Continuous Positive Airway Pressure Effect on Albuminuria Progression in Patients with Obstructive Sleep Apnea and Diabetic Kidney Disease: A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic kidney disease (DKD). However, the effect of apnea-hypopnea suppression on DKD progression is unclear. Objectives: To assess the effect of continuous positive airway pressure (CPAP) on the urinary albumin-to-creatinine ratio (UACR) in patients with DKD and OSA. Methods: In a 52-week, multicentric, open-label, parallel, and randomized clinical trial, 185 patients with OSA and DKD were randomized to CPAP and usual care (n = 93) or usual care alone (n = 92). Measurements and Main Results: UACR, estimated glomerular filtration rate, serum concentrations of creatinine and glycated hemoglobin, insulin resistance, lipid concentrations, sleepiness, and quality of life. A 52-week change in UACR from baseline did not differ significantly between the CPAP group and the usual-care group. However, in per-protocol analyses that included 125 participants who met prespecified criteria for adherence, CPAP treatment was associated with a great reduction in UACR (mean difference, -10.56% [95% confidence interval, -19.06 to -2.06]; P = 0.015). CPAP effect on UACR was higher in nonsleepy patients with more severe OSA, worse renal function, and a more recent diagnosis of DKD. CPAP treatment also improved glycemic control and insulin resistance, as well as sleepiness and health-related quality of life. Conclusions: In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared with usual care alone. Clinical trial registered with www.clinicaltrials.gov (NCT02816762).

International Comparison Exercise for Biological Dosimetry after Exposures with Neutrons Performed at Two Irradiation Facilities as Part of the BALANCE Project.

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated, and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0-4 Gy at two different facilities in Germany (Physikalisch-Technische Bundesanstalt [PTB]) and the USA (the Columbia IND Neutron Facility [CINF]). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semiautomatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semiautomatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed nonlinear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study.

BACKGROUND: Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). METHODS: Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. RESULTS: Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. CONCLUSIONS: Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

Six hundred years of South American tree rings reveal an increase in severe hydroclimatic events since mid-20th century.

South American (SA) societies are highly vulnerable to droughts and pluvials, but lack of long-term climate observations severely limits our understanding of the global processes driving climatic variability in the region. The number and quality of SA climate-sensitive tree ring chronologies have significantly increased in recent decades, now providing a robust network of 286 records for characterizing hydroclimate variability since 1400 CE. We combine this network with a self-calibrated Palmer Drought Severity Index (scPDSI) dataset to derive the South American Drought Atlas (SADA) over the continent south of 12°S. The gridded annual reconstruction of austral summer scPDSI is the most spatially complete estimate of SA hydroclimate to date, and well matches past historical dry/wet events. Relating the SADA to the Australia-New Zealand Drought Atlas, sea surface temperatures and atmospheric pressure fields, we determine that the El Niño-Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) are strongly associated with spatially extended droughts and pluvials over the SADA domain during the past several centuries. SADA also exhibits more extended severe droughts and extreme pluvials since the mid-20th century. Extensive droughts are consistent with the observed 20th-century trend toward positive SAM anomalies concomitant with the weakening of midlatitude Westerlies, while low-level moisture transport intensified by global warming has favored extreme rainfall across the subtropics. The SADA thus provides a long-term context for observed hydroclimatic changes and for 21st-century Intergovernmental Panel on Climate Change (IPCC) projections that suggest SA will experience more frequent/severe droughts and rainfall events as a consequence of increasing greenhouse gas emissions.

The impact of early versus delayed cord clamping on hematological and cardiovascular changes in preterm newborns between 24 and 34 weeks' gestation: a randomized clinical trial.

PURPOSE: This study aimed to   investigate hematological and cardiac changes after early (ECC) versus delayed cord clamping (DCC) in preterm infants at 24-34 weeks of gestation. METHODS: Ninety-six healthy pregnant women were assigned randomly to the ECC (< 10 s postpartum, n = 49) or DCC (45-60 s postpartum, n = 47). Primary endpoint was evaluation of neonatal hemoglobin, hematocrit and bilirrubin levels within the first 7 days after birth. A postpartum blood test was performed in the mother and a neonatal echocardiography in the first week of life. RESULTS: We found differences in hematological parameters during the first week of life. On admission, the DCC group had higher hemoglobin levels than the ECC group (18.7 ± 3.0 vs. 16.8 ± 2.4, p < 0.0014) and higher hematocrit values (53.9 ± 8.0 vs. 48.8 ± 6.4, p < 0.0011). Around day 7 of life, hemoglobin levels were also higher in the DCC group compared with the ECC group (16.4 ± 3.8 vs 13.9 ± 2.5, p < 0.005), as was the hematocrit (49.3 ± 12.7 vs 41.2 ± 8.4, p < 0.0087). The need of transfusion was lower in the DCC compared to the ECC (8.5% vs 24.5%; OR: 0.29, 95% CI: 0.09-0.97, p < 0.036). The need for phototherapy was also higher in the DCC (80.9% vs 63.3%; OR: 0.23, 95% CI: 0.06-0.84, p < 0.026). No differences in cardiac parameters or maternal blood tests. CONCLUSION: DCC improved neonatal hematological parameters. No changes in cardiac function were found and maternal blood loss did not increase to require transfusion.

Accuracy of Xpert Ultra for the diagnosis of paediatric tuberculosis in a low TB burden country: a prospective multicentre study.

INTRODUCTION: Childhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting. METHODS: Prospective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel. RESULTS: 86 children were included (median age 4.9 years, IQR 2.0-10.0; 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%); 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194; 88.6%) and sputum specimens (n=25; 11.4%), were analysed. Using culture as reference standard and comparing individual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p<0.001); specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01); specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively. CONCLUSIONS: In children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering.

The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule release and better mimicking the complex properties of the brain tissue. Here, we develop and characterize a drug delivery system for brain repair where MSCs and GDNF are included in a nanoparticle-modified supramolecular guest-host HA HG. In this system, the nanoparticles act as both carriers for the GDNF and active physical crosslinkers of the HG. The multifunctional HG is mechanically compatible with brain tissue and easily injectable. It also protects GDNF from degradation and achieves its controlled release over time. The cytocompatibility studies show that the developed biomaterial provides a friendly environment for MSCs and presents good compatibility with PC12 cells. Finally, using RNA-sequencing (RNA-seq), we investigated how the three-dimensional (3D) environment, provided by the nanostructured HG, impacted the encapsulated cells. The transcriptome analysis supports the beneficial effect of including MSCs in the nanoreinforced HG. An enhancement in the anti-inflammatory effect of MSCs was observed, as well as a differentiation of the MSCs toward a neuron-like cell type. In summary, the suitable strength, excellent self-healing properties, good biocompatibility, and ability to boost MSC regenerative potential make this nanoreinforced HG a good candidate for drug and cell administration to the brain.

Functional diversity regulates the effects of habitat degradation on biocrust phylogenetic and taxonomic diversities.

Biocrusts are major contributors to dryland diversity, functioning, and services. However, little is known about how habitat degradation will impact multiple facets of biocrust diversity and measurable functional traits. We evaluated changes in taxonomic, functional, and phylogenetic diversity of biocrust-forming lichens along a habitat degradation gradient related to the presence of linear infrastructure (i.e., a road) and a profound agricultural driven transformation. To do so, we selected 50 remnants of a Mediterranean shrubland. We considered several surrogates of habitat quality and causal disturbance on the various diversity facets of biocrusts by using structural equation modeling, hypothesizing that habitat degradation primarily affects functional diversity, which in turn regulates changes in taxonomic and phylogenetic diversities, and also that taxonomic and phylogenetic diversities are coupled. Fragment connectivity, distance to linear infrastructure (i.e., a road) and, particularly, soil fertility (i.e., soil P concentration), had mostly negative effects on biocrust functional diversity, which in turn affected both taxonomic and phylogenetic diversities. However, we found no direct effects of habitat degradation variables on the taxonomic and phylogenetic diversities. We also found that increases in phylogenetic diversity had a positive effect on taxonomic diversity along the habitat degradation gradient. Our results indicate that functional diversity of biocrusts is strongly affected by habitat degradation, which may profoundly alter their contribution to ecosystem functioning and services. Furthermore, functional diversity regulates the response of biocrust taxonomic and phylogenetic diversity to habitat degradation. These findings indicate that habitat degradation alters and simplifies the diversity of functional traits of biocrust-forming lichens, leading to biodiversity loss, with important consequences for the conservation of global drylands biodiversity.

Phylogeography of a gypsum endemic plant across its entire distribution range in the western Mediterranean.

PREMISE: Gypsum soils in the Mediterranean Basin house large numbers of edaphic specialists that are adapted to stressful environments. The evolutionary history and standing genetic variation of these taxa have been influenced by the geological and paleoclimatic complexity of this area and the long-standing effect of human activities. However, little is known about the origin of Mediterranean gypsophiles and the factors affecting their genetic diversity and population structure. METHODS: Using phylogenetic and phylogeographic approaches based on microsatellites and sequence data from nuclear and chloroplast regions, we evaluated the divergence time, genetic diversity, and population structure of 27 different populations of the widespread Iberian gypsophile Lepidium subulatum throughout its entire geographic range. RESULTS: Lepidium subulatum diverged from its nearest relatives ~3 million years ago, and ITS and psbA/matK trees supported the monophyly of the species. These results suggest that both geological and climatic changes in the region around the Plio-Pleistocene promoted its origin, compared to other evolutionary processes. We found high genetic diversity in both nuclear and chloroplast markers, but a greater population structure in the chloroplast data. These results suggest that while seed dispersal is limited, pollen flow may be favored by the presence of numerous habitat patches that enhance the movement of pollinators. CONCLUSIONS: Despite being an edaphic endemic, L. subulatum possesses high genetic diversity probably related to its relatively old age and high population sizes across its range. Our study highlights the value of using different markers to fully understand the phylogeographic history of plant species.

Antibacterial and Antifungal Activity of the Human Endometrial Fluid during the Natural Cycle.

Purpose: Some microbiota patterns have been associated with favorable IVF prognosis and others with pathological conditions. The endometrial fluid aspirate (EFA) contains antibacterial proteins that are enriched in implantative IVF cycles, but the antimicrobial effect of EFA has not been addressed. We aimed to evaluate the antimicrobial activity of the human endometrial fluid during the natural cycle. Methods: EFA was obtained through an embryo transfer catheter in 38 women, aged 18-40 years, with regular cycles attending to a fertility clinic. The antimicrobial activity of EFAs was tested against two strains of Staphylococcus aureus; one strain each of Streptococcus agalactiae, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae; and three yeasts (Candida albicans, Candida glabrata, and Candida krusei). Results: All samples exhibited antibacterial activity against S. aureus. In addition, 32.4% of EFAs were active against one of the other microorganisms assayed, 16.2% against two, and 5.4% against four of them. In contrast, none exhibited antibacterial activity against E. coli or K. pneumoniae. The antimicrobial activity differs considerably between EFA samples, and we failed to observe a cycle-related pattern. Conclusions: EFA presented two antimicrobial activity patterns: (a) one common to all the samples, exhibiting activity against S. aureus and lack of activity against E. coli and K. pneumoniae, and (b) an individualized pattern, showing activity against some of the other microorganisms tested. The intensity of antibacterial activity differs between EFA samples. Our data suggest that the uterine microbiota is controlled by means of endometrial fluid components.

Intracervical double-balloon catheter versus dinoprostone for cervical ripening in labor induction in pregnancies with a high risk of uterine hyperstimulation.

PURPOSE: There are numerous methods for cervical ripening although not all of them are indicated in women presenting a higher risk of uterine hyperstimulation. To compare the efficacy and security of the two methods for cervical ripening in the induction of labor in these pregnancies. METHODS: Retrospective analysis of two cohorts consisting of pregnant women who gave birth from 2016 to 2019 (112 inductions with dinoprostone and 112 with intracervical double- balloon). RESULTS: There are statistically significant differences in favor of dinoprostone in deliveries that occurred before 12 h since the start of the induction (28.6% vs 13.4%, p = 0.005) and a higher rate of cervical ripening (55.4% vs 33.9%; p = 0.001). There were no statistically significant differences in induction time, the percentage of women delivering within 24 h or beyond, nor in the type of delivery. Additionally, a decreased need of oxytocin (60.7% vs 42.9%; p = 0.001) and a lower dose when used has been observed in the dinoprostone group. However, Dinoprostone also has a higher rate of minor maternal complications as uterine hyperstimulation (18.8% vs 3.6%; p = 0.001) and altered cardiotocography (26.8% vs 4.5%; p = 0.001). No significant difference has been found between the two groups regarding severe complications. CONCLUSIONS: Dinoprostone presents a greater efficacy for cervical ripening and delivery in ≤ 12 h, with less need of oxytocin perfusion than inductions using an intracervical double-balloon. There is no significant difference in severe maternal complications between the two groups. In conclusion, Dinoprostone could be an effective and safe option for patients at risk of uterine hyperstimulation.

The impact of vascular burden on behavioural and psychological symptoms in older adults with dementia: the BEVASDE study.

OBJECTIVES: Behavioural and psychological symptoms (BPS) worsen quality of life and increase institutionalization in dementia, but the relationship between BPS and vascular burden on neuroimaging is unclear. Our aim is to explore whether the profile of BPS differs between patients with large-vessel or cortical vascular dementia (cVaD), small-vessel or subcortical vascular dementia (sVaD) and Alzheimer's disease (AD). METHODS: The BEVASDE study comprised 806 demented patients (cVaD-136, sVaD-184, AD-486) recruited from outpatient consultations in Salamanca and Avila, Spain. The Clinical Dementia Rating Scale (CDR) and the 12-item Neuropsychiatric Inventory (NPI) were used to evaluate dementia severity and BPS. RESULTS: BPS were reported in 98.5%, 97.3% and 96.9% of the cVaD, sVaD and AD cases, respectively. The median NPI score was 36 in both cVaD and sVaD and 34 in AD, with a median number of four symptoms per patient. The most frequent disorders were depression (64.4%), apathy (61.8%) and sleep disturbance (60.5%). Multivariate regression analyses after controlling for possible confounders showed a higher risk of euphoria (p = 0.011), apathy (p = 0.007), irritability (p = 0.002) and sleep disturbance (p = 0.020) in cVaD than in AD and more apathy (p = 0.0001) and irritability (p = 0.0001) in sVaD than in AD. In contrast, AD subjects had a higher risk of delusions (p = 0.007) and hallucinations (p = 0.023) than patients with cVaD as well as more aberrant motor behaviour than both cVaD (p = 0.0001) and sVaD (p = 0.003). CONCLUSION: BPS are common in dementia and may help in differential diagnosis of the various subtypes. We should inquire about them and treat as necessary.

Automatic Irrigation Scheduling on a Hedgerow Olive Orchard Using an Algorithm of Water Balance Readjusted with Soil Moisture Sensors.

Recent technological advances have made possible automated irrigation scheduling using decision-support tools. These tools help farmers to make better decisions in the management of their irrigation system, thus increasing yields while preserving water resources. The aim of this study is to evaluate in a commercial plot an automated irrigation system combined with remote-sensing techniques and soil mapping that allows the establishment of regulated deficit irrigation (RDI) strategies. The study was carried out over 3 years (2015-2017) in a commercial hedgerow olive orchard of the variety 'Arbequina' located in Alvarado (Extremadura, Spain). An apparent electrical conductivity (ECa) map and a normalized difference vegetation index (NDVI) map were generated to characterize the spatial variability of the plot and classify the zones in homogeneous areas. Then, reference points were selected to monitor the different irrigation sectors. In 2015, the plot was irrigated according to the farmer's technical criteria throughout the plot. In 2016 and 2017, two different areas of the plot were irrigated applying an RDI strategy, one under expert supervision and the other automatically. The results show that in a heterogeneous plot the use of new technologies can be useful to establish the ideal location for an automatic irrigation system. Furthermore, automatic irrigation scheduling made it possible to establish an RDI strategy recommended by an expert, resulting in the homogenization of production throughout the plot without the need for human intervention.

Evaluation of Three Methods for CPR Training to Lifeguards: A Randomised Trial Using Traditional Procedures and New Technologies.

Background and objectives: When the drowning timeline evolves and drowning occurs, the lifeguard tries to mitigate the event by applying the last link of the drowning survival chain with the aim of treating hypoxia. Quality CPR (Cardiopulmonary Resuscitation) and the training of lifeguards are the fundamental axes of drowning survival. Mobile applications and other feedback methods have emerged as strong methods for the learning and training of basic CPR in the last years so, in this study, a randomised clinical trial has been carried out to compare the traditional method as the use of apps or manikins with a feedback system as a method of training to improve the quality of resuscitation. Materials and Methods: The traditional training (TT), mobile phone applications (AP) and feedback manikins (FT) are compared. The three cohorts were subsequently evaluated through a manikin providing feedback, and a data report on the quality of the manoeuvres was obtained. Results: Significant differences were found between the traditional manikin and the manikin with real-time feedback regarding the percentage of compressions with correct depth (30.8% (30.4) vs. 68.2% (32.6); p = 0.042). Hand positioning, percentage correct chest recoil and quality of compressions exceeded 70% of correct performance in all groups with better percentages in the FT (TT vs. FT; p < 0.05). Conclusions: As a conclusion, feedback manikins are better learning tools than traditional models and apps as regards training chest compression. Ventilation values are low in all groups, but improve with the feedback manikin.

Therapeutic Opportunities in Neuroblastoma Using Nanotechnology.

Neuroblastoma (NB) is the most common extracranial solid tumor preferentially occurring in preschoolers. Its characteristic aggressiveness and heterogeneous clinical behavior are especially visible in relapsed or refractory cases and hamper therapeutic success. Although the introduction of novel antitumor agents, such as dinutuximab, isotretinoin, irinotecan, or I-131- metaiodobenzylguanidine, has increased survival rates, the situation in high-risk NB remains dismal. Moreover, treatment is particularly aggressive in these patients, leading to short- and long-term toxicities. The extensive research performed using nanotechnology in recent decades has prompted its application as a therapeutic alternative to overcome some of the common limitations of conventional chemotherapy. Nevertheless, the therapeutic role of nanomedicine in pediatric tumors like NB is not fully elucidated, and to date, only albumin-bound paclitaxel nanoparticles have reached clinic stages. In this review, we summarize the current therapeutic strategies for NB with special attention to the use of nanomedicine. We also highlight the preclinical studies on passive and active targeting nanodelivery of therapeutics in experimental NB models.

Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are a promising cell source for cardiac repair after myocardial infarction (MI) because they offer several advantages such as potential to remuscularize infarcted tissue, integration in the host myocardium, and paracrine therapeutic effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles (MPs) could enhance long-term cell survival and retention in the heart and consequently improve cardiac repair. CMs were obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic poly(lactic-co-glycolic acid) MPs covered with collagen and poly(d-lysine). The potential of the system to support cell survival was analyzed in vitro, demonstrating a 1.70-fold and 1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI model. Interestingly, 2 months after administration, transplanted hiPSC-CMs could be detected in the peri-infarct area. These cells not only maintained the cardiac phenotype but also showed in vivo maturation and signs of electrical coupling. Importantly, cardiac function was significantly improved, which could be attributed to a paracrine effect of cells. These findings suggest that MPs represent an excellent platform for cell delivery in the field of cardiac repair, which could also be translated into an enhancement of the potential of cell-based therapies in other medical applications.

Cycloaddition of Nitrile Oxides to Graphene: a Theoretical and Experimental Approach.

Density functional theory (DFT) studies of the interaction between graphene sheets and nitrile oxides have proved the feasibility of the reaction through 1,3-dipolar cycloaddition. The viability of the approach has been also confirmed experimentally through the cycloaddition of few-layer exfoliated graphene and nitrile oxides containing functional organic groups with different electronic nature. The cycloaddition reaction has been successfully achieved in one-pot from the corresponding oximes under microwave (MW) irradiation. The successful formation of the isoxazoline ring has been confirmed by Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS).

One-year bleaching efficacy using two HP products with different pH: A double-blind randomized clinical trial.

OBJECTIVES: This split-mouth, double-blind, randomized clinical trial evaluated the 1-year bleaching efficacy produced by two hydrogen peroxide gels with different pHs. MATERIALS AND METHODS: Twenty-eight patients were divided into two groups corresponding to two different products: Pola Office (pH = 2.0/SDI) and Pola Office Plus (pH = 7.0/SDI). The treatment was assessed during and after the bleaching procedure up to 12 months post-treatment. The assessment consisted of two bleaching scales shade guide units (ΔSGU) and spectrophotometric device (ΔE, ΔE00, and Whiteness Index) of both maxillary quadrants. Results for ΔSGUs in both scales and ΔE00 and Whiteness Index were compared using Mann Whitney test and ΔE measurements through the t-Student test for paired samples in each evaluation time. The color rebound (1- vs 12-month postbleaching data) was evaluated with Wilcoxon test (alpha = .05). RESULTS: During the different times of evaluation, the color variation was similar for both products (P > .05), both for subjective (ΔSGUs) and objective assessments (ΔE, ΔE00, and Whiteness Index). Also, both products showed a slight rebound after 12-month postbleaching (P > .05). CONCLUSIONS: Concerning the stability of color, in-office dental whitening with two hydrogen peroxide gels of different pHs produced similar results, with no significant of regression, for 12 months postwhitening. CLINICAL SIGNIFICANCE: Bleaching using a neutral (pH = 7.0) in-office gel demonstrated similar stability and rebound effect than an acidic one (pH = 2.0).

The Role of Religion and Religiosity in Alcohol Consumption in Adolescents in Spain.

This study explored the relationship between religion, religiosity and alcohol consumption in a sample of 2.890 adolescents (ages 12-18) in Madrid, Spain. Results showed that non-believers were the group that consume and abuse alcohol the most, as opposed to Catholics. Besides, religiosity was related to a lower alcohol use. Therefore, religion and religiosity in Spanish adolescents appear to be related to a low alcohol use. This contribution may help to clarify the risk and protection factors for alcohol consumption by adolescents and contribute to strengthening the preventive actions.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.