Introduction
Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
Objective
The aim of this ...study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.
Methods
In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.
Results
Sixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).
Conclusion
Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.
Alternatively activated macrophages (AAM) have regenerative and anti-inflammatory characteristics. Here, we sought to evaluate whether AAM cell therapy reduces renal inflammation and fibrosis in the ...unilateral ureteral obstruction (UUO) mice model.
We stabilized macrophages by adenoviral vector NGAL (Neutrophil gelatinase-associated lipocalin-2) and infused them into UUO mice. To ascertain whether macrophages were capable of reaching the obstructed kidney, macrophages were stained and detected by in vivo cell tracking.
We demonstrated that some infused macrophages reached the obstructed kidney and that infusion of macrophages overexpressing NGAL was associated with reduced kidney interstitial fibrosis and inflammation. This therapeutic effect was mainly associated with the phenotype and function preservation of the transferred macrophages isolated from the obstructed kidney Conclusions: Macrophage plasticity is a major hurdle for achieving macrophage therapy success in chronic nephropathies and could be overcome by transferring lipocalin-2.
In this paper we analyse the intensity and extent of agglomeration and co‐agglomeration of creative industries (CIs) in the metropolitan area of Barcelona (MAB). To do so, we use firm‐level ...geo‐located data to calculate distance‐based M and m functions of agglomeration and co‐agglomeration. Our results show that CIs are relatively more agglomerated than non‐CIs at short distances, and that each individual CI sector displays high levels of agglomeration (especially symbolic‐based sectors). Also, the co‐agglomeration of CIs and Non‐CIs is only observed for micro‐firms and that there is significant co‐agglomeration among symbolic‐based CI sectors. Finally, we confirm the role of the city‐centre of Barcelona as a magnet for CIs.
Resumen
En este artículo se analiza la intensidad y el alcance de la aglomeración y coaglomeración de las industrias creativas (IC) en el área metropolitana de Barcelona (AMB). Para ello se utilizaron datos geolocalizados a nivel de empresa con los que calcular las funciones M y m de aglomeración y coaglomeración, basadas en la distancia. Nuestros resultados muestran que las IC están relativamente más aglomeradas que las industrias no creativas (INC), y que cada sector individual de las IC presenta niveles elevados de aglomeración (especialmente los sectores de base simbólica). Además, la coaglomeración de las IC y las INC sólo se observa en el caso de las microempresas y existe una coaglomeración significativa entre los sectores de las IC de base simbólica. Por último, se confirma el papel del centro de la ciudad de Barcelona como un foco de atracción para las IC.
抄録:
本稿では、バルセロナ都市圏における、創造産業の集積と共集積の密度と程度を分析する。分析は、企業レベルの地理情報を基にしたデータを利用して、距離を基にした集積と共集積のMとmの関数を計算して実施する。結果から、創造産業は相対的に、互いの距離が短い非創造産業よりも集積度が高く、創造産業の各セクターは、(特に象徴的価値がベースのセクターでは)集積度が高レベルであることが示される。また、共集積は、創造産業と非創造産業においては零細企業にのみ認められ、創造産業の象徴的価値がベースのセクターでは顕著な共集積が存在する。結論として、バルセロナ市の中心部に創造産業の企業が引き寄せられていることが確認される。
Fruit production (NPPf), the amount of photosynthates allocated to reproduction (%GPPf) and their controls for spatial and species-specific variability (e.g. nutrient availability, climate) have been ...poorly studied in forest ecosystems. We characterized fruit production and its temporal behaviour for several tree species and resolved the effects of gross primary production (GPP), climate and foliar nutrient concentrations.
We used data for litterfall and foliar nutrient concentration from 126 European forests and related them to climatic data. GPP was estimated for each forest using a regression model.
Mean NPPf ranged from c. 10 to 40 g Cm−2 yr−1 and accounted for 0.5–3% of GPP. Forests with higher GPPs produced larger fruit crops. Foliar zinc (Zn) and phosphorus (P) concentrations were associated positively with NPPf, whereas foliar Zn and potassium (K) were negatively related to its temporal variability. Maximum NPPf and interannual variability of NPPf were higher in Fagaceae than in Pinaceae species.
NPPf and %GPPf were similar amongst the studied species despite the different reproductive temporal behaviour of Fagaceae and Pinaceae species. We report that foliar concentrations of P and Zn are associated with %GPPf, NPPf and its temporal behaviour.
Masting is the highly variable production of synchronized seed crops, and is a common reproductive strategy in plants. Weather has long been recognized as centrally involved in driving seed ...production in masting plants. However, the theory behind mechanisms connecting weather and seeding variation has only recently been developed, and still lacks empirical evaluation. We used 12-year long seed production data for 255 holm oaks (Quercus ilex), as well as airborne pollen and meteorological data, and tested whether masting is driven by environmental constraints: phenological synchrony and associated pollination efficiency, and drought-related acorn abscission. We found that warm springs resulted in short pollen seasons, and length of the pollen seasons was negatively related to acorn production, supporting the phenological synchrony hypothesis. Furthermore, the relationship between phenological synchrony and acorn production was modulated by spring drought, and effects of environmental vetoes on seed production were dependent on last year's environmental constraint, implying passive resource storage. Both vetoes affected among-tree synchrony in seed production. Finally, precipitation preceding acorn maturation was positively related to seed production, mitigating apparent resource depletion following high crop production in the previous year. These results provide new insights into mechanisms beyond widely reported weather and seed production correlations.
There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a ...well-defined echocardiographic methodology in a low-risk population.
This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation.
Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively).
We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling.
Calprotectin is produced by neutrophils and macrophages, and released during the acute phase of the ANCA vasculitis. The aim of our study was to determine if serum and urine calprotectin are disease ...activity and prognosis biomarkers in ANCA vasculitis patients during remission.
Forty-two ANCA vasculitis patients were included. Twenty-seven patients were in remission phase under immunosuppressive therapy, and 15 patients were in the acute phase. Four healthy controls were included. We determined calprotectin in serum and urine samples at the time of the inclusion. We recorded the incidence of relapse and the evolution of GFR, proteinuria, hematuria, and C reactive protein and ANCA titer during 24 months of follow-up.
In remission phase, serum calprotectin was higher than in healthy controls but lower compared to acute patients (p = 0.05). Serum calprotectin at inclusion was higher in patients who increased proteinuria during follow-up (p = 0.04), with hematuria (p = 0.08), and with non-decreasing ANCA titer (p = 0.0019). Serum calprotectin at inclusion in stable patients who subsequently decreased GFR during follow-up was higher compared with those with a stable or improving GFR (p = 0.03). Urine calprotectin was lower in patients with sclerotic histology in remission (p = 0.03) and acute phase (p = 0.12) compared to the rest of histologies.
Worsening of renal function, hematuria, rising proteinuria and non-decreasing ANCA correlated with higher levels of serum calprotectin at recruitment. Low urine calprotectin was found in patients with sclerotic histology. Calprotectin during remission in ANCA vasculitis may be useful to identify subclinical inflammation and worse renal prognosis patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human placenta exhibits a specific microRNA (miRNA) expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders such as preeclampsia and intrauterine growth restriction and are ...potential biomarkers for these pathologies.
To study the placental miRNA profile in pregnant women with pregestational overweight/obesity (preOB) or gestational obesity (gestOB) and explore the associations between placental miRNAs dysregulated in maternal obesity and prenatal and postnatal growth.
TaqMan Low Density Arrays and real-time polymerase chain reaction were used to profile the placental miRNAs in 70 pregnant women (20 preOB, 25 gestOB, and 25 control). Placentas and newborns were weighed at delivery, and infants were weighed at 1, 4, and 12 months of age.
Eight miRNAs were decreased in placentas from preOB or gestOB (miR-100, miR-1269, miR-1285, miR-181, miR-185, miR-214, miR-296, and miR-487) (all P < 0.05). Among them, miR-100, miR-1285, miR-296, and miR-487 were associated with maternal metabolic parameters (all P < 0.05) and were predictors of lower birth weight (all P < 0.05; R2 > 30%) and increased postnatal weight gain (all P < 0.05; R2 > 20%). In silico analysis showed that these miRNAs were related to cell proliferation and insulin signaling pathways. miR-296 was also present in plasma samples and associated with placental expression and prenatal and postnatal growth parameters (all P < 0.05).
We identified a specific placental miRNA profile in maternal obesity. Placental miRNAs dysregulated in maternal obesity may be involved in mediation of growth-promoting effects of maternal obesity on offspring and could be used as early markers of prenatal and postnatal growth.
Detecting and managing frailty at early stages can prevent disability and other adverse outcomes. The study aim was to evaluate whether a multifactorial intervention program could modify physical and ...cognitive frailty parameters in elderly individuals.
We conducted a multicenter, randomized, single-blind, parallel-group trial in community-living prefrail/frail elderly individuals in Barcelona. A total of 352 patients, aged ≥65 years old with positive frailty screening, was randomized into two groups to receive a 12-week multidisciplinary intervention or usual care, with concealed allocation. The intervention consisted of: exercise training, intake of hyperproteic nutritional shakes, memory training, and medication review. Main outcome assessments with multivariate analysis were conducted at 3 and 18 months.
A total of 347 participants (98.6%) completed the study, mean age 77.3 years, 89 prefrail subjects (25.3%), and 75.3% female (n = 265). Eighteen-month assessments were performed in 76% of the sample. After 3 and 18 months, adjusted means difference between-groups showed significant improvements for the intervention group in all comparisons: Short Physical Performance Battery score improved 1.58 and 1.36 points (p < .001), handgrip strength 2.84 and 2.49 kg (p < .001), functional reach 4.3 and 4.52 cm (p < .001), and number of prescriptions decreased 1.39 and 1.09 (p < .001), respectively. Neurocognitive battery also showed significant improvements across all dimensions at 3 and 18 months.
A physical, nutritional, neurocognitive, and pharmacological multifaceted intervention was effective in reversing frailty measures both at short-term and 18 months. Lasting benefits of a multi-intervention program among frail elderly individuals encourage its prioritization.
IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) ...treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg 95% CI, 0.6 to 5.6; P = .02) and 24-hour DBP (3.2 mm Hg 95% CI, 1.0 to 5.4; P = .005), but not in 24-hour SBP (3.1 mm Hg 95% CI, −0.6 to 6.7; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio OR, 2.4 95% CI, 1.2 to 5.1; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265
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