Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

A method to produce a flexible and customized fuel models dataset.

Simulation of vegetation fires very often resorts to fire-behavior models that need fuel models as input. The lack of fuel models is a common problem for researchers and fire managers because its quality depends on the quality/availability of data. In this study we present a method that combines expert- and research-based knowledge with several sources of data (e.g. satellite and fieldwork) to produce customized fuel models maps. Fuel model classes are assigned to land cover types to produce a basemap, which is then updated using empirical and user-defined rules. This method produces a map of surface fuel models as detailed as possible. It is reproducible, and its flexibility relies on juxtaposing independent spatial datasets, depending on their quality or availability. This method is developed in a ModelBuilder/ArcGis toolbox named FUMOD that integrates ten sub-models. FUMOD has been used to map the Portuguese annual fuel models grids since 2019, supporting regional fire risk assessments and suppression decisions. Datasets, models and supplementary files are available in a repository (https://github.com/anasa30/PT_FuelModels). •FUMOD is a flexible toolbox with ten sub-models included that maps updated Portuguese fuel models.

Ba+2 ion trapping using organic submonolayer for ultra-low background neutrinoless double beta detector.

If neutrinos are their own antiparticles the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay can occur. The very long lifetime expected for these exceptional events makes its detection a daunting task. In order to conduct an almost background-free experiment, the NEXT collaboration is investigating novel synthetic molecular sensors that may capture the Ba dication produced in the decay of certain Xe isotopes in a high-pressure gas experiment. The use of such molecular detectors immobilized on surfaces must be explored in the ultra-dry environment of a xenon gas chamber. Here, using a combination of highly sensitive surface science techniques in ultra-high vacuum, we demonstrate the possibility of employing the so-called Fluorescent Bicolor Indicator as the molecular component of the sensor. We unravel the ion capture process for these molecular indicators immobilized on a surface and explain the origin of the emission fluorescence shift associated to the ion trapping.

Thoracoscopic management of congenital esophageal stenosis secondary to tracheobronchial remnant in pediatric patients. / Manejo toracoscópico en estenosis esofágica congénita secundaria a remanente traqueobronquial, en población pediátrica.

INTRODUCTION: Congenital esophageal stenosis (CES) is an extremely rare pathology in children, with an incidence of 1/25,000-50,000 live births. According to its histopathological classification, there are three types of CES: fibromuscular hyperplasia, membranous diaphragm, and tracheobronchial remnants. CLINICAL CASE: We present the clinical case of a 39-month-old male patient diagnosed with CES secondary to tracheobronchial remnants, with multiple vomit and reflux episodes since he was 4 months old. He was admitted at the emergency department with respiratory distress. An upper GI endoscopy and an esophagogram were initially carried out. Stenosis resection and thoracoscopic esophageal anastomosis were performed. CONCLUSIONS: Tracheobronchial remnants are the second most common presentation of congenital esophageal stenosis. They can be managed through dilatations or surgery according to etiology.

INTRODUCCION: La estenosis congénita de esófago es una patología extremadamente rara en niños, con una incidencia de 1/25.000-50.000 nacimientos. Según la clasificación histopatológica se encuentran tres tipos: hiperplasia fibromuscular, diafragma membranoso y remanentes traqueobronquiales. CASO CLINICO: Se presenta un caso clínico de un paciente masculino de 39 meses con diagnóstico de estenosis congénita del esófago secundario a remanentes traqueobronquiales, que presentó múltiples episodios de vómito y reflujo desde los 4 meses del nacimiento. Ingresó en el Servicio de Urgencias por presentar signos de dificultad respiratoria, realizándosele estudios iniciales de endoscopia de vías digestivas altas y esofagograma. Se practicó resección de estenosis y anastomosis esofágica toracoscópica. CONCLUSIONES: Los remanentes traqueobronquiales son la segunda causa de presentación de la estenosis esofágica congénita. El manejo de esta patología puede ser de dos formas, ya sea por medio de dilataciones o quirúrgico, y la elección de una u otra va a depender de su etiología.

Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

Effect of preoperative oral pravastatin reload in systemic inflammatory response and myocardial damage after coronary artery bypass grafting. A pilot double-blind placebo-controlled study.

AIM: Statins exert pleiotropic effects that result in cardioprotective and antiinflammatory properties. There is a lack of information about the effect of preoperative reloading statin administration in surgical coronary patients regarding myocardial protection, systemic inflammatory response (SIR) attenuation and nitric oxide (NO) metabolism. METHODS: Thirty consecutive dyslipidemic patients under chronic treatment with statins were randomized to orally receive pravastatin 80 mg (N.=10), 40 mg (N.=10) or placebo (N.=10) two hours before anesthetic induction for non-emergent on-pump coronary artery bypass grafting (CABG) procedures. Perioperative peripheral venous and intraoperative CS blood samples were collected for determination of drug-related adverse effects, NO metabolism and both myocardial damage and SIR biomarkers. RESULTS: Pravastatin reloading resulted in a significant and dose-related intense attenuation of SIR, but no differences in cardiac damage biomarker levels were demonstrated. NO release and inducible nitric oxide synthase expression was significantly reduced in both treatment groups. Highest pravastatin doses significantly increased systemic creatine phosphokinase (CPK) concentration compared with intermediate doses but no other adverse effects were observed. CONCLUSION: Oral pravastatin reloading before non-emergent CABG significantly attenuates postoperative SIR and systemic NO/iNOS concentrations with no effect in perioperative myocardial damage. Highest pravastatin doses increase CPK levels and must be avoided in susceptible patients.

Análisis de marcadores de superficie celular de utilidad en el diagnóstico de la sepsis neonatal: Reporte preliminar / Utility of the cellular surface markers in the diagnosis of neonatal sepsis: Preliminary report

La cuantificación de poblaciones leucocitarias en sangre periférica puede realizarse con ayuda del análisis por citometría de flujo. Los valores de poblaciones leucocitarias en neonatos son frecuentemente contrastados con sangre periférica de adultos. El presente reporte preliminar muestra el análisis de tres muestras de sangre de cordón umbilical de pacientes sanos y tres muestras de sangre periférica de neonatos con diagnóstico de sepsis tardía. Los resultados obtenidos muestran que CD69, CD71 y CD45RO pueden ser de utilidad para diferenciar estados de sepsis en neonatos. En un estudio futuro, la propuesta es realizar un análisis multiparamétrico por citometría de flujo que permita un análisis integral de la sepsis neonatal.

Quantification of leukocyte populations in peripheral blood can be performed using flow cytometry. The leukocyte populations are often contrasted between neonate and adult peripheral blood. This preliminary report shows the analysis of three samples of umbilical cord blood of healthy subjects and three peripheral blood samples of newborns diagnosed with late sepsis. Our results show that CD69, CD71 and CD45RO could be useful to differentiate states of sepsis in neonates. We propose a subsequent study to generate a multiparametric flow cytometry analysis that will allow a comprehensive analysis of neonatal sepsis.

Is morphokinetic analysis the answer?

Efforts aimed at improving pregnancy rates have focused on the search for additional markers of viability to supplement current criteria for embryo selection. Time-lapse technology represents a powerful tool in assisted reproduction for evaluating embryos dynamically. Whilst standard methods of embryo assessment are based on subjective morphology evaluation at discrete time points, thereby limiting the information produced for embryo selection, time-lapse recording introduces several additional morphokinetic parameters for embryo evaluation. This additional information can improve implantation rates and reproductive outcomes. This review surveys available knowledge on time-lapse imaging to provide an overview of the advantages and applications of this technology.

KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction.

Kisspeptins, the products of the KiSS-1 gene acting via G protein-coupled receptor 54 (GPR54), have recently emerged as pivotal signals in the hypothalamic network triggering the preovulatory surge of gonadotropins and, hence, ovulation. Additional actions of kisspeptins at other levels of the hypothalamic-pituitary-ovarian axis have been suggested but remain to date scarcely studied. We report herein the pattern of expression of KiSS-1 and GPR54 in the human and nonhuman primate ovary and evaluate changes in ovarian KiSS-1 expression in a rat model of ovulatory dysfunction. KiSS-1 and GPR54 mRNAs were detected in human ovarian tissue and cultured granulosa-lutein cells. In good agreement, kisspeptin immunoreactivity was observed in cyclic human and marmoset ovaries, with prominent signals in the theca layer of growing follicles, corpora lutea, interstitial gland, and ovarian surface epithelium. GPR54 immunoreactivity was also found in human theca and luteal cells. Administration of indomethacin to cyclic female rats disturbed ovulation and resulted in a dramatic drop in ovarian KiSS-1, but not GPR54, cyclooxygenase-2 (COX-2), or progesterone receptor, mRNA levels at the time of ovulation; an effect mimicked by the selective COX-2 inhibitor NS398 and rescued by coadministration of PGE(2). Likewise, the stimulatory effect of human choriogonadotropin on ovarian KiSS-1 expression was partially blunted by indomethacin. In contrast, KiSS-1 mRNA levels remained unaltered in another model of ovulatory failure, i.e., the RU486-treated rat. In summary, we document for the first time the expression of KiSS-1/kisspeptin and GPR54 in the human and nonhuman primate ovary. In addition, we provide evidence for the ability of inhibitors of COX-2, known to disturb follicular rupture and ovulation, to selectively alter the expression of KiSS-1 gene in rat ovary. Altogether, our results are suggestive of a conserved role of local KiSS-1 in the direct control of ovarian functions in mammals.

Effects of tepoxalin, a dual inhibitor of cyclooxygenase/5-lipoxygenase, on events associated with NSAID-induced gastrointestinal inflammation.

Prostaglandins and thromboxanes are products of arachidonic acid metabolism via the cyclooxygenase (CO) enzyme and are responsible for the pain and swelling common to sites of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production of these substances and are used in the treatment of inflammatory diseases such as arthritis. However, one of the major side-effects of NSAID therapy is gastric ulceration. It is possible that inhibition of prostaglandin production and a related increase in the formation of leukotrienes via the 5-lipoxygenase (5-LO) enzymatic pathway are responsible for attracting inflammatory cells, causing local sites of inflammation and producing ulceration. To determine the effects of 5-LO inhibition on this hypothesis, studies were performed in rats to evaluate the effects of tepoxalin, a dual CO/LO inhibitor on leukotriene B4 levels in gastric mucosa and neutrophil adhesion in mesenteric venules. In rats, chronic oral administration of an NSAID, indomethacin (2 mg/kg daily over 4 days), resulted in 40% mortality, accompanied by intestinal adhesions and perforations when evaluated 24 h after the fourth dose of drug. Additionally, neutrophil adhesion was increased in the mesenteric venules and cell infiltration was evident in the mesenteric interstitium. These gastrointestinal side-effects were inhibited in a separate group of rats administered tepoxalin (20 mg/kg, p.o) 30 min prior to each daily indomethacin treatment. Further studies were performed to determine tepoxalin's effects on early events associated with NSAID-induced gastrointestinal inflammation, including neutrophil adhesion, lipid peroxide generation and LTB4 production. Indomethacin (100 mg/kg, p.o.) produced elevated levels of LTB4 in rat gastric mucosa 90 min after administration. Additionally, neutrophil adhesion in mesenteric venules was increased at this dose and with the administration of another NSAID, naproxen. No generation of lipid peroxides was evident in the gastric mucosa at this timepoint. Tepoxalin (up to 400 mg/kg, p.o.) did not have an effects on gastric mucosal LTB4 generation and lipid peroxide levels. A decrease in neutrophil adhesion was observed at the highest dose. In another study, pretreatment with tepoxalin (ED50=7.5 mg/kg, p.o.) or the selective 5-LO inhibitor zileuton (100 mg/kg, p.o.) prevented the increases in gastric mucosal LTB4 levels and neutrophil adhesion induced by indomethacin (100 mg/kg, p.o.). These data suggest that LO inhibition may play a vital role in the prevention of NSAID-induced gastric inflammation, providing insight into the lack of ulcerogenicity with tepoxalin and new approaches to anti-inflammatory therapy which may prevent gastric side effects.

Cytokine-modulating activity of tepoxalin, a new potential antirheumatic.

Tepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation. It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit IL-2 induced signal transduction. The current study was conducted to evaluate the cytokine modulating activity of tepoxalin and the role of iron in these effects. In human peripheral blood mononuclear cells (PBMC) stimulated with OKT3/PMA, tepoxalin inhibited lymphocyte proliferation with an IC50 of 6 microM. Additionally, it inhibited the production of LTB4 (IC50 = 0.5 microM) and the cytokines IL-2, IL-6 and TNF alpha (IC50 = 10-12 microM). Cytotoxicity was not demonstrated at these concentrations. Add-back experiments with either cytokines (IL-2 or IL-6), LTB4 or conditioned media failed to restore the proliferative response in the presence of tepoxalin. However, the concurrent addition of iron (in the form of ferrous or ferric chloride and other iron salts) reversed the inhibition of proliferation caused by tepoxalin. Tepoxalin also inhibits the activation of NF kappa B, a transcription factor which acts on several cytokine genes. Tepoxalin's effect on NF kappa B is also reversed by the addition of iron salts. These data suggest that the action of tepoxalin to inhibit proliferation in PBMC may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of NF kappa B and subsequent inhibition of cytokine production.

Reticulocyte measurements as a bioassay for erythropoietin.

The possibility of using reticulocyte counts in peripheral blood to assay erythropoietic activity of recombinant human erythropoietin (r-HuEPO) was evaluated in normal mice. Mice were injected subcutaneously with r-HuEPO on days 0, 1 and 2 and bled on day 4 for reticulocyte count determinations, using an automated counting system with thiazole orange fluorescent staining and flow cytometric analysis. Reticulocyte counts increased in a dose-dependent fashion upon administration of r-HuEPO. The reticulocyte count was unaffected by asialylated EPO as well as other substances tested (interleukin-1, interleukin-3, dexamethasone, human chorionic gonadotropin). These data demonstrate the usefulness of employing reticulocyte counts as a rapid, specific and reproducible assay for in vivo erythropoietic activity of r-HuEPO.

Contribuiçäo ao estudo fitoquímico de Eubrachion ambiguum (Hook et Arn.) Engl., Loranthaceae / Contribuition to phytochemical study of Eubrachion ambiguum (Hook et Arn.) Engl., Loranthaceae

Eubrachion ambiguum (Hook et Arn.) Engl. é uma planta muito usada em medicina popular como analgésico e em pneumonia, a qual foi submetida a uma análise fitoquímica. Entre os grupos químicos investigados, foi detectada a presença de esteróides e/ou triterpenos, flavonóides, fenóis, taminos condensados, gomas e mucilagens, heterosídeos antocianicos, oses, fenóis com posiçäo orto e meta livres e ácidos orgânicos, entre outros