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Context Cutaneous T-cell lymphomas (CTCLs) are rare non-Hodgkin lymphomas that present in skin and include mycosis fungoides (MF) and Sezary syndrome (SS) subsets. Leukemic involvement is an independent prognostic factor affecting overall and disease-specific survival and increasing the risk of disease progression (Agar 2010, Am Soc J Clin Oncol). CTCL has serious negative effects on patient quality of life (QoL). Therefore, treatment goals include reducing the burden of disease, delaying progression, and improving or preserving QoL. Objective This post hoc analysis of MAVORIC trial data sought to determine whether baseline blood tumor burden affected treatment effects on patient QoL. Design The Phase 3 MAVORIC trial (NCT01728805) compared vorinostat 400 mg daily PO to mogamulizumab 1.0 mg/kg weekly for the first 28-day cycle, then on days 1 and 15 of subsequent cycles. Patient-reported outcome (PRO) analysis of health-related QoL (HRQoL) was performed using the validated Skindex-29 and FACT-G (Functional Assessment of Cancer Therapy-General) instruments. Pruritus was assessed using ItchyQoL and Pruritus Likert scales. All PROs were administered at baseline; Skindex-29 and FACT-G were then administered at every other treatment visit (Cycle 1, 3, 5, …), and ItchyQoL and Pruritus Likert scales were administered every 4 weeks at each cycle. Results Overall, no statistically significant differences between mogamulizumab and vorinostat were seen for patients without blood involvement. Statistically significant differences were seen for patients with blood involvement, with mogamulizumab-treated patients seeing statistically significant improvement in Skindex-29 for treatment Cycles 3–11 in all domains (emotional, functional, symptoms) and in the functional domain of ItchyQoL at most time points. In mogamulizumab-treated patients with blood involvement, the Pruritus Likert Scale score showed a reduction in itch from Cycle 1 and a trend toward reducing levels of itch over 12 cycles. The FACT-G Total Score showed the greatest improvement from baseline for mogamulizumab-treated patients with blood involvement compared to those without blood involvement and all vorinostat-treated patients. Conclusions Mogamulizumab patients with blood involvement saw greater HRQoL improvement than those without blood involvement. Mogamulizumab offers QoL benefit, assessed across a number of PROs, especially to patients with blood involvement (B1 or B2). Supported by Kyowa Kirin, Inc.

Background: Despite the high volume of admissions to the Puerto Rico Trauma Hospital (PRTH), the highest level trauma facility on the Island and the Caribbean, there is no evidence of recent trends related to pediatric trauma. In this study, we aim to describe and compare the epidemiology of pediatric trauma population in Puerto Rico according to age groups. Methods: An IRB-approved cross-sectional study of 853 pediatric admissions to the PRTH from January 2015 through June 2019. Comparison between age groups (children/adolescent vs. youth) was done using trends of proportions, chi-square for trends, and Pearson’s chi-square. Multivariate analysis of factors associated with the youth population was also performed. Results: The majority of patients were male (n=644, 75.5%). When stratified by age groups, motor vehicle accidents (MVA) were the prevalent mechanism of injury for all age categories but for subjects 15, was higher in the age group 15-21 years old (40.8%). In trends analysis, the occurrence of trauma was considerably higher among young adults (>15-21 years). Conclusion: Pediatric and young adults patients were more likely to be male and suffer from a MVA. In addition, among factors associated with injuries among the youth population were penetrating injuries, major trauma, a longer length of stay, and ICU stay. Understanding the specific characteristics of the pediatric population we treat can help guide the treatment and help elucidate their needs in order to improve their outcomes.

Reseña de: J.L. Nancy, Banalidad de Heidegger, Madrid: Trotta, 2019, 93 pp.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and despite advances in cancer treatment, there are still cases of relapse and death secondary to resistance to chemotherapy or apoptosis. One of the mechanisms is the activation of the IKK/NF-κB signaling pathway that leads to the expression of genes that interfere with apoptosis. Pentoxifylline (PTX) can block phosphorylation of IκB, thus preventing the NF-κB activity, therefore the activation of anti-apoptotic genes. Procedure: Controlled versus placebo, randomized, double-blind clinical trial. Pediatric patients with ALL during induction therapy were assigned either to pentoxifylline or the placebo group. Bone marrow aspirates were performed on day-1, day-8, day-15, and day-22. We performed flow MRD, determination of apoptosis by annexin-V/propidium iodide test, and senescence by β-galactosidase activity. Results: PTX group had higher percentage of apoptotic cells on day-8 (41.3% vs 19.4%, p=0.029), and day-15 (35.0% vs 14.2%, p

The use of constant pain and night pain as clinical markers for predicting the presence of underlying pathology in painful adolescent idiopathic scoliosis (AIS) patients has been questioned. Pain intensity has been recognized as an important domain in pain assessment. The numerical rating scale (NRS) is one of the most commonly validated tools to assess pain intensity in children above 8 years of age. The aim of this study was to assess the NRS as a predictor of underlying pathologies found by MRI in painful AIS patients. A cross-sectional study comprising of all AIS patients with back pain lasting >4 weeks from April 2015 to April 2019 was performed. An MRI was performed on each AIS patient presenting with back pain after a nondiagnostic history, physical examination and spinal X-ray. The pain was graded using the NRS, ranging from 0 to 10. Patients were divided into three groups: NRS (1-3), NRS (4-6) and NRS (7-10). Variables, including gender, age, scoliosis magnitude and presence of underlying pathology, were compared between the groups. A total of 186 AIS patients were evaluated in the study, were 66/186 (35.5%) of them had underlying pathologies. The mean age of subjects was 14.7 years, 85% being female. An underlying pathology was identified in 4/11 (36.4%) with NRS (1-3), 28/82 (34.2%) with NRS (4-6) and 34/93 (36.6%) with NRS (7-10) (P = 0.94). The use of an NRS was not found to be an adequate predictor for identifying an underlying pathology via MRI in painful AIS patients.

We present a topological analysis of the third upper molars (M3) using the recently developed ICAMER nomenclatural system as a way to understand the dental morphological similarity in sigmodontine rodents, the most speciose subfamily of cricetids. The method is explored in Scapteromys aquaticus and Abrothrix olivacea, taxa belonging to two diverse tribes, Akodontini and Abrotrichini, respectively, which exhibit high similarity regarding several craniodental traits as well as external anatomy. Both species show morphologically similar M3 in adults characterized by cylindrification and the isolation of a large central fossette arising from the marginal fusion of the anterior and posterior lobes. The results indicate that, before the wear, these rodents have a strongly different topological pattern at the cuspal level, mostly involving production of the connection between the main cusps. The central fossette derives from the isolation of part of the metaflexus in Scapteromys, while in Abrothrix it originates from the hypoflexus. The topological analysis provides a new approach to sigmodontine systematics, including the ability to detect diagnostic characters of both tribes. More important, it constitutes a new step toward an integrative phylogeny of fossil and living cricetids.

La hernia diafragmática congénita es una de las patologías clínicamente más demandantes en la edad pediátrica. Con los avances de cuidado intensivo neonatal, al mejorar la sobrevida se ha cambiado el abordaje quirúrgico en algunos centros, incluyendo la reparación con cirugía mínimamente invasiva. Se presenta el primer caso de reparación toracoscópica de una hernia diafragmática congénita en Costa Rica.

In the past decades, the grasses of the Paspalum genus have emerged as a versatile model allowing evolutionary, genetic, molecular, and developmental studies on apomixis as well as successful breeding applications. The rise of such an archetypal system progressed through integrative phases, which were essential to draw conclusions based on solid standards. Here, we review the steps adopted in Paspalum to establish the current body of knowledge on apomixis and provide model breeding programs for other agronomically important apomictic crops. In particular, we discuss the need for previous detailed cytoembryological and cytogenetic germplasm characterization; the establishment of sexual and apomictic materials of identical ploidy level; the development of segregating populations useful for inheritance analysis, positional mapping, and epigenetic control studies; the development of omics data resources; the identification of key molecular pathways via comparative gene expression studies; the accurate molecular characterization of genomic loci governing apomixis; the in-depth functional analysis of selected candidate genes in apomictic and model species; the successful building of a sexual/apomictic combined breeding scheme.

Sobre la distinción y disponibilidad de los nuevos taxones propuestos por Agnolin et al. 2019. Recientemente, Agnolin et al. (2019) describieron 14 especies nuevas de mamíferos, incluyendo 12 roedores, un murciélago y un carnívoro, y una nueva subespecie de roedor. Además, estos autores propusieron varios otros actos nomenclatoriales: algunas formas nominales se eliminaron de las sinonimias y se hipotetizaron como especies distintas; se nombraron tres nuevos géneros, una subtribu y una tribu demamíferos. Revisamos todos los actos nomenclatoriales propuestos por Agnolin et al. (2019) y concluimos que las 14 nuevas especies y la nueva subespecie, así como las formas eliminadas de las sinonimias, deben tratarse como sinónimos de especies ya conocidas. Sugerimos lo mismo con respecto a los tres nuevos taxones supraespecí cos presentados por Agnolin et al. (2019), de los cuales dos no están disponibles ya que no cumplen con las disposiciones del Código Internacional de Nomenclatura Zoológica. Terminamos esta contribución criticando la forma en que Agnolin et al. (2019) realizaron su abordaje taxonómico. Recently, Agnolin et al. (2019) described 14 new species of mammals, including 12 rodents,one bat, and one carnivore, and one new subspecies of rodent. In addition, these authors proposed severalother nomenclatorial acts: some nominal forms were removed from synonymies and hypothesized as distinctspecies, at the time that three new genera, one subtribe, and one tribe of mammals were also named. Wereviewed the merits of all nomenclatorial acts proposed by Agnolin at al. (2019) and concluded that all 14new species and the new subspecies, as well as those forms removed from synonymies, should be treatedas synonyms of already known species. We suggest the same regarding the three new supraspecic taxapresented by Agnolin et al., two of which are not available as they fail to comply with the provisions of theInternational Code of Zoological Nomenclature. We end this contribution criticizing the way that mammaltaxonomy was approached by Agnolin et al. (2019). Fil: Teta, Pablo Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina Fil: D'elía, Guillermo. Universidad Austral de Chile; Chile Fil: Jayat, Jorge Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina Fil: Gonçalves, Pablo Rodrigues. Universidade Federal do Rio de Janeiro; Brasil Fil: Simoes Libardi, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; Argentina. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil Fil: Oliveira, João Alves de. Universidade Federal do Rio de Janeiro. Museu Nacional; Brasil Fil: Moratelli, Ricardo. Fundación Oswaldo Cruz; Brasil Fil: Reis Percequillo, Alexandre. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil Fil: Prado, Joyce Rodrigues do. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil Fil: Ortiz, Pablo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina Fil: Hurtado, Natali. Universidad Nacional de San Agustin; Perú Fil: Schiaffini, Mauro Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Laboratorio de Investigaciones en Evolución y Biodiversidad; Argentina Fil: Abreu Jr., Edson Fiedler de. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; Brasil Fil: Chiquito, Elisandra Almeida. Instituto Nacional da Mata Atlântica; Brasil Fil: Giménez, Analía Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Laboratorio de Investigaciones en Evolución y Biodiversidad; Argentina Fil: Torres, Julio. Instituto de Investigación Biológica del Paraguay; Paraguay

A set of five new aromatic poly(imide)s (PIs) incorporating pendant acyclic alkyl moieties were synthesized. The difference among them was the length and bulkiness of the pendant group, which comprises of linear alkyl chains from three to six carbon atoms, and a tert-butyl moiety. The effect of the side group length on the physical, thermal, mechanical, and gas transport properties was analyzed. All PIs exhibited low to moderate molecular weights (Mn ranged between 27.930&ndash, 58.970 Da, and Mw ranged between 41.760&ndash, 81.310 Da), good solubility in aprotic polar solvents, except for PI-t-4, which had a tert-butyl moiety and was soluble even in chloroform. This behaviour was probably due to the most significant bulkiness of the side group that increased the interchain distance, which was corroborated by the X-ray technique (PI-t-4 showed two d-spacing values: 5.1 and 14.3 Å). Pure gas permeabilities for several gases were reported (PI-3 (Barrer): He(52), H2(46), O2(5.4), N2(1.2), CH4(1.1), CO2(23), PI-t-4 (Barrer): He(139), H2(136), O2(16.7), N2(3.3), CH4(2.3), CO2(75), PI-5 (Barrer): He(44), H2(42), O2(5.9), N2(1.4), CH4(1.2), CO2(27), PI-6 (Barrer): He(45), H2(43), O2(6.7), N2(1.7), CH4(1.7), CO2(32)). Consistent higher volume in the side group was shown to yield the highest gas permeability. All poly(imide)s exhibited high thermal stability with 10% weight loss degradation temperature between 448&ndash, 468 &deg, C and glass transition temperature between 240&ndash, 270 &deg, C. The values associated to the tensile strength (45&ndash, 87 MPa), elongation at break (3.2&ndash, 11.98%), and tensile modulus (1.43&ndash, 2.19 GPa) were those expected for aromatic poly(imide)s.

Summary Cutaneous T‐cell lymphomas (CTCLs) have a chronic, relapsing course, and the most common subtypes are mycosis fungoides and Sézary syndrome. The disease causes visible skin alterations and can also cause alopecia, pruritus and pain, all of which can impact patients’ health‐related quality of life (HRQoL). The goal of treatment is to reduce symptoms and prevent disease progression. However, treatment recommendations are often based on low levels of evidence due to the lack of well‐designed randomised clinical trials and treatment guidelines, and approved drugs vary considerably across different countries and regions. Currently, available treatments rarely lead to durable remissions and eventually become less effective, meaning patients often require multiple therapy changes. Skin‐directed therapies (SDTs) are first‐line treatments for early‐stage CTCL, whereas systemic therapies may be needed for early‐stage disease that does not respond to SDT or for advanced‐stage disease. However, patients can experience significant side‐effects with these treatments or may be unable to tolerate them. Hence, there is an unmet need for effective therapies with good safety profiles for the treatment of early‐ and late‐stage CTCL. Here, we review current treatment guidelines, investigational and approved treatments, the impact of CTCL on patients’ HRQoL, and the treatment of pruritus.

Background and Aims Massive intravascular hemolysis is a common condition of several pathologies. It is associated with acute kidney injury (AKI) and progressive impairment of renal function. In this context, free hemoglobin (Hb) can exert harmful effects by accumulating in the kidney, where induces oxidative stress and it becomes cytotoxic. NADPH oxidase 4 (Nox4) is the principal source of reactive oxygen species (ROS) in the kidney. Nox4 is mostly expressed in proximal tubular cells with lower levels in glomerulus. The role of Nox4 in renal damage is not clear, with studies reporting beneficial or deleterious actions depending of the environmental conditions. For that reason we aimed to investigate the role of Nox4 in massive intravascular hemolysis-associated AKI. Method To study the role of Nox4 in AKI caused by massive intravascular hemolysis, we performed an experimental model of intravascular hemolysis by intraperitoneal injection of phenylhydrazine (200 mg/kg) in wild type (Nox4+/+) and Nox4 knockout mice (Nox4-/-). Mice were sacrificed 24 and 72 hours after intravascular hemolysis induction. We collected serum, urine and tissues sample. We analyzed renal function, oxidative stress, cell death and inflammation in these samples. In other experiments, wild type mice were treated with GKT137831 (10mg/kg/day), a potent Nox4 and Nox1 inhibitor, and mice were sacrificed 72h after induction of hemolysis. We also performed in vitro experiments in murine tubular epithelial cells (MCT) and murine podocytes cells to investigate the regulation of Nox4 in Hb-stimulated cells treated or not with GKT137831. Results Induction of intravascular hemolysis in Nox4+/+ mice increased creatinine and BUN levels and enhanced the expression of tubular injury markers, such as NGAL. These pathological effects were reduced in Nox4 knockout mice. Then, we analyzed oxidative stress in our experimental model thought determination of HO-1, ferritin, GSH and lipid peroxidation levels. All of these oxidative markers were reduced in Nox4-/- mice with intravascular hemolysis as compared with Nox4+/+ mice. We also observed that inflammatory markers such as IL-6, cell death and podocytes injury markers were reduced in Nox4-/- mice than in wild type mice, specially 72 hours after phenylhydrazine injection. In line with these results, GKT137831 administration ameliorated intravascular hemolysis-associated renal function impairment. Moreover, oxidative stress, tubular injury markers and podocyte injury were reduced in hemolytic mice treated with GKT137831. GKT137831 also reduced Hb- and heme-mediated oxidative stress in MCT and podocytes. Conclusion Our results show the important role of Nox4 in renal injury associated to massive intravascular hemolysis. Moreover, the inhibition of Nox4 may be a potential therapeutic target to prevent renal damage associated to Hb accumulation. These findings provide new insights into novel aspects of Hb-toxicity and may have important pathogenic and therapeutic implications for intravascular hemolysis related diseases

Background and Aims Rhabdomyolysis is characterized by the breakdown of the skeletal muscle and the subsequent myoglobin (Mb) release into the bloodstream. A common complication of this syndrome is acute renal injury (AKI). Once filtered by the kidney, Mb causes oxidative stress, inflammation and tubular cell death. There is no specific treatment for rhabdomyolysis-AKI, so it is crucial a better understanding of this syndrome to identify new therapeutic targets. Klotho is an anti-aging protein mostly expressed by the kidney. In addition to its functions in the regulation of mineral metabolism, Klotho protects from AKI-harmful effects. However, no previous studies analyzed the role of Klotho in rhabdomyolysis. Method We performed a pre-clinical model of rhabdomyolysis in C57BL/6J mice (male, 12 weeks old, n=30) by intramuscular injection of 10 ml/kg of 50% glycerol (≥99.5% m/v). Mice were sacrificed 3 and 6 hours or 1, 3, 7 and 30 days after glycerol administration. To evaluate to beneficial effect of Klotho in rhabdomyolysis, C57BL/6J mice were injected intraperitoneally with 0.1 mg/kg recombinant mouse Klotho (1819-KL, R&D Systems), or vehicle (PBS) 30 minutes before and 1, 3 and 5 days after glycerol injection. Blood, urine and renal samples were collected to analyze renal function, Klotho/FGF23 levels, oxidative stress, inflammation, fibrosis and cell death, all of them pathological processes affecting Klotho expression. In addition, we carried out studies in murine tubular cells (MCTs) to study the molecular mechanisms involved in Klotho regulation. Results Our results indicate that rhabdomyolysis induces an early decrease in Klotho renal mRNA and protein expression as well as Klotho serum levels. Klotho levels decreased in line with augmentation of creatinine concentration, kidney inflammation (CCL2 and IL-6 mRNA expression) and tubular injury marker NGAL. Moreover, patients with rhabdomyolysis-AKI also showed lower plasma Klotho levels and increased FGF23 plasma concentration than age-matched healthy individuals. Renal klotho protein expression remained reduced one month after rhabdomyolysis-induction, in line with long term renal fibrosis and pro-inflammatory macrophage accumulation (F4/80+ cells). Exogenous recombinant Klotho administration ameliorated renal function and reduced rhabdomyolysis-mediated tubular cell death oxidative stress (4-HNE staining) and tubular injury 24h after glycerol injection. In the same line, Klotho administration during AKI development reduced long term renal fibrosis and macrophage infiltration one month later. Antioxidant therapies with N-acetylcysteine (NAC) and sulforaphane, a potent Nuclear factor erythroid-2-related factor 2 (Nrf2) inducer, reduced Mb-mediated Klotho decrease in cultured tubular cells. Inhibition of TNF-α and IL-6 with infliximab and tocilizumab, respectively, also reverted Mb-mediated Klotho decrease. Inhibition of the inflammatory NFkB and p38 pathways also prevented Mb-mediated Klotho reduction. Conclusion Our findings are the first to demonstrate decreased renal and soluble Klotho levels not only in the early phases of rhabdomyolysis-induced AKI, but also when renal function was recovered, indicating that long-term consequences of AKI, such as inflammation and fibrosis, are also involved in Klotho downregulation. In addition, our results also indicate that Klotho administration may be a potential strategy to decrease rhabdomyolysis- long term negative effects.

BackgroundAlthough great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored.MethodsIn this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 was determined using confocal microscopy.ResultsNotably, we observed that the addition of sNKp30 to the cervical cancer cell lines decreased tumor cell proliferation and migration rate, but had no effect on apoptosis. We also found that B7-H6 is selectively maintained in tumor cell lines, and that efforts to sort and purify B7-H6 negative or positive cells were futile, as negative cells, when cultured, regained the expression of B7-H6 and B7-H6 positive cells, when sorted and cultivated, lost a percentage of B7-H6 expression.ConclusionsOur results suggest that B7-H6 has an important, as of yet undescribed, role in the biology of the cervical tumor cells themselves, suggesting that this protein might be a promising target for anti-tumor therapy in the future.

Objectives: The hazardous environmental conditions hurricanes create might increase injury incidence almost 7 times. Therefore, a cohort study was performed at the Puerto Rico Trauma Hospital to compare morbidity and mortality patterns of patients after Hurricane Maria with a control period. Methods: Admissions from September 20, 2017, through January 20, 2018, constituted the post-Maria period (473 patients); the corresponding months of the previous year comprised the pre-Maria period (439 patients). Comparisons were done using Pearson’s chi-square or Mann-Whitney U-tests, as appropriate. A logistic regression was performed to assess the association between mortality and the study period. Results: Postlandfall admissions among patients aged 40-64 y increased by 6.6%, while among subjects between ages 18 and 39 y dropped by 7.0% (P = 0.03). Falls, gunshots, and burns were the injury mechanisms that varied the most across the exposure period. The median Injury Severity Score (13 vs 12; P = 0.05) and the frequency of Glasgow Coma Scale scores ≤8 (17.1% vs 10.9%; P = 0.03) were higher among poststorm patients. Moreover, a 2-fold (odds ratio = 1.93; 95% CI: 1.07-3.47) increase in mortality was observed after Maria, when adjusting for covariates. Conclusions: Following a hurricane, trauma centers might expect an older population, with more severe injuries and a 2-fold increased mortality risk.

The immune response of teleosts (bonefish) is altered by diazinon (DZN), an organophosphate pesticide. It has been suggested that such alteration is due to the extraneuronal cholinergic system in fish leukocytes that renders these cells a target of pesticides. Diazoxon (DZO), the oxon metabolite of DZN, has been attributed immunotoxic effects. Still, to date there are no reports on the effects of DZO upon parameters involved in the signaling cascade of immune response cells. Therefore, this work evaluated the effect of DZO on key parameters of cell signaling (intracellular Ca2+ flux, ERK 1/2 phosphorylation), cell proliferation, and antiproliferative processes (apoptosis, senescence, mitochondrial membrane potential) in spleen mononuclear cells of Nile tilapia fish. The results obtained show that DZO does not affect cell proliferation but causes a lack of response to stimulation with PMA and ionomycin to release intracellular calcium. In addition, it inhibits ERK 1/2 phosphorylation and causes loss of mitochondrial membrane potential, apoptosis, and senescence. These results suggest that the lack of cell response to release intracytoplasmic Ca2+ inhibits ERK which disrupts the mitochondrial membrane potential, leading to cell apoptosis and senescence. These findings prove that DZO significantly affects key parameters involved in the survival of immune response cells.

Angiotensin II (ANG II) plays a key role in regulating blood pressure and inflammation. Prostaglandin E2 (PGE2) signals through four different G protein-coupled receptors, eliciting a variety of effects. We reported that activation of the EP3 receptor reduces cardiac contractility. More recently, we have shown that overexpression of the EP4 receptor is protective in a mouse myocardial infarction model. We hypothesize in this study that the relative abundance of EP3 and EP4 receptors is a major determinant of end-organ damage in the diseased heart. Thus EP3 is detrimental to cardiac function and promotes inflammation, whereas antagonism of the EP3 receptor is protective in an ANG II hypertension (HTN) model. To test our hypothesis, male 10- to 12-wk-old C57BL/6 mice were anesthetized with isoflurane and osmotic minipumps containing ANG II were implanted subcutaneously for 2 wk. We found that antagonism of the EP3 receptor using L798,106 significantly attenuated the increase in blood pressure with ANG II infusion. Moreover, antagonism of the EP3 receptor prevented a decline in cardiac function after ANG II treatment. We also found that 10- to 12-wk-old EP3-transgenic mice, which overexpress EP3 in the cardiomyocytes, have worsened cardiac function. In conclusion, activation or overexpression of EP3 exacerbates end-organ damage in ANG II HTN. In contrast, antagonism of the EP3 receptor is beneficial and reduces cardiac dysfunction, inflammation, and HTN. NEW & NOTEWORTHY This study is the first to show that systemic treatment with an EP3 receptor antagonist (L798,106) attenuates the angiotensin II-induced increase in blood pressure in mice. The results from this project could complement existing hypertension therapies by combining blockade of the EP3 receptor with antihypertensive drugs.

The taxonomic history of Euryoryzomys legatus has been complex and controversial, being either included in the synonymy of other oryzomyine species or considered as a valid species, as in the most recent review of the genus. Previous phylogenetic analyses segregated E. legatus from E. russatus, its putative senior synonym, but recovered it nested within E. nitidus. A general lack of authoritative evaluation of morphological attributes, details of the chromosome complement, or other data types has hampered the ability to choose among alternative taxonomic hypotheses, and thus reach a general consensus for the status of the taxon. Herein we revisit the status of E. legatus using an integrated approach that includes: (1) a morphological review, especially centered on specimens from northwestern Argentina not examined previously, (2) comparative cytogenetics, and (3) phylogenetic reconstruction, using mitochondrial genes. Euryoryzomys legatus is morphologically and phylogenetically distinct from all other species-level taxa in the genus, but its 2n=80, FN=86 karyotype is shared with E. emmonsae, E. nitidus, and E. russatus. Several morphological and morphometric characters distinguish E. legatus from other species of Euryoryzomys, and we provide an amended diagnosis for the species. Morphological characters useful in distinguishing E. legatus from E. nitidus, its sister taxon following molecular analyses, include: larger overall size, dorsal fur with a strong yellowish brown to orange brown tinge, flanks and cheeks with an orange lateral line, ventral color grayish-white with pure white hairs present only on the chin, presence of a thin blackish eye-ring, tail bicolored, presence of an alisphenoid strut and a well-developed temporal and lambdoid crests in the skull, and a labial cingulum on M3. Molecular phylogenetic analyses recovered E. legatus as a monophyletic group with high support nested within a paraphyletic E. nitidus; genetic distances segregated members of both species, except for an exemplar of E. nitidus. Our integrated analyses reinforce E. legatus as a full species, but highlight that E. macconnelli, E. emmonsae, and E. nitidus each may be a species complex and worthy of systematic attention. Finally, we also evaluated the chromosome evolution of the genus within a phylogenetic context.

Literature in law and political science has suggested a number of factors explaining choices on the implementation constitutional review. However, so far little is known about how such factors combine in order to lead to different models of review. With the aid of configurational research, this article sheds light on that question for all countries of the current EU-28. In this region, the Kelsenian model of specialized courts, the\ud system of review by the judicial branch, and the model of parliamentary sovereignty still nowadays coexist. This article shows that phenomena such as the type of legal family of the country, existence of authoritarian backgrounds or political fragmentation played a major role in choices of models of constitutional review. However, it was only when they combined that they were capable of leading to particular outcomes.

In pregnancy, maternal monocytes and macrophages acquire a specific phenotype that enables them to maintain immune tolerance and facilitate hormone–immune cell interactions, which are necessary for gestational progression. The aim of this study was to determine the effect of pregnancy hormone mixtures of the first and third trimesters on both resting and activated monocytes and macrophages. Pregnancy hormone levels (cortisol, estradiol, progesterone, and prolactin) were quantified at the first and third trimesters. The average of the levels obtained was used to prepare two mixtures of synthetic hormones: low and high. These mixtures were then used to stimulate THP-1 monocytes and macrophages, resting or activated with LPS. Cytokine production in the culture supernatants and surface marker expression (CD14, CD86, and CD163) were evaluated by ELISA and flow cytometry, respectively. We found that the hormones modulated the pro-inflammatory response of THP-1 cells, LPS-activated monocytes, and macrophages, inducing high levels of IL-10 and low levels of IL-8, IL-1-β, and IL-6. All hormone stimulation increased the CD163 receptor in both resting and LPS-activated monocytes and macrophages in a dose-independent manner, unlike CD14 and CD86. Pregnancy hormones promote the expression of the markers associated with the M2-like phenotype, modulating their pro-inflammatory response. This phenotype regulation by hormones could be a determinant in pregnancy.

Breast cancer is the most frequent cancer in women worldwide, and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo-sulfur compounds, especially alliin and allicin. Here, we evaluated the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple-negative breast cancer cells. MCF-7 (luminal A) and HCC-70 (triple-negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST-1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC-10 fluorometric assay kit. Apoptosis-related genes were evaluated by RT-PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (β-Galactosidase Staining), and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspase-3, caspase-8, and caspase-9 activation, upregulation of NOXA, P21, and BAK, as well as downregulation of BCL-XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence, and did not exhibit pro-apoptotic effects in breast cancer cells.

BACKGROUND Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE To identify prognostic factors for specific survival in patients with PCALCL. METHODS Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P

Exergy and environmental analyses have been developed to determine the performance of the electricity generation in the Dutch mix. A comparative assessment of diverse technological routes, including fossil and renewable energy resources consumption, is carried out in terms of the exergy costs and specific CO2 emissions. Hence, an exergoeconomy methodology is used to properly allocate the renewable and non-renewable exergy costs and specific CO2 emissions among the various products of the polygeneration energy systems. By using a suitable methodology, the distribution of irreversibility throughout the different steps of the energy conversion processes of the Dutch electricity mix is characterized in the light of the Second Law of Thermodynamics. The results may help to propose performance indicators that support the Dutch government and research institutions. To identify sustainable energy planning strategies and fairly comparing electricity generation and end-use processing stages with other types of energy resources, such as fuels used in transportation, residential and industrial sectors. In brief, the weighted average of the renewable and non-renewable unit exergy costs and the specific CO2 emissions of the electricity generated in each route of the Dutch mix is calculated and compared to another electricity mix with a higher share of renewable energy resources. The weighted average renewable and non-renewable unit exergy costs of the electricity generated in the Netherlands are calculated as cR = 0.8375 kJ/kJE/W and cNR = 1.7180 kJ/kJE/W, respectively (cR/cNR= 0.49). Furthermore, the specific CO2 emissions in the Dutch electricity generation achieve 373.21 gCO2/kWhE/W.

Background: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. Methods: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. Results: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (–27.96 versus –8.62); the difference, –18.9 (95% confidence interval –26.6, –11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0–12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus –2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was –35.54 versus –11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. Conclusions: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. Clinical trial registration: NCT01578499.

In the past decades, the grasses of the Paspalum genus have emerged as a versatile model allowing evolutionary, genetic, molecular, and developmental studies on apomixis as well as successful breeding applications. The rise of such an archetypal system progressed through integrative phases, which were essential to draw conclusions based on solid standards. Here, we review the steps adopted in Paspalum to establish the current body of knowledge on apomixis and provide model breeding programs for other agronomically important apomictic crops. In particular, we discuss the need for previous detailed cytoembryological and cytogenetic germplasm characterization; the establishment of sexual and apomictic materials of identical ploidy level; the development of segregating populations useful for inheritance analysis, positional mapping, and epigenetic control studies; the development of omics data resources; the identification of key molecular pathways via comparative gene expression studies; the accurate molecular characterization of genomic loci governing apomixis; the in-depth functional analysis of selected candidate genes in apomictic and model species; the successful building of a sexual/apomictic combined breeding scheme.

Background The use of Mohs micrographic surgery (MMS) for rare cutaneous tumors is poorly defined. We aim to describe the demographics, tumor presentation and topography, surgery characteristics and complications of MMS for rare cutaneous tumors in a national registry. Methods Prospective cohort study of patients treated with MMS in Spain between July 2013 and June 2018. The inclusion criteria were patients with cutaneous tumors with final diagnosis different from basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, or any kind of melanoma. Results Five thousand and ninety patients were recorded in the registry, from which only 73 tumors (1.4%) fulfilled the inclusion criteria: atypical fibroxanthoma (18), microcystic adnexal carcinoma (10), extramammary Paget's disease (7), Merkel cell carcinoma (5), dermatofibroma (4), trichilemmal carcinoma (4), desmoplastic trichoepithelioma (4), sebaceous carcinoma (3), leiomyosarcoma (2), porocarcinoma (2), angiosarcoma (2), trichoblastoma (1), superficial acral fibromyxoma (1), and others (10). No intra-surgery morbidity was registered. Postsurgery complications appeared in six patients (9%) and were considered mild. Median follow-up time was 0.9 years during which three Merkel cell carcinomas, one angiosarcoma, one microcystic adnexal carcinoma, and four others recurred (12.3%). Conclusion This national registry shows that rare cutaneous tumors represent a negligible part of the total MMS performed in our country with a low complication rate.

Introduction Recent studies have observed that patients with treatment-resistant schizophrenia as well as patients with schizophrenia who do not respond within a medication trial exhibit excess activity of the glutamate system. In this study we sought to replicate the within-trial glutamate abnormality and to investigate the potential for structural differences and treatment-induced changes to improve identification of medication responders and non-responders. Methods We enrolled 48 medication-naive patients in a 4-week trial of risperidone and classified them retrospectively into responders and non-responders using clinical criteria. Proton magnetic resonance spectroscopy and T1-weighted structural MRI were acquired pre- and post-treatment to quantify striatal glutamate levels and several measures of subcortical brain structure. Results Patients were classified as 29 responders and 19 non-responders. Striatal glutamate was higher in the non-responders than responders both pre- and post-treatment (F1,39 = 7.15, p = .01). Volumetric measures showed a significant group x time interaction (t = 5.163, Conclusions Combining anatomic measures with glutamate levels offers the potential to enhance classification of responders and non-responders to antipsychotic medications as well as to provide mechanistic understanding of the interplay between neuroanatomical and neurochemical changes induced by these medications. Ethical statement The study was approved by the Ethics and Scientific committees of the Instituto Nacional de Neurologia y Neurocirugia in Mexico City. All participants over 18 years fully understood and signed the informed consent; in case the patient was under 18 years, informed consent was obtained from both parents. Participants did not receive a stipend.

New fossil material ofAuliscomys formosusReig 1978 allows restudy of the oldest known South American representative of the subfamily Sigmodontinae. Description ofAuliscomys formosuswas based on a fragmentary dentary exhumed from the Monte Hermoso Formation of central Argentina. Previous studies allocatedA. formosusto the early Pliocene. A reevaluation of dental and cranial morphology, including for the first time the upper dentition, and the inclusion ofA. formosusin a phylogenetic analysis of the tribe Phyllotini indicate thatA. formosusrepresents a new genus,Kraglievichimys.Kraglievichimysshares a mosaic of characters with the livingAuliscomysOsgood, 1915 andLoxodontomysOsgood, 1947. The taxonomic reassignment ofA. formosusand the possibility that the Monte Hermoso Formation may be younger than early Pliocene in age provide a new understanding of cricetid diversification in South America. Estimates of sigmodontine ancestry by molecular approaches are biased toward older ages, whereas this new interpretation of the history ofK. formosussuggests that the South American history of sigmodontines spans less than 4 million years.UUID:http://zoobank.org/49dd8f60-56b1-4e8a-a044-6cea3a1bd52b

BackgroundMutations in Melanoma Antigen-encoding Gene D2 (MAGED2) promote tubular dysfunction, suggesting that MAGE proteins may play a role in kidney pathophysiology. We have characterized the expression and regulation of MAGE genes in normal kidneys and during kidney disease.MethodsThe expression of MAGE genes and their encoded proteins was explored by systems biology multi-omics (kidney transcriptomics and proteomics) in healthy adult murine kidneys and following induction of experimental acute kidney injury (AKI) by a folic acid overdose. Changes in kidney expression during nephrotoxic AKI were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry. Factors regulating gene expression were studied in cultured tubular cells.ResultsFive MAGE genes (MAGED1, MAGED2, MAGED3, MAGEH1, MAGEE1) were expressed at the mRNA level in healthy adult mouse kidneys, as assessed by RNA-Seq. Additionally, MAGED2 was significantly upregulated during experimental AKI as assessed by array transcriptomics. Kidney proteomics also identified MAGED2 as upregulated during AKI. The increased kidney expression of MAGED2 mRNA and protein was confirmed by qRT-PCR and western blot, respectively, in murine folic acid- and cisplatin-induced AKI. Immunohistochemistry located MAGED2 to tubular cells in experimental and human kidney injury. Tubular cell stressors [serum deprivation and the inflammatory cytokine tumour necrosis factor-like weak inducer of apoptosis (TWEAK)] upregulated MAGED2 in cultured tubular cells.ConclusionsMAGED2 is upregulated in tubular cells in experimental and human kidney injury and is increased by stressors in cultured tubular cells. This points to a role of MAGED2 in tubular cell injury during kidney disease that should be dissected by carefully designed functional approaches.

This work describes mainly the synthesis and characterization of new co-polyimides obtained from the polycondensation of the dianhydride 4,4’-(hexafluoroisopropylidene)diphthalic anhydride (6FDA), 4,4’-oxydianiline (ODA) and the new diamine 3,5-diamino-N-(pyridin-4-ylmethyl)benzamide (PyDA). It describes as the different compositions of ODA and PyDA present in the polymers, produce variation on thermal and mechanical properties, which are important characteristics for the development of future nanocomposites derived from these polymers. Both PyDA monomer and polymers were characterized using FT-IR and NMR (1H, 13C, 19F, dept 135°, COSY, HMBC, HMQC) spectroscopy. The inherent viscosity of polymers is between 0.3 to 1.49 dL/g, they are soluble in aprotic polar solvents, such as: DMSO, DMF and DMA. In addition, all co-polymers showed thermal decomposition temperature and glass transition temperatures above 483 °C and 289 °C, respectively. Mechanical tests under tension of co-polymer films showed Young’s modulus between 2.1-3.9 GPa and tensile strength between 35.5 and 120.0 MPa. On the other hand, an increase in crystallinity and hydrophilicity is observed when increasing the amount of pyridinyl groups.

Purpose DM and trauma are leading causes of death in Hispanic patients, yet the interaction between them remains obscure. We aimed to assess the complications and in-hospital mortality rate of Hispanic diabetic trauma patients. Methods A retrospective cohort study was carried out using data from the Puerto Rico Trauma Hospital databank. Patients were matched based on gender, age, mechanism of injury, Glasgow Coma Scale, and Injury Severity Score using propensity-score matching. From 2000 to 2014, a total of 1134 patients with DM were compared to 1134 patients who did not have DM. The outcomes measured were hospital and TICU lengths of stay, days on mechanical ventilation, complications, and in-hospital mortality rate. A logistic regression model was carried out to evaluate the relationship of DM with complications and mortality after trauma. Results Hispanic patients with DM had longer hospital and TICU stays and required mechanical ventilation for extended periods. Complications, predominantly of an infectious nature, were more common among DM patients than they were among non-DM patients: 31.3% in the DM group vs. 11.6% in the non-DM group (OR 3.46; 95% CI 2.77–4.31). Despite an increase in the number of complications, DM was not associated with higher in-hospital mortality rates. Conclusions DM is associated with a twofold increase in complications in Hispanic diabetic trauma patients, which may account for their longer hospital and TICU stays. This indicates that diabetic Hispanic trauma patients may need earlier and more aggressive intervention to reduce their risk of developing complications.

Higher temperatures and reduced rainfalls that are expected with the advance of climate change can impair the emergence and establishment of tree seedlings in forest ecosystems. These climatic changes can also decrease the availability of soil resources and reduce the performance of seedlings. We evaluated these effects in a temperate forest from Mexico with two native oak species (Quercus crassifolia and Quercus eduardii). As recently emerged oak seedlings are highly sensitive to changing environmental conditions, our field experiment was conducted across the season in which seedling emergence occurs (October–February). In the field, we used open-top chambers to increase temperature and rainout shelters to reduce rainfall, while controls were exposed to the current climate. Experimental plots of both treatments were established beneath the forest canopy because most oaks recruit in understory habitats. In these plots, we sowed acorns of both species in October 2015 and recorded seedling emergence and survival until February 2016, also monitoring temperature, precipitation and contents of water and nitrogen in the soil. On seedlings that survived until the end of the experiment we measured their growth, photosynthetic efficiency and foliar contents of water, carbon and nitrogen. Both the emergence and survival of Q. crassifolia seedlings were lower in climate change plots than in controls, but no differences were found for Q. eduardii. However, seedlings of both species had lower growth rates, photosynthetic efficiencies and contents of water, nitrogen and carbon in climate change simulation plots. These results indicate that climate change can impair tree seedling establishment in oak forest, also suggesting that their development will be constrained by reduced water and nitrogen availability.

cAMP is a universal second messenger regulating a plethora of processes in the kidney. Two downstream effectors of cAMP are PKA and exchange protein directly activated by cAMP (Epac), which, unlike PKA, is often linked to elevation of [Ca(2+)](i). While both Epac isoforms (Epac1 and Epac2) are expressed along the nephron, their relevance in the kidney remains obscure. We combined ratiometric calcium imaging with quantitative immunoblotting, immunofluorescent confocal microscopy, and balance studies in mice lacking Epac1 or Epac2 to determine the role of Epac in renal water-solute handling. Epac1(−/−) and Epac2(−/−) mice developed polyuria despite elevated arginine vasopressin levels. We did not detect major deficiencies in arginine vasopressin [Ca(2+)](i) signaling in split-opened collecting ducts or decreases in aquaporin water channel type 2 levels. Instead, sodium–hydrogen exchanger type 3 levels in the proximal tubule were dramatically reduced in Epac1(−/−) and Epac2(−/−) mice. Water deprivation revealed persisting polyuria, impaired urinary concentration ability, and augmented urinary excretion of Na(+) and urea in both mutant mice. In summary, we report a nonredundant contribution of Epac isoforms to renal function. Deletion of Epac1 and Epac2 decreases sodium–hydrogen exchanger type 3 expression in the proximal tubule, leading to polyuria and osmotic diuresis.—Cherezova, A., Tomilin, V., Buncha, V., Zaika, O., Ortiz, P. A., Mei, F., Cheng, X., Mamenko, M., Pochynyuk, O. Urinary concentrating defect in mice lacking Epac1 or Epac2.

Introducción La hipertrofia amigdalina es una de las principales causas de ronquido infantil, teniendo una prevalencia que oscila entre el 9 y 10% alcanzando hasta el 30 % en niños entre los 3 – 6 años. Se debe nombrar que solo el 3% de ese 30% tienen OSA pues esa es la verdadera indicación de la cirugia El objetivo fue evaluar la seguridad y eficacia de la vaporización de amígdalas con láser CO2 en pacientes pediátricos con OSA del servicio de Otorrinolaringología en la Clínica Carlos Ardila Lülle-Bucaramanga.Métodos. Estudio descriptivo de 47 niños entre 3 y 11 años, sometidos al procedimiento entre enero del 2011 y febrero del 2012 por obstrucción ventilatoria alta con pausas respiratorias mayores de 10 segundos durante el sueño secundaria a hipertrofia del tejido amigdalino.Resultados. 97.8% de los niños estudiados tenían amígdalas grado IV y 2.1% grado III. Se debe exponer por que existe tan alto porcentaje en el grado IV la diferencia es muy grande y eso puede ser objeto de censura El tiempo quirúrgico fue en promedio de 25 minutos. En el 100% el procedimiento fue ambulatorio Hay que tener cuidado con esto por que los niños que van a cirugía por OSA como indicación, tienen que tener hospitalización posterior en UCI pues corren riesgo de tener apneas, puesto que sus receptores de CO2 disminuyen la sensibilidad de hipoxia pues al quitar el tejido no hay obstrucción y sus niveles de CO2 bajan mucho y esto es lo único que estimula en los centros respiratorios de ellos y al disminuir esto, se da la apnea. 24 niños no registraron dolor (51%), 2 pacientes presentaron emesis (0.94%). La evolución post intervención fue satisfactoria en la mayoría y ninguno de los pacientes presentó cuadros de sangrado o infección. Al mes posterior al procedimiento, 98% de los padres referían una notable mejoría de la respiración oral, ronquido, sueño y síntomas diurnos Episodios de apnea por que sino seria una cirugía sin criterios adecuados según lo que dice la literatura. En aquellos pacientes que cumplían 1 año de evolución no se evidenció en ninguno hipertrofia del tejido residual

The chemokine CCL20 activates the CCR6 receptor and has been implicated in the pathogenesis of glomerular injury. However, it is unknown whether it contributes to acute kidney injury (AKI). We identified CCL20 as upregulated in a systems biology strategy combining transcriptomics of kidney tissue from experimental toxic folic acid-induced AKI and from stressed cultured tubular cells and have explored the expression and function of CCL20 in experimental and clinical AKI. CCL20 upregulation was confirmed in three models of kidney injury induced by a folic acid overdose, cisplatin or unilateral ureteral obstruction. In injured kidneys, CCL20 was expressed by tubular, endothelial, and interstitial cells, and was also upregulated in human kidneys with AKI. Urinary CCL20 was increased in human AKI and was associated with severity. The function of CCL20 in nephrotoxic folic acid-induced AKI was assessed by using neutralising anti-CCL20 antibodies or CCR6-deficient mice. CCL20/CCR6 targeting increased the severity of kidney failure and mortality. This was associated with more severe histological injury, nephrocalcinosis, capillary rarefaction, and fibrosis, as well as higher expression of tubular injury-associated genes. Surprisingly, mice with CCL20 blockade had a lower tubular proliferative response and a higher number of cells in the G2/M phase, suggesting impaired repair mechanisms. This may be related to a lower influx of Tregs, despite a milder inflammatory response in terms of chemokine expression and infiltration by IL-17+ cells and neutrophils. In conclusion, CCL20 has a nephroprotective role during AKI, both by decreasing tissue injury and by facilitating repair. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

We assessed inter-seasonal dynamics of seed banks, dormancy and seed germination in three endemic Chihuahuan Desert succulent species, under simulated soil warming conditions. Hexagonal open top-chambers (OTCs) were used to increase soil temperature. Seeds ofEchinocactus platyacanthus(Cactaceae),Yucca filiferaandAgave striata(Asparagaceae) were collected and buried within and outside OTCs. During the course of one year, at the end of each season, seed batches were exhumed to test viability and germination. Soil temperature in OTCs was higher than in control plots.Yucca filiferaseeds always had high germination independently of warming treatment and season.Agave striataseeds from OTCs had higher germination than those from control plots.Agave striataexhibited low germination in fresh seeds, but high germination in spring. Seeds from this species lost viability throughout the experimental timeframe, and had no viable seeds remaining in the soil.Echinocactus platyacanthusshowed high germination in fresh seeds and displayed dormancy cycling, leading to high germination in spring, low germination in summer and autumn, and high germination in winter. Germination of this species was also higher in seeds from OTCs than those from control plots.Echinocactus platyacanthusformed soil seed banks and its cycle of inter-seasonal dormancy/germination could be an efficient physiological mechanism in a climate change scenario. Under global warming projections, our results suggest that future temperatures may still fall within the three studied species’ thermal germination range. However, higher germination forA. striataandE. platyacanthusat warmer temperatures may reduce the number of seeds retained in the seed bank, and this could be interpreted as limiting their ability to spread risk over time. This is the first experimental study projecting an increase in soil temperature to assess population traits of succulent plants under a climate change scenario for American deserts.

IntroducciónLa infección posquirúrgica en la columna lumbar es desafortunadamente común, multifactorial y una complicación potencialmente devastadora, que se asocia a un incremento de la morbilidad y la necesidad de futuras cirugías, y en última instancia, puede ser mortal. Con la intención de disminuir la morbilidad posquirúrgica, la medicación y los días de internación, comenzamos a utilizar aloinjerto fresco congelado de cabeza femoral de donantes vivos, en la artrodesis lumbar corta. El objetivo de este estudio fue comparar el índice de infección en la artrodesis lumbar corta en pacientes con aloinjerto fresco congelado y con autoinjerto.Materiales y MétodosEstudio retrospectivo de 153 pacientes divididos en dos grupos: grupo A: 84 pacientes con autoinjerto de cresta ilíaca y grupo B: 69 pacientes con aloinjerto fresco congelado, desde marzo de 2009 hasta enero 2014, sometidos cirugía instrumentada de fusión espinal lumbar posterolateral.ResultadosTres de los 153 pacientes operados se perdieron en el seguimiento (2 del grupo A y 1 del grupo B) y la muestra incluyó 150 pacientes (82 del grupo A y 68 del grupo B). Se produjeron tres infecciones por Staphylococcus aureus sensible a la meticilina, todas en el grupo A (4,5%). Ningún paciente de los dos grupos necesitó transfusión.ConclusionesEl uso de aloinjerto fresco congelado en las cirugías de columna lumbar posterolateral de causa degenerativa no se asocia a un aumento en la tasa de infección. Consideramos que el aloinjerto fresco congelado es una excelente alternativa, porque disminuye el tiempo quirúrgico y de hospitalización.

Pentoxifylline is a xanthine that possesses antitumor properties and that can induce higher apoptosis in the leukemic cells of pediatric patients with acute lymphoblastic leukemia (ALL) during treatment with prednisone. We conducted a phase 1 pilot, controlled, randomized trial to evaluate the gene expression modified by pentoxifylline during the steroid window of induction to remission phase in patients newly diagnosed with ALL. Experimental and control treatments induced broad changes in the gene expression profile. Patients who received just prednisone upregulated 377 and downregulated 344 genes, in contrast with patients treated with the experimental treatment (combination of prednisone and pentoxifylline), who demonstrated upregulation of 1319 and downregulation of 1594 genes. The most important genes modified in this pathway are those with proapoptotic activity, the majority of these overexpressed. Thus, the addition of pentoxifylline to the treatment with prednisone during steroid window in patients with ALL modified the gene expression profile and changed different signal pathways of the leukemic cell. The combination of both drugs represents a therapeutic alternative for potentiating antileukemic therapy.

Resumen La reciente publicacion de los resultados de ensayos clinicos en los que la diseccion ganglionar no ha demostrado beneficio de supervivencia en pacientes con metastasis en el ganglio centinela plantea la necesidad de modificar el tratamiento del paciente con melanoma. El presente trabajo aporta una actualizacion de la evidencia sobre diferentes aspectos necesarios (vias de progresion metastasica, factores predictores, tratamiento adyuvante, etc.) para la toma de decisiones en el paciente con melanoma y metastasis en el ganglio centinela y plantea un algoritmo de toma de decisiones para este escenario clinico. La evidencia actualmente disponible respalda el abandono de la diseccion ganglionar en aquellos pacientes con metastasis de bajo riesgo en el ganglio centinela (carga tumoral en el ganglio centinela inferior o igual a 1 mm).

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with low-risk sentinel node metastasis (sentinel node tumor load ≤ 1 mm).

Since 2012, the general opinion in Chile is that the Legislative has established in Article 17 No. 8 of the Law No. 20,600 a new general action to review any environmental agency action. This paper contends this idea, claiming that Law No. 20,600 only vested environmental courts with jurisdiction involving that type of actions, but this action has not yet been established. Therefore, potential claimants only could bring it only when the Legislative Branch regulates all its procedural aspects. Actually, the hesitant Supreme Court’s decisions in the last few months is a clear proof of that statement.