Urea and glucose modulation during freezing exposure in three temperate frogs reveals specific targets in relation to climate.

Amphibian diversity is most prominent in the warm and humid tropical and subtropical regions across the globe. Nonetheless, amphibians also inhabit high-altitude tropical mountains and regions at medium and high latitudes, exposing them to subzero temperatures and requiring behavioural or physiological adaptations to endure freezing events. While freeze tolerance has been predominantly reported in high-latitude zones where species endure prolonged freezing (several weeks or months), less is known about mid-latitudes amphibians exposed to occasional subzero temperatures. In this study, we employed a controlled ecological protocol, subjecting three frog species from the Iberian Peninsula (Rana parvipalmata, Epidalea calamita, and Pelobates cultripes) to a 2-h exposure to temperatures of -2 °C to investigate the accumulation of urea and glucose as physiological mechanisms associated with survival at freezing temperatures. Our results revealed a moderate response in the production of cryoprotectant metabolites under experimental freezing conditions, particularly urea, with notable findings in R. parvipalmata and E. calamita and no response in P. cultripes. However, no significant alterations in glucose concentrations were observed in any of the studied frog species. This relatively weak freezing tolerance response differs from the strong response exhibited by amphibians inhabiting high latitudes and enduring prolonged freezing conditions, suggesting potential reliance on behavioural adaptations to cope with occasional freezing episodes.

The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease.

Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with a poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including CPAMD8 and ADAMTSL4, compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of adamtsl4 and cpamd8 zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinase-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.

Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial.

OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.

Decay kinetics of HIV-1-RNA in seminal plasma with dolutegravir/lamivudine versus dolutegravir plus emtricitabine/tenofovir alafenamide in treatment-naive people living with HIV.

BACKGROUND: This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. METHODS: Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. RESULTS: Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30-5.43) and 4.76 (4.09-5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). CONCLUSIONS: After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.

Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-year-old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.

A Low-Cost Non-Intrusive Method for In-Field Motor Speed Measurement Based on a Smartphone.

Induction motors are broadly used as drivers of a large variety of industrial equipment. A proper measurement of the motor rotation speed is essential to monitor the performance of most industrial drives. As an example, the measurement of rotor speed is a simple and broadly used industrial method to estimate the motor's efficiency or mechanical load. In this work, a new low-cost non-intrusive method for in-field motor speed measurement, based on the spectral analysis of the motor audible noise, is proposed. The motor noise is acquired using a smartphone and processed by a MATLAB-based routine, which determines the rotation speed by identifying the rotor shaft mechanical frequency from the harmonic spectrum of the noise signal. This work intends to test the hypothesis that the emitted motor noise, like mechanical vibrations, contains a frequency component due to the rotation speed which, to the authors' knowledge, has thus far been disregarded for the purpose of speed measurement. The experimental results of a variety of tests, from no load to full load, including the use of a frequency converter, found that relative errors on the speed estimation were always lower than 0.151%. These findings proved the versatility, robustness, and accuracy of the proposed method.

Null cyp1b1 Activity in Zebrafish Leads to Variable Craniofacial Defects Associated with Altered Expression of Extracellular Matrix and Lipid Metabolism Genes.

CYP1B1 loss of function (LoF) is the main known genetic alteration present in recessive primary congenital glaucoma (PCG), an infrequent disease characterized by delayed embryonic development of the ocular iridocorneal angle; however, the underlying molecular mechanisms are poorly understood. To model CYP1B1 LoF underlying PCG, we developed a cyp1b1 knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries the c.535_667del frameshift mutation that results in the 72% mRNA reduction with the residual mRNA predicted to produce an inactive truncated protein (p.(His179Glyfs*6)). Microphthalmia and jaw maldevelopment were observed in 23% of F0 somatic mosaic mutant larvae (144 hpf). These early phenotypes were not detected in cyp1b1-KO F3 larvae (144 hpf), but 27% of adult (four months) zebrafish exhibited uni- or bilateral craniofacial alterations, indicating the existence of incomplete penetrance and variable expressivity. These phenotypes increased to 86% in the adult offspring of inbred progenitors with craniofacial defects. No glaucoma-related phenotypes were observed in cyp1b1 mutants. Transcriptomic analyses of the offspring (seven dpf) of cyp1b1-KO progenitors with adult-onset craniofacial defects revealed functionally enriched differentially expressed genes related to extracellular matrix and cell adhesion, cell growth and proliferation, lipid metabolism (retinoids, steroids and fatty acids and oxidation-reduction processes that include several cytochrome P450 genes) and inflammation. In summary, this study shows the complexity of the phenotypes and molecular pathways associated with cyp1b1 LoF, with species dependency, and provides evidence for the dysregulation of extracellular matrix gene expression as one of the mechanisms underlying the pathogenicity associated with cyp1b1 disruption.

A data mining based clinical decision support system for survival in lung cancer.

BACKGROUND: A clinical decision support system (CDSS ) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. MATERIALS AND METHODS: Prospective multicenter data from 543 consecutive (2013-2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. RESULTS: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). CONCLUSIONS: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients' features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.

Commentary: Ultraviolet radiation triggers "preparation for oxidative stress" antioxidant response in animals: Similarities and interplay with other stressors.

Preparation for oxidative stress (POS), i.e., the upregulation of endogenous antioxidants, is a widespread response of animals exposed to extreme conditions. This response has been described for more than 80 animal species belonging to eight phyla during hypometabolism or situations that limit oxygen availability. The pattern of the typical POS-response, in which a mild redox imbalance triggers antioxidant adjustments that results in increased tolerance to subsequent oxidative insults, roughly follows the curve of hormetic phenomena. A similar pattern has been reported for various animal species exposed to ultraviolet radiation (UVR) - these studies, on animals from six phyla, are discussed herein. In the light of the similarities in the redox-response of animals exposed to either oxygen restriction or UVR, we argue in this essay that UVR elicits a type of response that fits the POS theory. Exposure to UVR induces both reactive species formation and antioxidant adaptation, which is the essence of typical POS-responses. Thus, antioxidant response to UVR in animals can be categorized as a POS-type mechanism. Moreover, considering that animals are exposed to multiple stressors simultaneously in nature, this would represent an ecologically relevant process, by which one stressor (e.g., UV or ionizing radiation) may enhance the tolerance to other. We also discuss a possible role of low doses of ionizing radiation as inductor of POS-like responses in animals.

Effects of Cross-Clamping on Vascular Mechanics: Comparing Waveform Analysis With a Numerical Model.

BACKGROUND: Immediate changes in vascular mechanics during aortic cross-clamping remain widely unknown. By using a numerical model of the arterial network, vascular compliance and resistance can be estimated and the time constant of pressure waves can be calculated and compared with results from the classic arterial waveform analysis. METHODS: Experimental data were registered from continuous invasive radial artery pressure measurements from 11 patients undergoing vascular surgery. A stable set of beats were chosen immediately before and after each clamping event. Through the arterial waveform analysis, the time constant was calculated for each individual beat and for a mean beat of each condition as to compare with numerical simulations. Overall proportional changes in resistance and compliance during clamping and unclamping were calculated using the numerical model. RESULTS: Arterial waveform analysis of individual beats indicated a significant 10% median reduction in the time constant after clamping, and a significant 17% median increase in the time constant after unclamping. There was a positive correlation between waveform analysis and numerical values of the time constant, which was moderate (ρ = 0.51; P = 0.01486) during clamping and strong (ρ = 0.77; P ≤ 0.0001) during unclamping. After clamping, there was a significant 16% increase in the mean resistance and a significant 23% decrease in the mean compliance. After unclamping, there was a significant 19% decrease in the mean resistance and a significant 56% increase in the mean compliance. CONCLUSIONS: There are significant hemodynamic changes in vascular compliance and resistance during aortic clamping and unclamping. Numerical computer models can add information on the mechanisms of injury due to aortic clamping.

Enabling the Orchestration of IoT Slices through Edge and Cloud Microservice Platforms.

This article addresses one of the main challenges related to the practical deployment of Internet of Things (IoT) solutions: the coordinated operation of entities at different infrastructures to support the automated orchestration of end-to-end Internet of Things services. This idea is referred to as "Internet of Things slicing" and is based on the network slicing concept already defined for the Fifth Generation (5G) of mobile networks. In this context, we present the architectural design of a slice orchestrator addressing the aforementioned challenge, based on well-known standard technologies and protocols. The proposed solution is able to integrate existing technologies, like cloud computing, with other more recent technologies like edge computing and network slicing. In addition, a functional prototype of the proposed orchestrator has been implemented, using open-source software and microservice platforms. As a first step to prove the practical feasibility of our solution, the implementation of the orchestrator considers cloud and edge domains. The validation results obtained from the prototype prove the feasibility of the solution from a functional perspective, verifying its capacity to deploy Internet of Things related functions even on resource constrained platforms. This approach enables new application models where these Internet of Things related functions can be onboarded on small unmanned aerial vehicles, offering a flexible and cost-effective solution to deploy these functions at the network edge. In addition, this proposal can also be used on commercial cloud platforms, like the Google Compute Engine, showing that it can take advantage of the benefits of edge and cloud computing respectively.

Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy.

AIM: The purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients. BACKGROUND: Previous hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT. MATERIALS AND METHODS: We evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04 Gy at 2.52 Gy/fraction (N = 25; 66%), 70 Gy at 2.5 Gy/fraction (N = 4; 11%) and 70.2 Gy at 2.6 Gy/fraction (N = 9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Median age at diagnosis was 70 years (range 49-80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P = 0.025). Patients with PSA ≤8 (P = 0.048) or comorbidities (P = 0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P = 0.028). CONCLUSIONS: Hypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.

D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis.

BACKGROUND: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT. METHODS: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence. RESULTS: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7). CONCLUSIONS: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.

Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.

Safety and effectiveness of cantharidin-podophylotoxin-salicylic acid in the treatment of recalcitrant plantar warts.

The aim of our study was to evaluate the efficacy and safety of topical cantharidin-podophylotoxin-salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013. A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow-up visit or telephone call after treatment and were included in this study. Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty-four patients required one application to eliminate the wart and 21 patients required two applications/patient. Seventy-seven percent of patients experienced blistering - an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding. All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment.

Thermal ecology of montane Atelopus (Anura: Bufonidae): A study of intrageneric diversity.

Harlequin frogs (Bufonidae: Atelopus) are among the most threatened frog genus in the world and reach very high elevations in the tropical Andes and the Sierra Nevada de Santa Marta (SNSM). Learning about their thermal ecology is essential to infer sensitivity to environmental changes, particularly climate warming. We report on the activity temperature and thermoregulatory behavior of three high-elevation species of harlequin frogs, Atelopus nahumae, Atelopus laetissimus and Atelopus carrikeri. The first two mentioned live in streams in Andean rain forests, whereas A. carrikeri inhabits paramo streams in the SNSM. We studied the thermal ecology of these species in tree localities differing in altitude, and focused on activity body, operative, substrate and air temperature. A main trend was lower body temperature as elevation increased, so that differences among species were largely explained by differences in substrate temperature. However, this temperature variation was much lower in forest species than paramo species. The Atelopus species included in this work proved to be thermoconformers, a trend that not extended to all congenerics at high elevation. This diversity in thermal ecology poses important questions when discussing the impact of climate warming for high-elevation harlequin frogs. For example, forest species show narrow thermal ranges and, if highly specialized, may be more susceptible to temperature change. Paramo species such as A. carrikeri, in contrast, may be more resilient to temperature change.

Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn(2+) and Mg (2+).

Strontium ranelate (SR) is an orally administered and bone-targeting anti-osteoporotic agent that increases osteoblast-mediated bone formation while decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral and femoral bone fractures in postmenopausal women with osteoporosis. Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process of bone formation and osteoid mineralization. In this study we investigated the direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from UMR106 osteosarcoma cells, as well as its possible interactions with the divalent cations Zn(2+) and Mg(2+). In the presence of Mg(2+), both SR and SrCl2 (0.05-0.5 mM) significantly increased ALP activity (15-66 % above basal), and this was dose-dependent in the case of SR. The stimulatory effect of strontium disappeared in the absence of Mg(2+). The cofactor Zn(2+) also increased ALP activity (an effect that reached a plateau at 2 mM), and co-incubation of 2 mM Zn(2+) with 0.05-0.5 mM SR showed an additive effect on ALP activity stimulation. SR induced a dose-dependent decrease in the Km of ALP (and thus an increase in affinity for its substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn(2+) further decreased Km in all cases. These direct effects of SR on osteoblastic ALP activity could be indicating an alternative mechanism by which this compound may regulate bone matrix mineralization.

[Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report]. / Neurocitoma atípico de cerebelo que simula un hemangioblastoma. Presentación de un caso.

Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence.

[Workload measurement scales to severe burn patient]. / Escalas de medida de cargas de trabajo en el paciente gran quemado.

To provide human resources appropriately in a unit is necessary to have measurement scales that assess workloads most accurate as possible. In this article, we have review in various databases most used scales and have found the lack of a specific scale for burn patients. Within clinical practice, burned patient is included in "critical patient" category, so the workloads evaluation uses validated scales for intensive care units (ICU). But the burn patient, in addition to the care of a critically ill patient themselves, requires a series of specific care that consume a lot of time nursing. In order to find a manpower use score that fit as much as possible the characteristic nurse activity in a burns units (UGQ), there has been a description of the used scales in critical patients and we propose the most important aspects to be included in a future specific scale for severe burns.