L'abordatge de l'assetjament escolar des de la mediació en la Justícia Juvenil de Catalunya

<div><p>The number of paralogs of proteins involved in translation initiation is larger in trypanosomes than in yeasts or many metazoan and includes two poly(A) binding proteins, PABP1 and PABP2, and four eIF4E variants. In many cases, the paralogs are individually essential and are thus unlikely to have redundant functions although, as yet, distinct functions of different isoforms have not been determined. Here, trypanosome PABP1 and PABP2 have been further characterised. PABP1 and PABP2 diverged subsequent to the differentiation of the Kinetoplastae lineage, supporting the existence of specific aspects of translation initiation regulation. PABP1 and PABP2 exhibit major differences in intracellular localization and distribution on polysome fractionation under various conditions that interfere with mRNA metabolism. Most striking are differences in localization to the four known types of inducible RNP granules. Moreover, only PABP2 but not PABP1 can accumulate in the nucleus. Taken together, these observations indicate that PABP1 and PABP2 likely associate with distinct populations of mRNAs. The differences in localization to inducible RNP granules also apply to paralogs of components of the eIF4F complex: eIF4E1 showed similar localization pattern to PABP2, whereas the localisation of eIF4E4 and eIF4G3 resembled that of PABP1. The grouping of translation initiation as either colocalizing with PABP1 or with PABP2 can be used to complement interaction studies to further define the translation initiation complexes in kinetoplastids.</p> </div

Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity

Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group

Epitope Mapping and Topographic Analysis of VAR2CSA DBL3X Involved in P. falciparum Placental Sequestration

Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in malaria endemic areas. The syndrome is precipitated by accumulation of infected erythrocytes in placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts and a parasite-encoded protein on the surface of infected erythrocytes, believed to be VAR2CSA. VAR2CSA is a polymorphic protein of approximately 3,000 amino acids forming six Duffy-binding-like (DBL) domains. For vaccine development it is important to define the antigenic targets for protective antibodies and to characterize the consequences of sequence variation. In this study, we used a combination of in silico tools, peptide arrays, and structural modeling to show that sequence variation mainly occurs in regions under strong diversifying selection, predicted to form flexible loops. These regions are the main targets of naturally acquired immunoglobulin gamma and accessible for antibodies reacting with native VAR2CSA on infected erythrocytes. Interestingly, surface reactive anti-VAR2CSA antibodies also target a conserved DBL3X region predicted to form an α-helix. Finally, we could identify DBL3X sequence motifs that were more likely to occur in parasites isolated from primi- and multigravidae, respectively. These findings strengthen the vaccine candidacy of VAR2CSA and will be important for choosing epitopes and variants of DBL3X to be included in a vaccine protecting women against pregnancy-associated malaria

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Localisation of receptors to estradiol, progesterone and androgen in the bovine cornea

Purpose: To investigate the density and spatial distribution of estradiol, progesterone and androgen receptors in corneal cryosections. Methods: Bovine corneas including the limbus were cryoprotected and snap frozen using isopentane cooled in liquid nitrogen. Cryosections of 10µm thickness were prepared and subjected to antibodies raised against receptors for estradiol, progesterone and androgen at dilutions of 1:10, 1:50 and 1:100 respectively. Staining was visualised using a Mouse ExtraAvidin® Peroxidase Staining Kit and nuclei were counterstained with bisbenzimide. Results: Assessment of tissue sections demonstrated immunostaining for estradiol, progesterone, and androgen receptors in the epithelium and in the keratocytes. Staining for all three receptors was nuclear and was detected in the limbal and peripheral regions of the cornea in both basal and suprabasal cell layers. With respect to the central corneal regions immunostaining was more diffuse within the cell layers. Immunostaining for all receptors was nuclear in the keratocytes throughout the corneal stroma. Conclusions: Estradiol, progesterone and androgen receptors are present in the epithelium and the stroma of the cornea and may be influenced by their ligands that we have previously identified in the tear film. It is likely that sex hormones may regulate cell-cell interactions during corneal wound healing

Designing and managing sustainable settlements with appropriate housing and infrastructure

Designing and managing a successful sustainable settlement is a multidisciplinary task involving cooperation and consultation between many parties. Sustainable development highlights the fact that all life is interrelated, insofar as a settlement must meet the needs of the present without compromising the ability of future generations to meet their needs.\ud \ud The built environment is not equated with the socio-economic and demographic characteristics of individual residents, but includes housing form, roads and footpaths, parks and other public amenities. The effects of the built environment on social interaction, including crime, are most salient for health and thus sustainability. Independently rated features of the built environment are associated with depression and poor health, independent of individual socio-economic status.\ud \ud Therefore appropriate housing and infrastructure are fundamental to creating a sustainable settlement in which the population is healthy and happy. Housing of appropriate size to meet the requirements of the occupants is crucial. Having adequate infrastructure to support a community in terms of essential services like sewerage, power, water and adequate waste management, is also important. In the following chapter emphasis has been placed on the rural and remote Indigenous communities of Australia where the issues of overcrowding, appropriate housing and adequate infrastructure are paramount

The predicted NLS of PABP2 is not an NLS. A)

<p>Fluorescent microscopy images of cells expressing PABP1-eYFP/PABP2-mChFP either untreated or treated with sinefungin (2 µg/ml), heat shock (41°C) or both sinefungin and heat shock for two hours. <b>B)</b> Alignment of TbPABP1, TbPABP2 and ScPAB1p (region between RRM 3 and 4). The predicted NLS of TbPABP2 is highlighted, as well as the NLS of the yeast protein PAB1p <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054004#pone.0054004-Brune1" target="_blank">[74]</a>. <b>C and D)</b> The predicted NLS of <i>T. brucei</i> PABP2 (RLRRER) was exchanged with the equivalent region from PABP1 (ALRQKY) (<b>C</b>) and vice versa (<b>D</b>). Both mutant proteins had cytoplasmic localization identical to the wild type proteins (not shown). Fluorescent microscopy images of untreated cells as well as cells treated with sinefungin, heat shock or both are shown.</p

Summary of localization to granules and co-localization shown in this study.

1<p>*low expression levels.</p>2<p>*localization to PBS granules at over-expression.</p