CONTEXT In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became ...insulin free with normal levels of glycated hemoglobin A1c (HbA1c) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. OBJECTIVE To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective phase 1/2 study of 23 patients with type 1 DM (aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti–glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. MAIN OUTCOME MEASURES C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA1c. RESULTS During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin–independent group, HbA1c levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P < .001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P = .001). In the transient insulin–independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P = .001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. CONCLUSION After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00315133
Aim
The aim of this study was to evaluate the potential anti‐Candida effects of Lactobacillus rhamnosus ATCC 9595 on Candida albicans ATCC 18804 using in vitro and in vivo models.
Methods and Results
...The in vitro analysis evaluated the effects of L. rhamnosus on C. albicans's biofilm formation by CFU count and metabolic activity, filamentation capacity, and adhesion (ALS3 and HWP1) and transcriptional regulatory gene (BCR1 and CPH1) expression. The in vitro results showed that both the L. rhamnosus cells and supernatant reduced C. albicans biofilm formation, filamentation and gene expression. In the in vivo study, the treatment with L. rhamnosus supernatant increased 80% the survival of Galleria mellonella larvae infected with C. albicans. Furthermore, the supernatant of L. rhamnosus recruited haemocytes into the haemolymph (2·1‐fold increase).
Conclusions
Lactobacillus rhamnosus reduced the biofilm formation and filamentation of C. albicans in vitro by negatively regulating all studied C. albicans genes. Lactobacillus rhamnosus protected G. mellonella against experimental candidiasis in vivo.
Significance and Impact of the Study
This study is the first study to report the anti‐Candida properties of L. rhamnosus ATCC 9595. The supernatant of this strain has immunomodulatory effects on the G. mellonella model and protects the larvae against pathogens.
Nutrient accumulation in man-made reservoirs has been documented worldwide. Therefore, quantifying phosphorus loading and understanding its temporal dynamics in reservoirs is mandatory for ...sustainable water management. In this study, the Vollenweider's complete-mix phosphorus budget model was adapted to account for high water level variations, which are a common feature in tropical reservoirs, and for internal phosphorus loads. First- and zero-order kinetics were adopted to simulate phosphorus settling and release from the sediment layer, respectively, considering variable area of phosphorus release according to the height of the anoxic layer. The modeling approach was applied for a 52-months period to a 31-years-old reservoir located in the semiarid region of Brazil with 7.7 hm3 storage capacity. The simulations were supported by hydrological, meteorological and water quality data, as well as analyses of phosphorus partitioning of the reservoir bed sediment. The external phosphorus load was estimated from a relationship adjusted between inflow and phosphorus concentration, revealing an u-shaped pattern. Sedimentary phosphorus linked to iron and aluminum (PFeAl) increased over time and along the reservoir. Such measurements were used to estimate the internal phosphorus load, i.e., the yield from the bed sediments to the water column. The adaptations proposed to the model's structure improved its capacity to simulate phosphorus concentration in the water column, from “not satisfactory” to “good”. We estimate that the internal phosphorus load currently accounts for 44% of the total load. It prevailed during the wet period, when reservoir stratification and hypolimnetic hypoxia were more notable, resulting in higher phosphorus concentration in the water column due to the combined effects of internal and external loadings. However, if the reservoir were 70 years older, the internal load would reach 83% of the total and the reservoir would become a source instead of a sink of phosphorus.
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•P linked to iron and aluminum (PFeAl) increased over time and along the reservoir bed.•Internal P loads were estimated from PFeAl and variable heights of the anoxic layer.•Adaptation of Vollenweider's model improved P predictions in the water.•Internal load prevailed in the wet period and was slightly lower than external load.•The internal load would increase by 6-fold if the reservoir were 70 years older.
Context. With only two functional reaction wheels, Kepler cannot maintain stable pointing at its original target field and has entered a new mode of observation called K2. Aims. We describe a new ...pipeline to reduce K2 pixel files into light curves that are later searched for transit like features. Methods. Our method is based on many years of experience in planet hunting for the CoRoT mission. Owing to the unstable pointing, K2 light curves present systematics that are correlated with the target position in the charge coupled device (CCD). Therefore, our pipeline also includes a decorrelation of this systematic noise. Our pipeline is optimised for bright stars for which spectroscopic follow-up is possible. We achieve a maximum precision on 6 hours of 6 ppm. The decorrelated light curves are searched for transits with an adapted version of the CoRoT alarm pipeline. Results. We present 172 planetary candidates and 327 eclipsing binary candidates from campaigns 1, 2, 3, 4, 5, and 6 of K2. Both the planetary candidates and eclipsing binary candidates lists are made public to promote follow-up studies. The light curves will also be available to the community.
Previous research has shown that fires burn certain land cover types disproportionally to their abundance. We used quantile regression to study land cover proneness to fire as a function of fire ...size, under the hypothesis that they are inversely related, for all land cover types. Using five years of fire perimeters, we estimated conditional quantile functions for lower (avoidance) and upper (preference) quantiles of fire selectivity for five land cover types - annual crops, evergreen oak woodlands, eucalypt forests, pine forests and shrublands. The slope of significant regression quantiles describes the rate of change in fire selectivity (avoidance or preference) as a function of fire size. We used Monte-Carlo methods to randomly permutate fires in order to obtain a distribution of fire selectivity due to chance. This distribution was used to test the null hypotheses that 1) mean fire selectivity does not differ from that obtained by randomly relocating observed fire perimeters; 2) that land cover proneness to fire does not vary with fire size. Our results show that land cover proneness to fire is higher for shrublands and pine forests than for annual crops and evergreen oak woodlands. As fire size increases, selectivity decreases for all land cover types tested. Moreover, the rate of change in selectivity with fire size is higher for preference than for avoidance. Comparison between observed and randomized data led us to reject both null hypotheses tested (Formula: see text = 0.05) and to conclude it is very unlikely the observed values of fire selectivity and change in selectivity with fire size are due to chance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rates of preterm birth are increasing worldwide and this increase is mostly due to infants born between 34 and 36 weeks of gestational age, the so-called "late preterm" births. The aim of this study ...was to assess the effect of late preterm birth over growth outcomes, assessed when children were 12 and 24 months old.
In 2004, all births taking place in Pelotas (Southern Brazil) were recruited for a cohort study. Late preterm (34/0-36/6 weeks of gestational age) and term children (37/0-42/6 weeks) were compared in terms of weight-for-age, length-for-age and weight-for-length z-scores. Weight-for-age, length-for-age and weight-for-length z-scores below -2 were considered, respectively, underweight, stunting and wasting. Singleton newborns with adequate weight for gestational age at birth, successfully followed-up either at 12 or 24 months of age were analyzed and adjusted odds ratios with 95% confidence intervals calculated through logistic regression.
3285 births were included, 371 of whom were late preterm births (11.3%). At 12 months, prevalence of underweight, stunting and wasting were, respectively, 3.4, 8.7 and 1.1% among late preterm children, against 1.0, 3.4 and 0.3% among term children. At 24 months, correspondent values were 3.0, 7.2 and 0.8% against 0.8, 2.9 and 0.4%. Comparing with the term children, adjusted odds of being underweighted among late preterm children was 2.57 times higher (1.27; 5.23) at 12 months and 3.36 times higher (1.56; 7.23) at 24; of being stunted, 2.35 (1.49; 3.70) and 2.30 (1.40; 3.77); and of being wasted, 3.98 (1.07; 14.85) and 1.87 (0.50; 7.01). Weight gain from birth to 12 and 24 months was similar in late preterm and term children, whereas length gain was higher in the former group in both periods.
Late preterm children grow faster than children born at term, but they are at increased risk of underweight and stunting in the first two years of life. Failure to thrive in the first two years may put them at increased risk of future occurrences of serious morbidity in late childhood and of chronic disease development in adult life.
The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and ...lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review.
Context. Short-period planets are influenced by the extreme tidal forces of their parent stars. These forces deform the planets causing them to attain nonspherical shapes. The nonspherical shapes, ...modeled here as triaxial ellipsoids, can have an impact on the observed transit light-curves and the parameters derived for these planets. Aims. We investigate the detectability of tidal deformation in short-period planets from their transit light curves and the instrumental precision needed. We also aim to show how detecting planet deformation allows us to obtain an observational estimate of the second fluid Love number from the light curve, which provides valuable information about the internal structure of the planet. Methods. We adopted a model to calculate the shape of a planet due to the external potentials acting on it and used this model to modify the ellc transit tool. We used the modified ellc to generate the transit light curve for a deformed planet. Our model is parameterized by the Love number; therefore, for a given light curve we can derive the value of the Love number that best matches the observations. Results. We simulated the known cases of WASP-103b and WASP-121b which are expected to be highly deformed. Our analyses show that instrumental precision ≤50 ppm min−1 is required to reliably estimate the Love number and detect tidal deformation. This precision can be achieved for WASP-103b in ∼40 transits using the Hubble Space Telescope and in ∼300 transits using the forthcoming CHEOPS instrument. However, fewer transits will be required for short-period planets that may be found around bright stars in the TESS and PLATO survey missions. The unprecedented precisions expected from PLATO and JWST will permit the detection of shape deformation with a single transit observation. However, the effects of instrumental and astrophysical noise must be considered as they can increase the number of transits required to reach the 50 ppm min−1 detection limit. We also show that improper modeling of limb darkening can act to bury signals related to the shape of the planet, thereby leading us to infer sphericity for a deformed planet. Accurate determination of the limb darkening coefficients is therefore required to confirm planet deformation.
Context.
Proxima Centauri is the closest star to the Sun. This small, low-mass, mid M dwarf is known to host an Earth-mass exoplanet with an orbital period of 11.2 days within the habitable zone, as ...well as a long-period planet candidate with an orbital period of close to 5 yr.
Aims.
We report on the analysis of a large set of observations taken with the ESPRESSO spectrograph at the VLT aimed at a thorough evaluation of the presence of a third low-mass planetary companion, which started emerging during a previous campaign.
Methods.
Radial velocities (RVs) were calculated using both a cross-correlation function (CCF) and a template matching approach. The RV analysis includes a component to model Proxima’s activity using a Gaussian process (GP). We use the CCF’s full width at half maximum to help constrain the GP, and we study other simultaneous observables as activity indicators in order to assess the nature of any potential RV signals.
Results.
We detect a signal at 5.12 ± 0.04 days with a semi-amplitude of 39 ± 7 cm s
−1
. The analysis of subsets of the ESPRESSO data, the activity indicators, and chromatic RVs suggest that this signal is not caused by stellar variability but instead by a planetary companion with a minimum mass of 0.26 ± 0.05
M
⊕
(about twice the mass of Mars) orbiting at 0.029 au from the star. The orbital eccentricity is well constrained and compatible with a circular orbit.
This longitudinal study explored the relationship between trajectories of maternal depressive symptoms and offspring's risk behavior in adolescence contributing to an extremely scarce literature ...about the impacts of maternal depression trajectories on offspring risk behaviors.
We included 3437 11-year-old adolescents from the 2004 Pelotas Birth Cohort Study. Trajectories of maternal depressive symptoms were constructed using Edinburgh Postnatal Depression Scale (EDPS) from age 3 months to 11 years. We identified five trajectories of maternal depressive symptoms: "low" "moderate low", "increasing", "decreasing", and "chronic high". The following adolescent outcomes were identified via self-report questionnaire and analyzed as binary outcome -yes/no: involvement in fights and alcohol use at age 11. We used logistic regression models to examine the effects of trajectories of maternal depressive symptoms on offspring's risk behavior adjusting for potential confounding variable.
Alcohol use and/or abuse as well as involvement in fights during adolescence, were not significantly associated with any specific trajectory of maternal depressive symptoms neither in the crude nor in the adjusted analyses.
Alcohol use and involvement in fights at age 11 were not associated with any specific trajectory of maternal depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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