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Background. Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. Objectives. To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. Methods. Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. Results. The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p=0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p=0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p=0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p=0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. Conclusion. HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.

Background. Acute kidney injury occurs in approximately 20% of hospitalized cirrhotic patients. Mortality is estimated at 60% within a month and 65% within a year. Aims. To evaluate survival in 30 days and in 3 months of cirrhotic patients hospitalized with acute kidney injury, identifying factors associated with mortality. Methods. 52 patients with cirrhosis admitted to an academic tertiary center who presented acute kidney injury according to the International Club of Ascites criteria were evaluated. Clinical and laboratory data was collected at diagnosis between 2011 and 2015. Results. Average age was 54.6 (±10.7) years and 69.2% were male. The average MELD, MELD-Na, and Child-Pugh scores were 21.9 (±7.0), 24.5 (±6.7), and 10.1 (±2.2), respectively. Thirty patients (57.7%) were in acute kidney injury stage 1, 16 (30.8%) in stage 2, and six (11.6%) in stage 3. Mortality was 28.6% in 30 days and 44.9% in three months. In multivariate analysis, variables that were associated independently to mortality were lack of response to expansion treatment and Child-Pugh score. Mortality was 93.3% in three months among nonresponders compared to 28.6% among those who responded to volume expansion (p

Osteoporosis represents an imbalance between bone formation and bone resorption. As a result of low estrogen levels, it is markedly prevalent during menopause, thus making such patients susceptible to fractures. Both bone formation and resorption are modulated by nitric oxide (NO). Currently, there are no risk-free pharmaceutical prevention therapies for osteoporosis. COMB-4, a nutraceutical combination of Paullinia cupana, Muira puama, ginger, and L-citrulline, known to activate the NO-cGMP pathway, was reported to accelerate fracture healing in the rat. To determine whether COMB-4 could be effective in preventing menopausal osteoporosis, it was compared to estradiol (E2) in an ovariectomized (OVX) rat osteoporosis model. Nine-month-old female Sprague Dawley rats were divided into SHAM, OVX, OVX+E2, and OVX+COMB-4. After 100 days of treatment, bone mineral density (BMD) and bone mineral content (BMC) were measured by DXA scan. TRAP staining was performed in the femur and lumbar vertebrae. TRACP 5b and osteocalcin levels were assayed in the serum. MC3T3-E1 cells were differentiated into osteoblasts and treated with COMB-4 for one week in order to evaluate calcium deposition by Alizarin staining, cGMP production by ELISA, and upregulation of the nitric oxide synthase (NOS) enzymes by RT-PCR. OVX resulted in a decrease in BMD, BMC, and serum osteocalcin and an increase in serum TRACP 5b. Except for an increase in BMC with COMB-4, both E2 and COMB-4 reverted all bone and serum markers, as well as the number of osteoclasts in the vertebrae, to SHAM levels. Incubation of MC3T3-E1 cells with COMB-4 demonstrated an increase in the three NOS isoforms, cGMP, and calcium deposition. COMB-4 increased BMD in OVX rats by inhibiting bone resorption and increasing calcium deposition presumably via activation of the NO-cGMP pathway. It remains to be determined whether COMB-4 could be a potential nutraceutical therapy for the prevention of premenopausal bone loss.

Introduction. Liver diseases influence musculoskeletal functions and may negatively affect the exercise capacity of patients with cirrhosis. Aim. To test the relationship between the six-minute walk test (6MWT), maximal inspiratory pressure (MIP), and exercise capacity (VO2peak) measures and the survival rate of patients with cirrhosis. Methods. This prospective cohort study consisted of 86 patients diagnosed with cirrhosis with the following aetiology: hepatitis C virus (HCV), hepatitis B virus (HBV), and/or alcoholic cirrhosis (AC). All patients were followed up for three years and submitted to the 6MWT, pressure measurements with a compound gauge, and an exercise test (VO2peak). Results. The survival analysis showed that the individuals who covered a distance shorter than 410 m during the 6MWT had a survival rate of 55% compared with a rate of 97% for the individuals who walked more than 410 m (p = 0.0001). Individuals with MIPs below −70 cmH2O had a survival rate of 62% compared with a rate of 93% for those with MIPs above −70 cmH2O (p = 0.0001). The patients with values below 17 mL/kg had a survival rate of 55% compared with a rate of 94% for those with values above 17 mL/kg (p = 0.0001). Conclusion. The 6MWT distance, MIP, and oxygen consumption are predictors of mortality in patients with cirrhosis.

Turbulence and aircraft icing associated with mountain waves are weather phenomena potentially affecting aviation safety. In this paper, these weather phenomena are analysed in the vicinity of the Adolfo Suárez Madrid-Barajas Airport (Spain). Mountain waves are formed in this area due to the proximity of the Guadarrama mountain range. Twenty different weather research and forecasting (WRF) model configurations are evaluated in an initial analysis. This shows the incompetence of some experiments to capture the phenomenon. The two experiments showing the best results are used to simulate thirteen episodes with observed mountain waves. Simulated pseudosatellite images are validated using satellite observations, and an analysis is performed through several skill scores applied to brightness temperature. Few differences are found among the different skill scores. Nevertheless, the Thompson microphysics scheme combined with the Yonsei university PBL scheme shows the best results. The simulations produced by this scheme are used to evaluate the characteristic variables of the mountain wave episodes at windward and leeward and over the mountain. The results show that north-northwest wind directions, moderate wind velocities, and neutral or slightly stable conditions are the main features for the episodes evaluated. In addition, a case study is analysed to evidence the WRF ability to properly detect turbulence and icing associated with mountain waves, even when there is no visual evidence available.

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108) will be randomly assigned to either the experimental low dose (n=36), the experimental high dose (n=36), or the comparator arm (n=36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

In the context of aviation weather hazards, the study of aircraft icing is very important because of several accidents attributed to it over recent decades. On February 1, 2012, an unusual meteorological situation caused severe icing of a C-212-200, an aircraft used during winter 2011-2012 to study winter cloud systems in the Guadarrama Mountains of the central Iberian Peninsula. Observations in this case were from a MP-3000A microwave radiometric profiler, which acquired atmospheric temperature and humidity profiles continuously every 2.5 minutes. A Cloud Aerosol and Precipitation Spectrometer (CAPS) was also used to study cloud hydrometeors. Finally, ice nuclei concentration was measured in an isothermal cloud chamber, with the goal of calculating concentrations in the study area. Synoptic and mesoscale meteorological conditions were analysed using the Weather Research and Forecasting (WRF) model. It was demonstrated that topography influenced generation of a mesolow and gravity waves on the lee side of the orographic barrier, in the region where the aircraft experienced icing. Other factors such as moisture, wind direction, temperature, atmospheric stability, and wind shear were decisive in the appearance of icing. This study indicates that icing conditions may arise locally, even when the synoptic situation does not indicate any risk.

Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system.

In recent decades, a decrease in snowfall attributed to the effects of global warming (among other causes) has become evident. However, it is reasonable to investigate meteorological causes for such decrease, by analyzing changes in synoptic scale patterns. On the Iberian Peninsula, the Castilla y León region in the northwest consists of a central plateau surrounded by mountain ranges. This creates snowfalls that are considered both an important water resource and a transportation risk. In this work, we develop a classification of synoptic situations that produced important snowfalls at observation stations in the major cities of Castilla y León from 1960 to 2011. We used principal component analysis (PCA) and cluster techniques to define four synoptic patterns conducive to snowfall in the region. Once we confirmed homogeneity of the series and serial correlation of the snowfallday records at the stations from 1960 to 2011, we carried out a Mann-Kendall test. The results show a negative trend at most stations, so there are a decreased number of snowfall days. Finally, variations in these meteorological variables were related to changes in the frequencies of snow events belonging to each synoptic pattern favorable for snowfall production at the observatory locations.

Satellite simulators are used to calculate the brightness temperature Tb that would be measured by a space borne sensor under a set of atmospheric conditions accounting for the radiometric characteristics of the sensor and the orbital parameters of the satellite. In this study, a simple approach is proposed for the parameterization of emissivity over land, a key parameter for the calculation of microwave Tb. The rationale is to simulate a large ensemble of emissivity values for each frequency and surface characteristics and then relate the most likely observed value with soil characteristics. The derived emissivity values are used for the simulation of Tb and simulated radiance is then compared with satellite observations. It is shown that this method improves the simulation of radiance and that it is suitable to provide a first guess of the emissivity value (a prior) that can then be refined using iterative procedures.

The development of ischemic gangrene of the penis following implantation of prosthesis is unusual, and very few cases are available in the literature. As a result, no established treatment protocol is available. We report our experience within a case of gangrene of the glans following implantation of a three-component prosthesis. We present a 53-year-old male, smoker with diabetes and hypercholesterolemia, who underwent surgery for the insertion of a penile prosthesis with 3 components to correct his erectile dysfunction and severe Peyronie's disease. The procedure was carried out without incidents. During the postoperative period, the patient began to complain from penile and perineal pain. He developed avascular necrosis of the glans. The necrosed area was excised. Four weeks later, he developed fever and perineal pain arriving to the emergency room with the prosthesis extruding through the glans. He had emergency surgery to remove the prosthesis plus surgical lavage and was prescribed broad-spectrum antibiotic therapy. Four weeks later, the penis was completely revascularized and reepithelialized. Ischemic gangrene following penile prosthesis implantation takes place in patients with poor peripheral vascularisation. Diabetes mellitus has been the common denominator to all of the reported cases.

Hail precipitation is characterized by enhanced spatial and temporal variability. Association Nationale d’Etude et de Lutte contre les Fléaux Atmosphériques (ANELFA) installed hailpad networks in the Atlantic and Midi-Pyrénées regions of France. Historical data of hail variables from 1990 to 2010 were used to characterize variability. A total of 443 stations with continuous records were chosen to obtain a first approximation of areas most affected by hail. The Cressman method was selected for this purpose. It was possible to find relationships between spatial distributions of the variables, which are supported by obtained Pearson correlations. Monthly and annual trends were examined using the Mann-Kendall test for each of the total affected hailpads. There were 154 pads with a positive trend; most were located between Tarbes and Saint-Gaudens. We found 177 pads with a negative trend, which were largely south of a pine forest in Landes. The remainder of the study area showed an elevated spatial variability with no pattern, even between relatively close hailpads. A similar pattern was found in Lérida (Spain) and Southeast France. In the entire area, monthly trends were predominantly negative in June, July, and August, whereas May had a positive trend; again, however, there was no spatial pattern. There was a high concentration of hailpads with positive trend near the Pyrenees, probably owing to orographic effects, and if we apply cluster analysis with the Mann-Kendall values, the spatial variability is accentuated for stations at higher altitude.

The aim of this preliminary study was to identify microorganisms with antimicrobial resistance profile and biofilm producers in oropharynx of Rupornis magnirostris and Caracara plancus. Six R. magnirostris and six C. plancus maintained in Triage Center for Wild Animals (CETAS) facilities were studied. Coagulase-positive staphylococci (CoPS), enterobacteria, and yeasts were identified by the biochemical analysis or MALDI-TOF mass spectrometry. The resistance profile of the microorganisms was analyzed according to CLSI. The biofilm production was evaluated by Congo red and violet crystal staining methods. Among the 12 birds, 10 presented strains of CoPS and/or enterobacteria with resistance profile, such as methicillin-resistant CoPS (MR-CoPS), vancomycin-resistant CoPS (VR-CoPS), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), and Klebsiella pneumoniae carbapenemase- (KPC-) producing bacteria. Regards the fungal analysis, Candida spp., Cryptococcus spp., Rhodotorula mucilaginosa, R. glutinis, and Trichosporon coremiiforme were identified. All the Trichosporon coremiiforme strains were resistant to amphotericin B, as well as all the Rhodotorula mucilaginosa exhibited resistance to fluconazole. Related to the biofilm production, among the 8 CoPS, 27 enterobacteria, and 10 yeasts isolates, 3, 16, and 7 strains were biofilm producers, respectively. Thus, the presence of these microorganisms in birds of prey is worrisome, highlighting its possible influence in the spread of infections in urban centers.

Background. Autosomal recessive hereditary spastic paraplegias (HSP) are a rare group of hereditary neurodegenerative disorders characterized by spasticity with or without other symptoms. SPG11 gene is the most common cause of autosomal recessive HSP. We report a case of autosomal recessive spastic paraplegia type 76 due to heterozygous variants of CAPN1 in an Argentinean subject. Case Presentation. A 38-year-old Argentinean female presented with progressive gait problems and instability of 15-year duration. Oculomotor abnormalities, ataxia, bradykinesia, cervical dystonia, and lower limb pyramidal signs were observed. Brain MRI was unremarkable. Whole-exome sequencing analysis identified two heterozygous variants in CAPN1. Conclusions. Clinicians should screen for CAPN1 mutation in a young female patient without significant family history with a spastic paraplegia syndrome associated with other symptoms.