The assembly of a collection of gene-expression signatures of the major types of B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma 1A (TCL1) expression in multiple ...lymphoma types and cases, and has enabled the investigation of the functional and clinical importance of TCL1 expression. Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic marginal zone lymphoma display a striking variability in the intensity of TCL1 staining. This was validated in two independent series. A Gene-Set Enrichment Analysis of the genes correlated with TCL1A expression found that variation in the level of expression of TCL1A was significantly associated with some of the most important gene signatures recognizing B-cell lymphoma pathogenesis and heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1 expression was correlated with shorter time to treatment in chronic lymphocytic leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma series, thus indicating the clinical and biological significance of TCL1 expression, and suggesting TCL1A as a potential therapeutic target.
The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on ...cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.
The structural and electronic properties of Ce{sub 1-x}Ni{sub x}O{sub 2-y} nanosystems prepared by a reverse microemulsion method were characterized with synchrotron-based X-ray diffraction, X-ray ...absorption spectroscopy, Raman spectroscopy, and density functional calculations. The Ce{sub 1-x}Ni{sub x}O{sub 2-y} systems adopt a lattice with a fluorite-type structure with an acute local order where Ni displays a strongly distorted (oxygen) nearest-neighbor coordination and the presence of Ni atoms as first cation distances, pointing to the existence of Ni-O-Ni entities embedded into the ceria lattice. A Ni {leftrightarrow} Ce exchange within the CeO{sub 2} leads to a charge redistribution and the appearance of O vacancies. The Ni-O bonds in Ce{sub 1-x}Ni{sub x}O{sub 2-y} are more difficult to reduce than the bonds in pure NiO. The specific structural configuration of Ni inside the mixed-metal oxide leads to a unique catalyst with a high activity for the water gas shift (CO + H{sub 2}O {yields} H{sub 2} + CO{sub 2}) reaction and a simultaneous reduction of the methanation activity of nickel. Characterization results indicate that small particles of metallic Ni at the interface position of a ceria network may be the key for high WGS activity and that the formate-carbonate route is operative for the production of hydrogen.
Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have ...been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear.
This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese.
A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire.
The mHealth intervention produced a greater loss of body weight (-1.97 kg, 95% CI -2.39 to -1.54) relative to standard counselling at 3 months (-1.13 kg, 95% CI -1.56 to -0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; -1.84 kg, 95% CI -2.48 to -1.20), percentage of body fat (PBF; -1.22%, 95% CI -1.82% to 0.62%), and BMI (-0.77 kg/m
, 95% CI -0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of -1.18 kg (95% CI -2.30 to -0.06) and BMI of -0.47 kg/m
(95% CI -0.80 to -0.13), whereas the obese group only experienced a change in BMI of -0.53 kg/m
(95% CI -0.86 to -0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of -1.03 kg (95% CI -1.74 to -0.33), PBF of -0.76% (95% CI -1.32% to -0.20%), and BMI of -0.5 kg/m
(95% CI -0.83 to -0.19).
The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m
and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect.
Clinicaltrials.gov NCT03175614; https://clinicaltrials.gov/ct2/show/NCT03175614.
RR2-10.1097/MD.0000000000009633.
Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable ...factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis.
Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations.
Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p = 0.005, more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p = 0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p = 0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline.
Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.
Our aim was to evaluate whether the number of circulating lymphocytes expressing costimulatory molecules can be associated with melanoma prognosis. We determined the concentration of peripheral blood ...lymphocytes, which expressed the CD80/CD86 or CD28/CTLA-4 molecules, in 38 patients with cutaneous melanoma and 27 controls. The number of each cell subset was compared between patients and controls, as well as between groups of patients stratified according to Breslow thickness of the primary tumor (≤ 2 mm vs > 2 mm) or to survival after 3 years. The concentration of circulating lymphocytes expressing the CD80/CD86 molecules was not significantly different between patients and controls. There was a lower number of CD3
+CD8
+CD28
+ cells, as well as a higher CD3
+CD8
+/CD3
+CD8
+CD28
+ cell ratio, in melanoma patients than in controls. Melanoma patients with thinner tumors and those surviving revealed an increase of CD19
+CD80
+ and CD19
+CD80
+CD86
+ cells, as well as a higher concentration of CD3
+CD4
+CD28
+ cells. CD80
+ B cells and a low CD8 suppressor/cytolytic cell ratio correlate with a good prognosis in melanoma. Our findings support our conclusion that CD80
+ B cells may be important antigen presenting cells that can contribute to an antimelanoma immune response and are candidates to be monitored in melanoma patients.
Background Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early ...intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)–based experimental studies, the β1 -blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. Objective The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. Design The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. Conclusions The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI.
Agroecosystems main function is food, fiber and fodder provision. However, other ecosystem services (ES) are provided by these systems, such as the reduction of soil loss or the enjoyment of the ...landscape. Many of these ES do not take part in the market, but their valuation is important to develop a sustainable management of the system. Valuing ES requires a clear classification of ES and some efforts on the study and clarification of the ES classification has been carried out. Nevertheless, the assessment of non-market benefits requires defining and classifying ES according to the type of ecosystem studied and prioritizing the ES impact on social well-being. Thus, this work aims to develop an adaptation of the existing ES classification for irrigated agroecosystem ES valuation, and verify it through an agricultural stakeholders’ consultation. Their contribution could permit to advance towards agricultural ES valuation. It would allow the implementation of management and policy actions which take into account the importance of agroecosystem ES provision and their impact on human well-being.
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