Intralesional steroids in refractory caustic esophageal stricture. / Corticosteroide intralesional en estenosis esofágicas cáusticas refractarias.

OBJECTIVE: To analyze the efficacy of intralesional steroid treatment in refractory caustic esophageal stricture. MATERIALS AND METHODS: An analytical, retrospective study of patients receiving intralesional steroid treatment with triamcinolone acetonide as a result of refractory caustic esophageal stricture was carried out. Demographic variables, stricture characteristics, number of dilations, steroid injections, and dilation score (no. of dilations/follow-up period in months) pre- and post-treatment were collected. Stricture characteristics (diameter and length) and dilation score pre- and post-treatment were compared using the T-Test or Wilcoxon test. RESULTS: N= 5. Median age: 5 years (17 months-7 years). Follow-up: 6.60 ± 2.70 years. Swallowed products included NaOH, KOH, and ClH. Zargar classification at follow-up initiation was IIb (n= 2), IIIa (n= 1), and two chronic strictures. 6.6 ± 9.23 esophageal dilations were carried out before steroid treatment initiation. The mean number of intralesional therapy sessions was 11.20 ± 6.14. Stricture length decreased by 3.60 ± 2.63 cm (t= 3.06; p= 0.019). No differences were found in terms of diameter increase: -1.60 ± 3.58 mm (t= -1.00; p= 0.187). The dilation score diminished from 1.47 ± 0.86 to 0.47 ± 0.18 dilations per month of follow-up (Z= -2.02; p= 0.043). CONCLUSIONS: Even though there is limited evidence available in the pediatric population, intralesional triamcinolone treatment is seemingly useful in the treatment of refractory caustic esophageal stricture, since it reduces length and dilation score.

OBJETIVO: Analizar la eficacia del tratamiento intralesional con corticosteroide en estenosis esofágicas cáusticas refractarias. MATERIAL Y METODOS: Estudio analítico y retrospectivo de pacientes tratados con corticosteroide intralesional (triamcinolona acetónido) por estenosis esofágicas cáusticas refractarias. Se recogieron variables demográficas, características de la estenosis, número de dilataciones, inyecciones de corticosteroide e índice de dilatación (nº dilataciones/periodo de seguimiento en meses) pre y post tratamiento. Se compararon las características de la estenosis (diámetro y longitud) e índice de dilatación pre y post tratamiento con T-Test o Test de Wilcoxon. RESULTADOS: N= 5. Edad mediana 5 años (17 meses-7años) y seguimiento de 6,60 ± 2,70 años. Los productos ingeridos fueron NaOH, KOH y ClH. La clasificación de Zargar al inicio del seguimiento fue IIb (n= 2), IIIa (n= 1) y dos estenosis crónicas. Se realizaron 6,6 ± 9,23 dilataciones esofágicas previas al tratamiento con corticosteroide. El número de sesiones de terapia intralesional promedio fue 11,20 ± 6,14. La longitud de la estenosis mostró una reducción de 3,60 ± 2,63 cm (t= 3,06 ; p= 0,019). No encontramos diferencias en el incremento del diámetro: ­1,60 ± 3,58 mm (t= ­1,00 ; p= 0,187). El índice de dilatación se redujo de 1,47 ± 0,86 a 0,47 ± 0,18 dilataciones por mes de seguimiento (Z= ­2,02 ; p= 0,043). CONCLUSIONES: Aunque la evidencia disponible en población pediátrica es limitada, la terapia con triamcinolona intralesional parece ser útil en el tratamiento de estenosis esofágicas cáusticas refractarias, al reducir su longitud y el índice de dilatación.

Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients. / Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico.

INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.

INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.

Basal cell carcinoma-a clinical indicator of immunosuppression.

Background: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are skin-derived carcinomas. The literature strongly connects SCC with acquired immunosuppression. Current data regarding BCC's association with immunosuppressive comorbidities are vague. The primary objective of this study was to establish the correlations between BCC and immunosuppressive comorbidities of patients. Materials and methods: We conducted a retrospective cohort study on 275 patients with a histopathological proven diagnosis of BCC from October 2019 to October 2023. Demographic data, BCC characteristics, and patients' comorbidities were analyzed. Comorbidities were classified as non-immunosuppressant and immunosuppressant (primary and secondary immunodeficiencies). Results: We recorded 292 BCCs from 275 patients (142 females, 133 males), with equally distributed skin phototypes. 66.44% of the BCCs were detected in patients with various comorbidities (p < 0.001), of which 81.44% had immunosuppressive comorbidities (p < 0.001). All the immunosuppressive comorbidities were secondary and included diabetes mellitus (47.55%), history of solid or hematogenous cancer in the last 5 years (26.57%), chronic kidney disease (8.39%), chronic infections (9.09%), and antirheumatic immunosuppressive therapies (8.39%) (p < 0.001). BCC patients with immunosuppressive comorbidities did not develop larger BCCs (p = 0.2577) or more aggressive subtypes (p = 0.4269) and BCC did not arise earlier in their life (p < 0.001). BCC on the nasal pyramid was frequent in cancer history patients (p = 0.008). The ulcerated form of BCC is more confined to patients with chronic kidney disease (p = 0.006). Multiple BCCs are more frequent in patients with secondary immunodeficiencies (p = 0.027). Conclusion: BCC represents a clinical indicator of secondary immunodeficiency. Further research should establish if cancer screening campaigns may be beneficial in BCC patients.

Appropriateness of behavioural scales in the monitoring of pain in the critically ill patient unable to self-report.

Appropriateness is a dimension of quality that evaluates the effective use of technologies, resources or interventions in specific situations or populations, assessing whether our interventions do more benefit than harm. The evidence regarding pain monitoring in the critically ill patient points to the periodic assessment of pain using appropriate tools, with the aim of improving pain management and more efficient use of analgesics in the intensive care unit. The first step would be to assess the patient's ability to communicate or self-report and, based on this, to select the most appropriate pain assessment tool. In patients who are unable to self-report, behavioural pain assessment tools are recommended. When we talk about the suitability of behavioural scales for pain monitoring in critically ill patients unable to self-report, we refer to their use with a clear clinical benefit, i.e. using the right tool for pain assessment to be effective, efficient and consistent with bioethical principles. To our knowledge, there are no published data on the suitability of pain assessment tools in unable to self-report critically ill patients, so, in the framework of continuous quality improvement in pain care, new research should incorporate this approach by integrating the best scientific evidence with current clinical practice.

Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.

Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism.

Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.

Selective Neuronal Knockout of STAT3 Function Inhibits Epilepsy Progression, Improves Cognition, and Restores Dysregulated Gene Networks in a Temporal Lobe Epilepsy Model.

OBJECTIVE: Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and hippocampal neural circuit remodeling that results in spontaneous seizures and cognitive dysfunction. Targeting these cascades may provide disease-modifying treatments for TLE patients. Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors have emerged as potential disease-modifying therapies; a more detailed understanding of JAK/STAT participation in epileptogenic responses is required, however, to increase the therapeutic efficacy and reduce adverse effects associated with global inhibition. METHODS: We developed a mouse line in which tamoxifen treatment conditionally abolishes STAT3 signaling from forebrain excitatory neurons (nSTAT3KO). Seizure frequency (continuous in vivo electroencephalography) and memory (contextual fear conditioning and motor learning) were analyzed in wild-type and nSTAT3KO mice after intrahippocampal kainate (IHKA) injection as a model of TLE. Hippocampal RNA was obtained 24 h after IHKA and subjected to deep sequencing. RESULTS: Selective STAT3 knock-out in excitatory neurons reduced seizure progression and hippocampal memory deficits without reducing the extent of cell death or mossy fiber sprouting induced by IHKA injection. Gene expression was rescued in major networks associated with response to brain injury, neuronal plasticity, and learning and memory. We also provide the first evidence that neuronal STAT3 may directly influence brain inflammation. INTERPRETATION: Inhibiting neuronal STAT3 signaling improved outcomes in an animal model of TLE, prevented progression of seizures and cognitive co-morbidities while rescuing pathogenic changes in gene expression of major networks associated with epileptogenesis. Specifically targeting neuronal STAT3 may be an effective disease-modifying strategy for TLE. ANN NEUROL 2023;94:106-122.

Role of the nonribosomal peptide synthetase siderophore enzyme (Rfs) of Mucor lusitanicus in controlling the growth of fungal phytopathogens.

Dimorphic species of Mucor, which are cosmopolitan fungi belonging to subphylum Mucoromycotina, are metabolically versatile. Some species of Mucor are sources of biotechnological products, such as biodiesel from Mucor circinelloides and expression of heterologous proteins from Mucor lusitanicus. Furthermore, Mucor lusitanicus has been described as a model for understanding mucormycosis infections. However, little is known regarding the relationship between Mucor lusitanicus and other soil inhabitants. In this study, we investigated the potential use of Mucor lusitanicus as a biocontrol agent against fungal phytopathogens, namely Fusarium oxysporum f. sp. lycopersici, Fusarium solani, and Alternaria solani, which destroy economically important crops. Results showed that aerobic cell-free supernatants of the culture broth (SS) from Mucor lusitanicus inhibited the growth of the fungal phytopathogens in culture, soil, and tomato fruits. The SS obtained from a strain of Mucor lusitanicus carrying the deletion of rfs gene, which encodes an enzyme involved in the synthesis of siderophore rhizoferrin, had a decreased inhibitory effect against the growth of the phytopathogens. Contrarily, this inhibitory effect was more evident with the SS from an rfs-overexpressing strain compared to the wild-type. This study provides a framework for the potential biotechnological use of the molecules secreted from Mucor lusitanicus in the biocontrol of fungal phytopathogens.

Platelet-Rich Plasma (PRP) in Dermatology: Cellular and Molecular Mechanisms of Action.

Platelet-rich plasma (PRP) therapy has gained attention in the scientific field due to its potential regenerative effects and great benefit-risk ratio. This review extensively explores the most studied mechanisms of this therapy according to the etiopathogenesis of skin diseases: cellular proliferation, matrix formation, regulation of inflammation, angiogenesis, collagen synthesis, and the remodeling of new tissue. Moreover, it draws on newly reported and lesser-known effects of PRP: its anti-apoptotic effects, immunological suppression, decrease in melanin synthesis, anti-microbial effects, overexpression of miR-155, antioxidant effects, and their involved pathways. This work aims to provide a complete update for understanding PRP's benefits and clinical relevance in wound healing, alopecia, pigmentary disorders, scars, rejuvenation, lichen sclerosus, and other inflammatory dermatoses, based on the current evidence. Furthermore, recent reports with novel indications for PRP therapy are highlighted, and new potential pathways correlated with the pathogenesis of skin diseases are explored.

Cytotoxicity of extracts and compounds isolated from Croton echioides in animal tumor cell (HTC).

The search for compounds with anticancer effects is of paramount importance today due to the high incidence of the disease. The Euphorbiaceae family is known for having compounds with therapeutic properties, one of its genera being Croton. It has several species, which contain compounds already known for their biological activities, presenting anti-inflammatory, antimicrobial and anticancer properties. Thus, the cytotoxicity/antiproliferative activity of semi-purified fractions and compounds isolated from Croton echioides in liver tumor cells of Rattus norvegicus (HTC) was evaluated by the MTT test. The semi-purified fractions showed cytotoxicity at concentrations above 200 µg/mL, at 24, 48 and 72 hours, reaching cell viability of 24.78% [400 µg/mL] at 24 hours, 12.79% [500 µg/mL] at 48 hours and 10.57% [300 µg/mL] at 72 hours. For the isolated compounds, lupeol had a cytotoxic effect in all concentrations (1, 5, 10, 15, 20, 40, 60, 80 and 100 µg/mL) and tested times (24, 48 and 72 hours), reaching minimum viability of 4.37% [100 µg/mL], within 72 hours. The clerodan diterpenes CEH-1 and CEH-4 also showed antiproliferative activity, with minimum viability of 36.19% [100 µg/mL] over 72 hours and 21.33% [100 µg/mL] over 48 hours, respectively. However, the clerodan diterpenes CEH-2 and CEH-3 did not shows a cytotoxic effect for HTC cells. Thus, there is a cytotoxic/antiproliferative potential of C. echioides against tumor cells, with targeted to mitochondrial enzymes, associated with cell proliferation, indicating that this species deserves prominence in the search for new molecules for the treatment of cancer.

Impacto de la salud oral en la calidad de vida en relación a la caries dental y los determinantes sociales en migrantes venezolanos Lima-2019 / Impact of Oral Health on Quality of Life in Relation to Dental Caries and Social Determinants in Venezuelan Migrants Lima-2019

Resumen Evaluar los resultados del impacto de la salud oral en la calidad de vida mediante el OHIP-14 en relación a la caries dental y los determinantes sociales en migrantes venezolanos. Se realizó un estudio transversal en una población de 350 migrantes venezolanos (30.1±7,4 años; 52% Varones). Donde para evaluar el impacto de la salud oral en la calidad de vida se utilizó el cuestionario Oral Health Impact Profile spanish versión Lima (OHIP-14sp Lima), contrastándose tanto con factores clínicos (índice CPOD) como sociodemográficos, para poder determinar la influencia de estos sobre el instrumento. Se determinó el impacto de la salud oral en la calidad de vida (OHIP-14), según el promedio de puntaje general y por dimensiones. Posteriormente, se realizó un examen clínico evaluando la presencia de lesiones de caries dental (Índice CPOD) y se recolectaron datos sociodemográficos por medio de una encuesta. El promedio del OHIP-14sp Lima generó un impacto negativo del 10.6% en la población migrante. Donde la dimensión de Malestar Psicológico fue la que demostró una mayor frecuencia de impacto negativo con un porcentaje de 38,3%. Los resultados del OHIP-14 sp Lima en el total de migrantes evaluados, fueron bajos en términos porcentuales, generando en su mayoría un promedio de un impacto positivo. Sin embargo, no se puede descartar que factores sociodemográficos como el sexo y niveles de escolaridad; fueron factores que sí generaron un impacto negativo, afectando significativamente los resultados observados en una o varias de las dimensiones evaluadas mediante el instrumento OHIP-14 en el presente estudio.

Abstract To evaluate the results of the impact of oral health on quality of life through the OHIP-14 in relation to dental caries and social determinants in Venezuelan migrants. A cross-sectional study was carried out in a population of 350 Venezuelan migrants (30.1±7.4 years; 52% Men). Where to evaluate the impact of oral health on quality of life, the Oral Health Impact Profile Spanish version Lima questionnaire (OHIP-14sp Lima) was used, contrasting with both clinical (DMFT index) and sociodemographic factors, in order to determine the influence of these on the instrument. The impact of oral health on quality of life (OHIP-14) was determined, according to the average general score and by dimensions. Subsequently, a clinical examination was carried out evaluating the presence of dental caries lesions (DMFT Index) and sociodemographic data were collected through a survey. The average of the OHIP-14sp Lima generated a negative impact of 10.6% on the migrant population. The dimension of "Psychological Discomfort" was the one that showed a higher frequency of negative impact with a percentage of 38.3%. The results of the OHIP-14 sp Lima in the total of evaluated migrants were low in percentage terms, generating mostly an average of a positive impact. However, it cannot be ruled out that sociodemographic factors such as sex and levels of education; they were factors that did generate a negative impact, significantly affecting the results observed in one or more of the dimensions evaluated using the OHIP-14 instrument in the present study.

Real Time Water-In-Oil Emulsion Size Measurement in Optofluidic Channels.

In this work, we investigated a platform for real-time emulsion droplet detection and size measurement in optofluidic platforms. An 8.2 µm core diameter input optical fiber and a multi-mode Gradient Refractive Index (GRIN) output fiber were integrated into an acrylic microfluidic channel platform consisting of three layers. Water-in-oil emulsions were investigated, since relevant applications have emerged in the recent past for these types of emulsions, such as drug encapsulation as well as droplet-based Polymerase Chain Reaction (PCR) amplification of DNA, among others. The main contribution of this work is in understanding the main physical phenomena (i.e., total internal reflection, refraction, and interference) behind the complex transmittance pattern obtained for these droplets. For this purpose, a frequency domain electromagnetic wave propagation modelling of the structure using the Finite Element Method (FEM) was used along with experimental measurements.

Secretion of the siderophore rhizoferrin is regulated by the cAMP-PKA pathway and is involved in the virulence of Mucor lusitanicus.

Mucormycosis is a fungal infection caused by Mucorales, with a high mortality rate. However, only a few virulence factors have been described in these organisms. This study showed that deletion of rfs, which encodes the enzyme for the biosynthesis of rhizoferrin, a siderophore, in Mucor lusitanicus, led to a lower virulence in diabetic mice and nematodes. Upregulation of rfs correlated with the increased toxicity of the cell-free supernatants of the culture broth (SS) obtained under growing conditions that favor oxidative metabolism, such as low glucose levels or the presence of H2O2 in the culture, suggesting that oxidative metabolism enhances virulence through rhizoferrin production. Meanwhile, growing M. lusitanicus in the presence of potassium cyanide, N-acetylcysteine, a higher concentration of glucose, or exogenous cAMP, or the deletion of the gene encoding the regulatory subunit of PKA (pkaR1), correlated with a decrease in the toxicity of SS, downregulation of rfs, and reduction in rhizoferrin production. These observations indicate the involvement of the cAMP-PKA pathway in the regulation of rhizoferrin production and virulence in M. lusitanicus. Moreover, rfs upregulation was observed upon macrophage interaction or during infection with spores in mice, suggesting a pivotal role of rfs in M. lusitanicus infection.

Pediatric living donor liver transplantation: results of laparoscopic vs. open graft removal. / Trasplante hepático pediátrico de donante vivo, resultados en función de extracción del injerto por laparotomía vs. laparoscopia.

INTRODUCTION: Laparoscopic graft removal for pediatric living donor liver transplantation (PLDLT) reduces morbidity and surgical aggressiveness for the donor. It is important to assess whether the approach used for removal purposes compromises implantation. The objective of this study was to analyze PLDLT progression in children according to whether the graft had been removed laparoscopically or through open surgery. MATERIAL AND METHODS: A retrospective, analytical cohort study of PLDLTs carried out in our institution from 2009 to 2020 was carried out. RESULTS: Transplantation was performed in 14 patients, with a median age of 34.5 (R: 6-187) months. In 6 donors (42%), graft removal was conducted laparoscopically. In 1 donor (7%), removal was initiated laparoscopically, but conversion was required. This patient was included within the open surgery group, which consisted of 8 (58%) donors. No differences were found in terms of operating times, ICU stay, hospital stay, complications during admission, or complications post-admission in the recipient. The surgical approach did not compromise the length of the vessels to be anastomosed in any graft, and it added no extra difficulty to implantation. No differences were found in terms of removal times or hospital stay for the donor. Only 1 donor from the laparoscopy group required re-intervention due to bleeding following port insertion. CONCLUSION: PLDLT patients had similar results regardless of the removal approach used, which did not compromise the structures of the graft to be anastomosed, or add any extra difficulty to implantation.

INTRODUCCION: La extracción laparoscópica del injerto para el trasplante hepático pediátrico de donante vivo (THPDV) es una herramienta que reduce la morbilidad y agresividad quirúrgica en el donante. Es importante estudiar si la vía de extracción compromete el implante. El objetivo del estudio es analizar la evolución del THPDV en el niño en función de si el injerto fue extraído por vía abierta o laparoscopia. MATERIAL Y METODOS: Estudio de cohortes retrospectivo y analítico de los THPDV realizados entre 2009 y 2020 en nuestro centro. RESULTADOS: Se trasplantaron 14 pacientes, con edad mediana de 34,5 (R: 6-187) meses. En 6 donantes (42%) se realizó la extracción del injerto vía laparoscópica. En un donante se inició la extracción por laparoscopia, pero fue necesaria la conversión (7%), esté se clasificó en el grupo de laparotomía, compuesta por 8 (58%) donantes. No se encontraron diferencias en el tiempo quirúrgico, en los días en la unidad de cuidados intensivos, en la estancia hospitalaria, en las complicaciones durante el ingreso ni en las complicaciones postingreso en el receptor. El abordaje quirúrgico no comprometió en ningún injerto la longitud de los vasos a anastomosar, sin suponer una dificultad en el implante. No se evidenciaron diferencias en el tiempo de extracción ni en los días de hospitalización del donante. Solo un donante del grupo de laparoscopia precisó reintervención por sangrado de la incisión de un trocar. CONCLUSION: Los pacientes con THPDV presentan resultados similares, independientemente de la vía de extracción del injerto. La vía de abordaje no comprometió las estructuras del injerto a anastomosar, ni dificultó el momento del implante.

Down-regulation of AMPA receptors and long-term potentiation during early epileptogenesis.

Epilepsy is a brain disorder characterized by the occurrence of recurrent spontaneous seizures. Behavioral disorders and altered cognition are frequent comorbidities affecting the quality of life of people with epilepsy. These impairments are undoubtedly multifactorial and the specific mechanisms underlying these comorbidities are largely unknown. Long-lasting alterations in synaptic strength due to changes in expression, phosphorylation, or function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) have been associated with alterations in neuronal synaptic plasticity. In particular, alterations in hippocampal long-term potentiation (LTP), a well-accepted model of learning and memory, have been associated with altered cognition in epilepsy. Here, we analyzed the effects of pilocarpine-induced status epilepticus (SE) on AMPARs to determine if alterations in AMPAR signaling might be one of the mechanisms contributing to altered cognition during epilepsy. We found alterations in the phosphorylation and plasma membrane expression of AMPARs. In addition, we detected altered expression of GRIP, a key scaffolding protein involved in the proper distribution of AMPARs at the neuronal cell surface. Interestingly, a functional analysis revealed that these molecular changes are linked to impaired LTP. Together, these observations suggest that seizure-induced alterations in the molecular machinery regulating AMPARs likely impact the neuron's ability to support synaptic plasticity that is required for learning and memory.

Transcript pattern analysis of Arf-family genes in the phytopathogen Fusarium oxysporum f. sp. lycopersici reveals the role of Arl3 in the virulence.

Fusarium oxysporum f. sp. lycopersici is an important plant pathogen that has been used to understand the virulence mechanisms that soil inhabiting fungi exhibit during the infection process. In F. oxysporum many of the virulence factors are secreted, and the secretion process requires the formation of vesicles. Arf family members, represented by Arf (ADP- Ribosylation Factor), Arl (Arf-like), and Sar (Secretion-associated and Ras-related) proteins, are involved in the vesicle creation process. In this study we identified the Arf family members in F. oxysporum f. sp. lycopersici, which includes seven putative proteins: Arf1, Arf3, Arl1 through Arl3, Arl8B, and Sar1. Quantification of the mRNA levels of each arf encoding gene revealed that the highest expression corresponds to arf1 in all tested conditions. The phylogenetic analysis revealed that no other Arf1 paralogue, such as Arf2 from yeast, is present in F. oxysporum f. sp. lycopersici. The essential function suggested of Arf1 in F. oxysporum f. sp. lycopersici was corroborated experimentally when, after several attempts, it was impossible to obtain a knockout mutant in arf1. Moreover, arl3 mRNA levels increased significantly when plant tissue was added as a sole carbon source, suggesting that the product of these genes could play pivotal roles during plant infection, the corresponding mutant ∆arl3 was less virulent compared to the wild-type strain. These results describe the role of arl3 as a critical regulator of the virulence in F. oxysporum f. sp. lycopersici and stablish a framework for the arf family members to be studied in deeper details in this phytopathogen.

Altered Protein Profiles During Epileptogenesis in the Pilocarpine Mouse Model of Temporal Lobe Epilepsy.

Epilepsy is characterized by recurrent, spontaneous seizures and is a major contributor to the global burden of neurological disease. Although epilepsy can result from a variety of brain insults, in many cases the cause is unknown and, in a significant proportion of cases, seizures cannot be controlled by available treatments. Understanding the molecular alterations that underlie or are triggered by epileptogenesis would help to identify therapeutics to prevent or control progression to epilepsy. To this end, the moderate throughput technique of Reverse Phase Protein Arrays (RPPA) was used to profile changes in protein expression in a pilocarpine mouse model of acquired epilepsy. Levels of 54 proteins, comprising phosphorylation-dependent and phosphorylation-independent components of major signaling pathways and cellular complexes, were measured in hippocampus, cortex and cerebellum of mice at six time points, spanning 15 min to 2 weeks after induction of status epilepticus. Results illustrate the time dependence of levels of the commonly studied MTOR pathway component, pS6, and show, for the first time, detailed responses during epileptogenesis of multiple components of the MTOR, MAPK, JAK/STAT and apoptosis pathways, NMDA receptors, and additional cellular complexes. Also noted are time- and brain region- specific changes in correlations among levels of functionally related proteins affecting both neurons and glia. While hippocampus and cortex are primary areas studied in pilocarpine-induced epilepsy, cerebellum also shows significant time-dependent molecular responses.

Mass spore production of Mucor circinelloides on rice.

Mucor circinelloides is a fungus that produces diverse spores throughout its life cycle. The sporangiospores, which are the most well-studied spores in this fungus, are asexual spores produced during aerial mycelial development. M. circinelloides has the potential to be used in diverse biotechnological applications. In this study, we propose rice (Oryza sativa) grains as an alternative substrate for inexpensive and large-scale sporangiospore production. The sporangiospores produced from rice and a yeast extract-peptone-glucose (YPG) medium exhibited similar protein and nucleic acid contents and phenotypes in terms of germination under different conditions and culture media, including similar virulence rates against the nematode Caenorhabditis elegans. Transgenic strains carrying self-replicative plasmids were sporulated on rice and showed plasmid stability similar to that of spores produced on the YPG medium. Approximately 20% of the spore population lost plasmids after the first passage on rice. These results reveal that rice is a suitable substrate for the mass production of sporangiospores in M. circinelloides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02853-1.

Production of hydrogen-rich gases in the recycling process of residual carbon fiber reinforced polymers by pyrolysis.

In this work, a novel method to valorize the polymeric matrix of residual carbon fiber reinforced polymers (CFRP) in the recycling process of carbon fibers by pyrolysis is presented. The experiments have been carried out with an expired epoxy-based pre-preg and in a lab-scale installation composed of two reactors. In the first one, pyrolysis and oxidation have been carried out, while in the second one, the gases and vapors resulting from the thermal decomposition of the polymeric resin have been thermally treated. The following operating parameters have been studied in the pyrolysis step: dwell time, the use of N2 (N2 flow, no N2 flow and not even to inert the reaction medium) and the solid bed material of the second reactor. In the oxidation step, temperature and time have been optimized by using the theory of experiments based on 2 k factorial design was used. It has been demonstrated that clean carbon fibers and a gaseous fraction with 75% by volume of H2 can be obtained. This is possible through a combined process of (1) CFRP thermal decomposition at 500 °C, (2) thermal treatment of gases and vapors at 900 °C in a solid bed tubular reactor filled with a waste refractory material and (3) oxidation of pyrolysis solid at 500 °C during 165 min in presence of 1.3 L air min-1.

Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy.

BACKGROUND: The real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on overall mortality remains uncertain as surveillance reports have attributed a limited number of deaths to novel coronavirus disease 2019 (COVID-19) during the outbreak. The aim of this study was to assess the excess mortality during the COVID-19 outbreak in highly impacted areas of northern Italy. METHODS: We analysed data on deaths that occurred in the first 4 months of 2020 provided by the health protection agencies (HPAs) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardised mortality ratio (SMR) and cumulative number of excess deaths through a Poisson generalised additive model of the observed counts in 2020, using 2019 data as a reference. RESULTS: We estimated that there were 5740 (95% credible set (CS) 5552-5936) excess deaths in the HPA of Bergamo and 3703 (95% CS 3535-3877) in Brescia, corresponding to a 2.55-fold (95% CS 2.50-2.61) and 1.93 (95% CS 1.89-1.98) increase in the number of deaths. The excess death wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly 2 weeks after the introduction of lockdown measures, with significantly higher estimates in Bergamo (9.4, 95% CI 9.1-9.7). CONCLUSION: Excess mortality was significantly higher than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on the health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower excess mortality in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.