Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype.

Recent evidence suggests that carpal tunnel syndrome (CTS) and brachial biceps tendon rupture (BBTR) represent red flags for ATTR cardiac amyloidosis (ATTR-CA). The prevalence of upper limb tenosynovial complications in conditions entering differential diagnosis with CA, such as HCM or Anderson-Fabry disease (AFD), and hence their predictive accuracy in this setting, still remains unresolved. OBJECTIVE: To investigate the prevalence of CTS and BBTR in a consecutive cohort of ATTR-CA patients, compared with patients with HCM or AFD and with individuals without cardiac disease history. PARTICIPANTS: Consecutive patients with a diagnosis of ATTR-CA, HCM and AFD were evaluated. A control group of consecutive patients was recruited among subjects hospitalized for noncardiac reasons and no cardiac disease history. The presence of BBTR, CTS or prior surgery related to these conditions was ascertained. RESULTS: 342 patients were prospectively enrolled, including 168 ATTR-CA (141 ATTRwt, 27 ATTRm), 81 with HCM/AFD (N = 72 and 9, respectively) and 93 controls. CTS was present in 75% ATTR-CA patients, compared with 13% and 10% of HCM/AFD and controls (P = 0.0001 for both comparisons). Bilateral CTS was present in 60% of ATTR-CA patients, while it was rare (2%) in the other groups. BBTR was present in 44% of ATTR-CA patients, 8% of controls and 1% in HCM/AFD. CONCLUSIONS: CTS and BBTR are fivefold more prevalent in ATTR-CA patients compared with cardiac patients with other hypertrophic phenotypes. Positive predictive accuracy for ATTR-CA is highest when involvement is bilateral. Upper limb assessment of patients with HCM phenotypes is a simple and effective way to raise suspicion of ATTR-CA.

Clisagri: An R package for agro-climate services.

Crop yields are affected by unfavourable/extreme weather and climate events occurring during sensitive growth stages. Understanding the risks associated with these events is essential to adapt agro-management decisions and reduce losses. For this purpose, we propose a targeted climate service integrating a dynamic crop phenology model with an approach based on dedicated agro-climate risk indicators. The initial set of these indicators has been developed in a co-design approach with agronomists and durum wheat farmers participating as end-users in the H2020-MedGOLD project. Four groups of indicators characterize drought events, excessive wetness, cold stress and heat stress during sensitive growth stages. The proposed approach has been fully implemented as an R-package named Clisagri. The package is complemented with a set of optimization functions, which target optimal variety selection in terms of crop cycle duration.

Using reanalysis in crop monitoring and forecasting systems.

Weather observations are essential for crop monitoring and forecasting but they are not always available and in some cases they have limited spatial representativeness. Thus, reanalyses represent an alternative source of information to be explored. In this study, we assess the feasibility of reanalysis-based crop monitoring and forecasting by using the system developed and maintained by the European Commission- Joint Research Centre, its gridded daily meteorological observations, the biased-corrected reanalysis AgMERRA and the ERA-Interim reanalysis. We focus on Europe and on two crops, wheat and maize, in the period 1980-2010 under potential and water-limited conditions. In terms of inter-annual yield correlation at the country scale, the reanalysis-driven systems show a very good performance for both wheat and maize (with correlation values higher than 0.6 in almost all EU28 countries) when compared to the observations-driven system. However, significant yield biases affect both crops. All simulations show similar correlations with respect to the FAO reported yield time series. These findings support the integration of reanalyses in current crop monitoring and forecasting systems and point to the emerging opportunities linked to the coming availability of higher-resolution reanalysis updated at near real time.

Scaling like behaviour of resistivity observed in LaNiO3 thin films grown on SrTiO3 substrate by pulsed laser deposition.

We discuss the origin of the temperature dependence of resistivity ρ observed in highly oriented LaNiO3 thin films grown on SrTiO3 substrate by a pulsed laser deposition technique. All the experimental data are found to collapse into a single universal curve ρ(T, d) ∝ [T/T(sf)(d)]3/2 for the entire temperature interval (20K

TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells.

Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation of 5-methylcytosine (5mC) by the Ten-Eleven Translocation (TET) enzymes, has been detected. 5hmC is now considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the DNA methylation/demethylation machinery in MS. We assessed the expression of enzymes involved in DNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed also, DNA methylation analysis of specific promoters and analysis of global levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters. Furthermore, 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.

Adaptation as a genome-wide autoregulatory principle in the stress response of yeast.

The gene expression response of yeast to various types of stresses/perturbations shows a common functional and dynamical pattern for the vast majority of genes, characterised by a quick transient peak (affecting primarily short genes) followed by a return to the pre-stimulus level. Kinetically, this process of adaptation following the transient excursion can be modelled using a genome-wide autoregulatory mechanism by means of which yeast aims at maintaining a preferential concentration in its mRNA levels. The resulting feedback system explains well the different time constants observable in the transient response, while being in agreement with all the known experimental dynamical features. For example, it suggests that a very rapid transient can be induced also by a slowly varying concentration of the gene products.

Validation of suitable internal control genes for expression studies in aging.

Quantitative data from experiments of gene expression are often normalized through levels of housekeeping genes transcription by assuming that expression of these genes is highly uniform. This practice is being questioned as it becomes increasingly clear that the level of housekeeping genes expression may vary considerably in certain biological samples. To date, the validation of reference genes in aging has received little attention and suitable reference genes have not yet been defined. Our aim was to evaluate the expression stability of frequently used reference genes in human peripheral blood mononuclear cells with respect to aging. Using quantitative RT-PCR, we carried out an extensive evaluation of five housekeeping genes, i.e. 18s rRNA, ACTB, GAPDH, HPRT1 and GUSB, for stability of expression in samples from donors in the age range 35-74 years. The consistency in the expression stability was quantified on the basis of the coefficient of variation and two algorithms termed geNorm and NormFinder. Our results indicated GUSB be the most suitable transcript and 18s the least for accurate normalization in PBMCs. We also demonstrated that aging is a confounding factor with respect to stability of 18s, HPRT1 and ACTB expression, which were particularly prone to variability in aged donors.

Impact of an HPV diagnosis on the quality of life in young women.

OBJECTIVE: To evaluate the impact of the communication of an HPV diagnosis on the cognitive-behavioural aspect, emotional experiences, psychic-physical well-being, and psychosexual sphere in young women between the ages of 20 and 45. METHOD: During the period between February 2006 and March 2007, at the U.O. Department of Obstetrics and Gynecology of the ULSS 13 of Mirano (VE), we distributed three self-evaluating questionnaires (the CBA-20, the SAT-P, and the BISF-W) to 36 women who had been diagnosed with an HPV infection and 36 women who had never been diagnosed with HPV. RESULTS: 36% of the experimental group reacted to the diagnosis with fear and 29% reacted with anxiety, while in only 3% of the cases did the women react with anger. Significant differences emerged in two samples regarding state anxiety and obsessive and compulsive aspects, while there were no significant differences between the two groups regarding the subjective satisfaction with life quality and sexual function. A significant positive correlation was found between the sum of anxiety and fear expressed at the time of the diagnosis and the trait anxiety reported in the Cognitive Behavioural Assessment 2.0. CONCLUSIONS: The results indicate that the prevalent emotions felt at the time of the diagnosis are fear and anxiety. The persons who were diagnosed with an HPV infection resulted as having higher levels of trait anxiety, obsessions, compulsions, and above all, behaviours and worries related to hygiene and improbable infections.

[Experiencing the educational process in nursing with high risk pregnant women and their companions]. / Vivenciando o processo educativo em enfermagem com gestantes de alto risco e seus acompanhantes.

The present study is a picture of the educational process lived by hospitalized high-risk pregnant women and also by their companions, conducted at the University Hospital of the Federal University of Santa Catarina. It has been developed as a joint process with the clients, through dynamic interaction, as a set of actions in an effort to socialize knowledge and experiences. The goal is to offer greater autonomy to the clients, allowing the high risk pregnancy to be a peaceful, safe and joyful experience, beyond the fact of contributing with the construction of new knowledge about the being-and-living process of these women.

Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant.

The transplantation of satellite cells may constitute a strategy for rebuilding muscle fibres in inherited myopathies. However, its development requires a great understanding of the role of environmental signals in the regenerative process. It is therefore essential to identify the key events triggering and controlling this process in vivo. We investigated whether macrophages play a key role in the course of the regenerative process using skeletal muscle transplants from transgenic pHuDes-nls-LacZ mice. Before grafting, transplants were conditioned with macrophage inflammatory protein 1-beta (MIP 1-beta; stimulating the macrophages infiltration or vascular endothelial growth factor (VEGF) stimulating angiogenesis). Treatment of transplants with MIP 1-beta and VEGF both accelerated and augmented monocyte-macrophage infiltration and satellite cell differentiation and/or proliferation, as compared to controls. In addition, VEGF treatment enhanced the number of newly formed myotubes. When a complete depletion of host monocyte-macrophages was experimentally induced, no regeneration occurred in transplants. Our data suggest that the presence of blood borne macrophages is required for triggering the earliest events of skeletal muscle regeneration. The understanding of macrophage behaviour after muscle injury should allow us to develop future strategies of satellite cell transplantation as a treatment for muscular dystrophies.

Effect of glucose and heparin on mesangial alpha 1(IV)COLL and MMP-2/TIMP-2 mRNA expression.

Mesangial cells are responsible for the synthesis of mesangial matrix as well as its degradation, which is mediated by a number of proteolytic activities, including metalloproteinases (MMPs). Imbalanced matrix protein metabolism may be responsible for mesangial expansion and glomerulosclerosis in diabetic nephropathy. Heparin prevents this complication. In human and murine mesangial cell cultures, RT-PCR was able to detect mRNA expression for a number of molecules involved in the mesangial extracellular matrix turnover: type IV collagen [alpha 1(IV)COLL], MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10, and the tissue inhibitors TIMP-1 and TIMP-2. The expression of mRNA for alpha 1(IV)COLL and MMP-2/TIMP-2 balance was studied in human cells in the presence of high glucose and heparin. mRNAs for all the studied molecules were expressed at different levels. Interestingly, a shift in the balance of alpha 1(IV)COLL, MMP-2 and TIMP-2 was observed in high glucose, which was partially reversed by heparin supplementation. The new equilibrium was mostly due to the down-regulation of type IV collagen expression, rather than further reduction of potential proteolysis. Our data, while extending the list of potential mediators of mesangial matrix catabolism, highlight a molecular mechanism by which the pathogenesis of diabetic nephropathy may be sustained, and at the same time suggest that heparin may have the potential to correct this abnormality.

[Lovastatin in the treatment of hypercholesterolemia in non-insulin-dependent diabetes mellitus patients]. / A lovastatina no tratamento da hipercolesterolemia em portadores de diabete não dependente de insulina.

PURPOSE: To evaluate the effects of lovastatin as an hypocholesterolemic agent in non-insulin dependent diabetic (NIDDM) patients with high cholesterol plasma levels. METHODS: Twenty NIDDM patients were included in this study. Hypercholesterolemia was defined as LDL-cholesterol plasma levels above 160mg/dl in female patients and above 130mg/dl in male patients or in women presenting any other risk factor for cardiovascular disease. From the 20 patients included, 18 had also high levels of arterial blood pressure. They were evaluated for admission in the study after they have substituted the antihypertensive medication for at least 6 weeks, from beta-blockers or diuretics to angiotensin converting enzyme inhibitors or calcium channel blockers. Lovastatin was administered in a initial daily dose of 20mg to all patients for 6 weeks. After this period this dose was increased to 40mg in 11 patients with LDL-cholesterol levels above 130mg/dl. All patients were treated for a total period of 24 weeks. RESULTS: Lovastatin therapy for 24 weeks reduced LDL-cholesterol and total cholesterol plasma levels in 30% and 21%, respectively, while no changes in HDL-cholesterol or triglycerides plasma levels were observed. The medication was well tolerated and no changes in bilirrubins or transaminases plasma levels were detected. In 9 patients the serum levels of alkaline phosphatase showed an elevation and the mean level of all group increased from 109 +/- 59 to 188 +/- 60m mu/ml (p < 0.05). This was an isolated abnormality without any other clinical manifestation. CONCLUSION: Lovastatin in NIDDM showed to be an efficient agent to reduce high levels of LDL-cholesterol and total cholesterol. However, the importance of the abnormality observed in serum alkaline phosphatase levels deserves further investigation. In this condition we recommend discontinuation of lovastatin therapy.

Thermal behaviour and binary phase diagram of (S)-(+)-4,4'-(1-methyl-1,2-ethandiyl)-bis-(2,6-piperazinedione) (dexrazoxane), a cardioprotective agent, and of its (R)-(-)-enantiomer.

The binary phase diagram of (S)-(+)-4,4'-(1-methyl-1,2-ethandiyl)-bis-(2,6-piperazinedione), 1 (dexrazoxane), a cardioprotective agent, and of its (R)-(-)-enantiomer, 2, has been investigated by differential scanning calorimetry (DSC); the equimolecular mixture of 1 and 2 corresponds to a racemic compound (racemate) whose melting point is higher than that of the enantiomers. Thermal behaviour (DSC) is examined and discussed in comparison with the data obtained by other physical methods (IR spectroscopy and X-ray powder diffraction).

[Dynamic evaluation of prolactin secretion in acromegaly (author's transl)]. / Avaliação dinâmica de secreção de prolactina na acromegalia.

The basal PRL levels and after estimulation with synthetic TRH were evaluated in 12 patients with active acromegaly, and in 12 normal individuals. None of the patients had galactorrhea and 5 of them had tumoral supra-sellar extension. Basal hyperprolactinemia was detected in 66% of the patients. After TRH stimulation, only 4 patients exhibited a percentual increment greater than 100% over the PRL basal value. PRL response to TRH was negative in 8 patients. The high PRL levels can be explained by the parallel production of GH and PRL by the tumoral cells, nevertheless a disturbance of the normal hypothalamic control cannot be excluded.