased by 13.1 and 12.6 ETDRS letters at months 12 and 15 respectively. Two or more injection-retreatment intervals were found in 31 patients. The variability of their intra-individual intervals up to 14 weeks was small (SD 0-2.13 weeks), revealing a high regularity of the retreatment rhythm. The SD was correlated with the mean interval duration (r = 0.89, p < 0.001). The first interval was a good predictor of the following intervals (regression coefficient =0.81). One retreatment criterion was stable in 97 % of patients (cysts or subretinal fluid). CONCLUSION: The results of this study demonstrate a high intra-individual predictability of retreatment need with ranibizumab injections for nAMD. These findings may be helpful for developing individualized treatment plans for maintained suppression of disease activity with a minimum of injections and visits.

Orofacial dysfunction in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) affects orofacial function. Our aim was to evaluate certain characteristics of orofacial function in DMD and relate possible deteriorations to the age of the patients and to the diminished internal structure quality of the masseter muscle. Bite force and finger force were measured in 16 DMD patients (6-20 years old) and 16 age matched controls. The thickness and internal structure quality of the masseter muscle were evaluated ultrasonographically. We found reduced mouth opening but no signs of masticatory muscle tenderness. Bite force values were lower for DMD patients. Masseter thickness showed no significant differences between the two groups, but poorer internal muscle structure quality characterised the elder, non-walking DMD patients explaining their low bite force values. In conclusion, the masseter muscle follows the general progress of the disease. Orofacial function in DMD patients is becoming ever more important as their life expectancy increases.