This work aims to study seeds of the endemic species Astragalus aquilanus from four different populations of central Italy. We investigated seed morpho-colorimetric features (shape and size) and ...chemical differences (through infrared spectroscopy) among populations and between dark and light seeds. Seed morpho-colorimetric quantitative variables, describing shape, size and colour traits, were measured using image analysis techniques. Fourier transform infrared (FT-IR) spectroscopy was used to attempt seed chemical characterisation. The measured data were analysed by step-wise linear discriminant analysis (LDA). Moreover, we analysed the correlation between the four most important traits and six climatic variables extracted from WorldClim 2.0. The LDA on seeds traits shows clear differentiation of the four populations, which can be attributed to different chemical composition, as confirmed by Wilk's lambda test (P < 0.001). A strong correlation between morphometric traits and temperature (annual mean temperature, mean temperature of the warmest and coolest quarter), colorimetric traits and precipitation (annual precipitation, precipitation of wettest and driest quarter) was observed. The characterisation of A. aquilanus seeds shows large intraspecific plasticity both in morpho-colorimetric and chemical composition. These results confirm the strong relationship between the type of seed produced and the climatic variables.
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•Formation of metallic hydrides by ultrasonic treatments of metallic slurries.•Observation of cavitation bubbles action/erosion on metallic surface.•Application for hydrogenation of ...several intermetallic alloys.
We report the sonochemical synthesis of hydrogenated metallic microparticles through room-temperature ultrasonic irradiation of aqueous metallic slurries. The role of saturating gases and of reduction-oxidation mechanism on promoting the hydride formation is investigated. The method is then applied to study the synthesis of different metallic hydrides (Mn, Ti) and the hydrogenation of La(Fe,Mn,Si)13, an intermetallic compound with magnetocaloric properties used in magnetic refrigeration applications. The samples were characterized by X-ray diffraction to identify the presence of hydrogenated phases, by differential scanning calorimetry to evaluate hydrogen release and temperature stability of the hydrides and by electron microscopy to identify morphological modifications induced by acoustic cavitation. The hydrogenation of metallic microparticles and intermetallic compounds is reported for the first time by means of this experimental technique which could represent a new tool for fast and cheap hydrogenation of materials for different technological applications, such as hydrogen storage and magnetic refrigeration.
Background Recent literature suggests that obese critically ill patients do not have worse outcomes than patients who are normal weight. However, outcomes in extreme obesity (BMI ≥ 40 kg/m2 ) are ...unclear. We sought to determine the association between extreme obesity and ICU outcomes. Methods We analyzed data from a multicenter international observational study of ICU nutrition practices that occurred in 355 ICUs in 33 countries from 2007 to 2009. Included patients were mechanically ventilated adults ≥ 18 years old who remained in the ICU for > 72 h. Using generalized estimating equations and Cox proportional hazard modeling with clustering by ICU and adjusting for potential confounders, we compared extremely obese to normal-weight patients in terms of duration of mechanical ventilation (DMV), ICU length of stay (LOS), hospital LOS, and 60-day mortality. Results Of the 8,813 patients included in this analysis, 3,490 were normal weight (BMI 18.5-24.9 kg/m2 ), 348 had BMI 40 to 49.9 kg/m2 , 118 had BMI 50 to 59.9 kg/m2 , and 58 had BMI ≥ 60 kg/m2 . Unadjusted analyses suggested that extremely obese critically ill patients have improved mortality (OR for death, 0.77; 95% CI, 0.62-0.94), but this association was not significant after adjustment for confounders. However, an adjusted analysis of survivors found that extremely obese patients have a longer DMV and ICU LOS, with the most obese patients (BMI ≥ 60 kg/m2 ) also having longer hospital LOS. Conclusions During critical illness, extreme obesity is not associated with a worse survival advantage compared with normal weight. However, among survivors, BMI ≥ 40 kg/m2 is associated with longer time on mechanical ventilation and in the ICU. These results may have prognostic implications for extremely obese critically ill patients.
In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, ...collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995.
Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy
vs no radiotherapy, 23 500; more
vs less surgery, 9300; more surgery
vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17 000 women; >10%, 25 000 women).
About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44·6% versus 49·5% (absolute reduction 5·0%, SE 0·8, 2p<0·00001).
These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54·7% versus 60·1% (reduction 5·4%, SE 1·3, 2p=0·0002; overall mortality reduction 4·4%, SE 1·2, 2p=0·0009). Radiotherapy produced similar
proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large
absolute reductions in local recurrence were seen only if the control risk was large.
To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1·18, SE 0·06, 2p=0·002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1·12, SE 0·04, 2p=0·001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1·27, SE 0·07, 2p=0·0001) and lung cancer (rate ratio 1·78, SE 0·22, 2p=0·0004).
In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.
Transcription factor EB (TFEB) is a master regulator of genes involved in the maintenance of autophagic and lysosomal homeostasis, processes which have been implicated in the pathogenesis of
GBA
...-related and sporadic Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). TFEB activation results in its translocation from the cytosol to the nucleus. Here, we investigated TFEB subcellular localization and its relation to intracellular alpha-synuclein (aSyn) accumulation in
post-mortem
human brain of individuals with either incidental Lewy body disease (iLBD),
GBA
-related PD/DLB (
GBA
-PD/DLB) or sporadic PD/DLB (sPD/DLB), compared to control subjects. We analyzed nigral dopaminergic neurons using high-resolution confocal and stimulated emission depletion (STED) microscopy and semi-quantitatively scored the TFEB subcellular localization patterns. We observed reduced nuclear TFEB immunoreactivity in PD/DLB patients compared to controls, both in sporadic and
GBA
-related cases, as well as in iLBD cases. Nuclear depletion of TFEB was more pronounced in neurons with Ser129-phosphorylated (pSer129) aSyn accumulation in all groups. Importantly, we observed previously-unidentified TFEB-immunopositive perinuclear clusters in human dopaminergic neurons, which localized at the Golgi apparatus. These TFEB clusters were more frequently observed and more severe in iLBD, sPD/DLB and
GBA
-PD/DLB compared to controls, particularly in pSer129 aSyn-positive neurons, but also in neurons lacking detectable aSyn accumulation. In aSyn-negative cells, cytoplasmic TFEB clusters were more frequently observed in
GBA
-PD/DLB and iLBD patients, and correlated with reduced
GBA
enzymatic activity as well as increased Braak LB stage. Altered TFEB distribution was accompanied by a reduction in overall mRNA expression levels of selected TFEB-regulated genes, indicating a possible early dysfunction of lysosomal regulation. Overall, we observed cytoplasmic TFEB retention and accumulation at the Golgi in cells without apparent pSer129 aSyn accumulation in iLBD and PD/DLB patients. This suggests potential TFEB impairment at the early stages of cellular disease and underscores TFEB as a promising therapeutic target for synucleinopathies.
To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on ...both large and small airways in asthma. Allergy 2010; 65: 897-902. Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 μg daily or fluticasone propionate/salmeterol (FP/S) 500/100 μg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV₁) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV₁ in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD₂₀FEV₁ Mch improved significantly from 90.42 (±30.08) μg to 432.41 (±122.71) μg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN₂ test parameters. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN₂ tests.
Abstract Age determination in amphibians is crucial to the investigation of life-history traits. In this context, we studied, for the first time, the life-history traits of Boana pulchella from a ...sample (63 adult males) of three populations (Las Acequias, Río Cuarto, Alejandro Roca) in central Argentina using the skeletochronological method. All adults of B. pulchella studied showed recognizable bone structures that allowed age determination. The average snout-vent length of sexually mature males was 43.39 mm. The maximum observed longevity was 5 years (5 Las Acequias, 4 Río Cuarto, 3 Alejandro Roca) and minimum age at sexual maturity was 2 years (same in the three populations), with mean of 2.96 years. Body size and age were positively correlated (except in Alejandro Roca populations). The growth patterns, estimated by the von Bertalanffy growth equation, do not show differences between populations, and the growth rate decrease after the attainment of sexual maturity. In conclusion, the determination of the individual age of the different populations of B. pulchella allowed us for the first time to establish the characteristics of the life history of the species, important for future comparisons whit others populations and future conservation biology studies.
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