Differences in cardiorespiratory responses in winter mountaineering according to the pathway snow conditions

Locomotion during ascent requires higher energetic consumption than in flat terrain. Efficiency in locomotion decreases in snowy terrain, presumably because of the changes in the biomechanical pattern of walking. This study aims to observe differences in cardiorespiratory responses and energetic expenditure between locomotion in a snowy terrain with an already fixed footstep pathway (FP) and in fresh virgin snow (FS) that has not been previously compacted. 15 volunteers participated in the study, all of them with experience in mountain activities at a competition level, with a regular training regime up to 10 hours a week. Estimated maximal theoretical oxygen consumption showed a mild increase (2,6% CI 95%: 0.9-4.5%, t=3.2, p=0.005) when subjects progressed in FP. Time necessary to complete FS (4 min and 15 sec ± 30 sec) itinerary was longer than for FP (3 min 45 sec ± 29 sec). Uphill walking velocity improved in 0.43 ± 0.11 Km·h-1 (t=4.2 p=0,01) when progressing in CT. Respiratory rate was higher for FS (2.3 ± 2.4 b·min-1, t=4.0 p= 0.001). For a same itinerary, locomotion in snow that has not been compacted before requires more time and represents a higher energetic cost, either at maximal or submaximal intensities. This should be considered in scheduling mountain ascents as part of the safety strategies. Climbing on virgin snow impedes developing maximal aerobic power so athletes must regard the value of strength work of lower limbs to improve performance

Amputation risk factors in severely frostbitten patients

In recent years, the incidence of frostbite has increased among healthy young adults who practice winter sports (skiing, mountaineering, ice climbing and technical climbing/alpinism) at both the professional and amateur levels. Moreover, given that the population most frequently affected is healthy and active, frostbite supposes a substantial interruption of their normal activity and in most cases is associated with long-term sequelae. It particularly has a higher impact when the affected person's daily activities require exposure to cold environments, as either sports practices or work activities in which low temperatures are a constant (ski patrols, mountain guides, avalanche forecasters, workers in the cold chain, etc.). Clinical experience with humans shows a limited reversibility of injuries via potential tissue regeneration, which can be fostered with optimal medical management. Data were collected from 92 frostbitten patients in order to evaluate factors that represent a risk of amputation after severe frostbite. Mountain range, years of expertise in winter mountaineering, time elapsed before rewarming and especially altitude were the most important factors for a poor prognosis

Constitutional mismatch repair deficiency (CMMRD) presenting with high-grade glioma, multiple developmental venous anomalies and malformations of cortical development-a multidisciplinary/multicentre approach and neuroimaging clues to clinching the diagnosis

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter. The tumour was debulked and confirmed to be a HGG on histopathology. The suspected diagnosis of CMMRD was confirmed on immunohistochemistry and genetic testing which revealed mutations in PMS2 and MSH6. The combination of a HGG, multiple DVAs and MCD in a paediatric or young adult patient should prompt the neuroradiologist to suggest an underlying diagnosis of CMMRD. A diagnosis of CMMRD has an important treatment and surveillance implications not only for the child but also the family in terms of genetic counselling

Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder

Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group. © 2021, The Author(s)

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Outcome of children and adolescents with central nervous system tumors in phase I trials

Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials

Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort.

Objectives To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours.Methods Paediatric patients (-2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians.Results The values for ADC, D, DDCα, α, and DDCK gave CV 30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083).Conclusion Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data.Key points • ADC has good repeatability as low 5th centile of the histogram distribution. • High CV was observed for all parameters at extremes of histogram. • Parameters from the stretched exponential model showed low coefficients of variation. • The median ADC, D, DDC α , and DDC K are highly correlated and repeatable. • Perfusion/kurtosis parameters showed high CV variations across their histogram distributions

A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC)

Cosmic-Ray Anisotropies in Right Ascension Measured by the Pierre Auger Observatory

We present measurements of the large-scale cosmic-ray (CR) anisotropies in R.A., using data collected by the surface detector array of the Pierre Auger Observatory over more than 14 yr. We determine the equatorial dipole component, through a Fourier analysis in R.A. that includes weights for each event so as to account for the main detector-induced systematic effects. For the energies at which the trigger efficiency of the array is small, the east-west method is employed. Besides using the data from the array with detectors separated by 1500 m, we also include data from the smaller but denser subarray of detectors with 750 m separation, which allows us to extend the analysis down to ∼0.03 EeV. The most significant equatorial dipole amplitude obtained is that in the cumulative bin above 8 EeV, %, which is inconsistent with isotropy at the 6σ level. In the bins below 8 EeV, we obtain 99% CL upper bounds on d ⊥ at the level of 1%-3%. At energies below 1 EeV, even though the amplitudes are not significant, the phases determined in most of the bins are not far from the R.A. of the Galactic center, at GC =-94°, suggesting a predominantly Galactic origin for anisotropies at these energies. The reconstructed dipole phases in the energy bins above 4 EeV point instead to R.A. that are almost opposite to the Galactic center one, indicative of an extragalactic CR origin

COVID Isolation Eating Scale (CIES): Analysis of the impact of confinement in eating disorders and obesity-A collaborative international study

Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.This manuscript and research was supported by grants from the Ministeriode Economía y Competitividad (PSI2015-68701-R), Instituto de Salud Carlos III (ISCIII) (FIS PI14/00290/ INT19/00046nd PI17/01167) and co-funded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. CIBERobn, CIBERsam and CIBERDEM are all initiatives of ISCIII. GMB is supported by a postdoctoral grant from FUNCIVA. This initiative is supported by Generalitat de Catalunya. LM is supported by a postdoctoral grant of the mexican institution Consejo Nacional de Ciencia y Tecnología (CONACYT). PPM was supported, in part, by a Portuguese Foundation for Science and Technology grant (POCI-01-0145-FEDER-028145). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript