Malaria diagnosis using a combined system of a simple and fast extraction method with a lyophilised Dual-LAMP assay in a non-endemic setting.

Malaria is a parasitic disease distributed in tropical areas but with a high number of imported cases in non-endemic countries. The most specific and sensitive malaria diagnostic methods are PCR and LAMP. However, both require specific equipment, extraction procedures and a cold chain. This study aims to solve some limitations of LAMP method with the optimization and validation of six LAMP assays, genus and species-specific, using an easy and fast extraction method, the incorporation of a reaction control assay, two ways (Dual) of result reading and reagent lyophilization. The Dual-LAMP assays were validated against the Nested-Multiplex Malaria PCR. A conventional column and saline extraction methods, and the use of lyophilized reaction tubes were also assessed. A new reaction control Dual-LAMP-RC assay was designed. Dual-LAMP-Pspp assay showed no cross-reactivity with other parasites, repeatability and reproducibility of 100%, a significant correlation between parasite concentration and time to amplification and a LoD of 1.22 parasites/µl and 5.82 parasites/µl using column and saline extraction methods, respectively. Sensitivity and specificity of the six Dual-LAMP assays reach values of 100% or close to this, being lower for the Dual-LAMP-Pm. The Dual-LAMP-RC assay worked as expected. Lyophilized Dual-LAMP results were concordant with the reference method. Dual-LAMP malaria assays with the addition of a new reaction control LAMP assay and the use of a fast and easy saline extraction method, provided low limit of detection, no cross-reactivity, and good sensitivity and specificity. Furthermore, the reagent lyophilization and the dual result reading allow their use in most settings.

Factors associated with different patterns of weight change after bariatric surgery: A longitudinal study.

Background: The mean weight loss (WL) after successful bariatric surgery is approximately one third of the initial body weight, which is mainly achieved between the first 2 years of follow-up. However, 15%-35% of patients do not achieve a significant percentage of total WL (%TWL). Information on factors associated with a higher or lower WL after bariatric surgery is limited. This study aimed to assess the change in %TWL and describe the factors associated with greater or lesser WL over time. Methods: This prospective longitudinal study included patients treated with laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy. Baseline data were recorded before surgery. Follow-up was performed at 3 (n = 141), 6 (n = 208), 9 (n = 115), 12 (n = 216), 24 (n = 166), and 36 months (n = 99). Generalized estimating equation analysis was performed to assess the changes in %TWL over time and factors associated with different patterns of WL. Results: In total, 231 patients were included (women, 82.2%; basal body mass index (BMI) 41.4 ± 5.1 kg/m2). The tendencies to increase %TWL (32 ± 6.5) were evident in the first year and stabilized thereafter. Sustained nutritionist follow-up (2.3%, p = 0.004), baseline BMI >40 kg/m2 (0.4%, p < 0.001), and WL ≥ 10 kg before surgery (0.3%, p = 0.001) were associated with a higher %TWL. Patients who performed physical activity >30 min/day after surgery reduced their %TWL by 0.6% (p = 0.002). Conclusions: Modifiable factors such as nutritional monitoring and WL before surgery are associated with a significant increase in %TWL over time. Basal BMI was associated with a significant decrease in %TWL.

Validation and Application of UPLC-MS/MS Method to Analysis of Glyphosate and its Metabolites in Water.

A method was developed to determine glyphosate and their metabolites in water. The widespread use of this herbicide in agricultural activities worldwide, despite the reported adverse effects on both the environment and health, is a cause for concern and makes it necessary to monitor its presence through a method that guarantees the determination at trace levels. A direct extraction of the analytes with phosphate buffer was performed with subsequent derivatization with 9-fluorenylmethyl chloroformate. The quantification was determined by Ultra Performance Liquid Chromatography-tandem mass spectrometer. The method was validated through the following parameters: selectivity, detection and quantification limits, linearity, accuracy, precision and uncertainty. The average recoveries ranged between 94.08 and 103.31%. Additionally, detection limits from 0.396 to 0.433 µg/L, and the quantification limit was 5.0 µg/L for all the analytes evaluated. In terms of linearity and precision, the results obtained were in the ranges considered adequate (R2 ≥ 0.99 and CV ≤ 20%), the estimated expanded uncertainty was 12.95, 11.15 and 13.83% for glyphosate, aminomethylphosphonic acid and glufosinate, respectively. This method was successfully applied for the determination of the target analytes in irrigation water samples, detecting concentrations of aminomethylphosphonic acid over limit detection for some sampling sites.

Physiological responses to hypoxia are constrained by environmental temperature in heterothermic tenrecs.

Malagasy tenrecs are placental hibernating mammals that seal the entrances to their burrows and hibernate either singly or in groups for 8-9 months, which is likely to create a hypoxic and hypercapnic burrow environment. Therefore, we hypothesized that tenrecs are tolerant to environmental hypoxia and hypercapnia. Many hypoxia- and hypercapnia-tolerant fossorial mammals respond to hypoxia by decreasing metabolic rate and thermogenesis, and have blunted ventilatory responses to both environmental hypoxia and hypercapnia. However, tenrecs exhibit extreme metabolic and thermoregulatory plasticity, which exceeds that of most heterothermic mammals and approaches that of ectothermic reptiles. Thus, we predicted that tenrecs would have abnormal physiological responses to hypoxia and hypercapnia relative to other fossorial mammals. To test this, we exposed common tenrecs (Tenrec ecaudatus) to moderate and severe hypoxia (9 and 4% O2) or hypercapnia (5 and 10% CO2) in either 28 or 16°C while non-invasively measuring metabolic rate, thermogenesis and ventilation. We found that tenrecs exhibit robust metabolic decreases in both hypoxia and hypercapnia. Furthermore, tenrecs have blunted ventilatory responses to both hypoxia and hypercapnia, and these responses are highly temperature sensitive such that they are reduced or absent in 16°C. Thermoregulation was highly variable in 16°C but constrained in 28°C across all treatment conditions and was not impacted by hypoxia or hypercapnia, unlike in other heterothermic mammals. Taken together, our results indicate that physiological responses to hypoxia and hypercapnia in tenrecs are highly dependent on environmental temperature and differ from those of other mammalian heterotherms.

Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.

Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.

Circadian control of hepatitis B virus replication.

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown. We establish a circadian cycling liver cell-model and demonstrate that REV-ERB directly regulates NTCP-dependent hepatitis B and delta virus particle entry. Importantly, we show that pharmacological activation of REV-ERB inhibits HBV infection in vitro and in human liver chimeric mice. We uncover a role for BMAL1 to bind HBV genomes and increase viral promoter activity. Pharmacological inhibition of BMAL1 through REV-ERB ligands reduces pre-genomic RNA and de novo particle secretion. The presence of conserved E-box motifs among members of the Hepadnaviridae family highlight an evolutionarily conserved role for BMAL1 in regulating this family of small DNA viruses.

Síndrome metabólico: una revisión de criterios internacionales / Metabolic syndrome: A revision of international criteria

Resumen Introducción: El síndrome metabólico se conoce como el conjunto de condiciones médicas que incluyen obesidad de distribución central, aumento de los triglicéridos, dislipidemia aterogénica, hiperglucemia e hipertensión arterial. Objetivo: Comparar los principales criterios de diagnóstico usados en la actualidad para el diagnóstico del síndrome metabólico. Metodología: Se realizó una revisión bibliográfica retrospectiva mediante la consulta de bases de datos de los sistemas referativos, como SciELO, National Center for Biotechnology Information (NCBI) y ScienceDirect, con el uso de palabras clave validadas en DeCS y Mesh en inglés y español. Resultados: La obesidad abdominal es uno de los puntos más discrepantes en las diferentes organizaciones que describen el diagnóstico para síndrome metabólico. Conclusiones: Los criterios más estudiados para la población latinoamericana son los definidos por la Federación Internacional de Diabetes, a diferencia de los del Adult Treatment Panel III que tienen un punto de corte de perímetro abdominal más amplio, el cual dificulta el diagnóstico del síndrome metabólico.

Abstract Introduction: Metabolic syndrome is referred to as the set of medical conditions that include central distribution obesity, triglyceride elevation, atherogenic dyslipidemia, hyperglycemia and arterial hypertension. Objective: To compare the main diagnostic criteria currently used for the diagnosis of Metabolic Syndrome. Methodology: A retrospective bibliographic review was carried out by consulting databases of refectory systems, such as SciELO, National Center for Biotechnology Information (NCBI), ScienceDirect, with the use of validated keywords in DeCS and Mesh in both English and Spanish. Results: Abdominal obesity was found to be one of the most discrepant points in the different organizations that describe the diagnosis for metabolic syndrome. Conclusions: The most studied criteria for the Latin American population are those defined by the International Diabetes Federation, unlike those of the Adult Treatment Panel III that have a wider abdominal perimeter cut-off point, making it difficult to diagnose metabolic syndrome.

A PCR assay to quantify patterns of HBV transcription.

Hepatitis B virus (HBV) is the prototype member of the family Hepadnaviridae and replicates via episomal copies of a covalently closed circular DNA (cccDNA) genome of approximately 3.2 kb. The chromatinization of this small viral genome, with overlapping open reading frames and regulatory elements, suggests an important role for epigenetic pathways to regulate HBV transcription. However, the host pathways that regulate HBV transcription and the temporal nature of promoter usage in infected cells are not well understood, in part due to the compact genome structure and overlapping open reading frames. To address this we developed a simple and cost-effective PCR assay to quantify the major viral RNAs and validated this technique using current state-of-art de novo HBV infection model systems. Our PCR method is three orders of magnitude more sensitive than Northern blot and requires relatively small amounts of starting material, making this an attractive tool for assessing HBV transcription.

Hypoxic microenvironment shapes HIV-1 replication and latency.

Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1.

Glucose and glutamine availability regulate HepG2 transcriptional responses to low oxygen.

Background: Little is known about the impact of nutrients on cellular transcriptional responses, especially in face of environmental stressors such as oxygen deprivation. Hypoxia-inducible factors (HIF) coordinate the expression of genes essential for adaptation to oxygen-deprived environments. A second family of oxygen-sensing genes known as the alpha-ketoglutarate-dependent dioxygenases are also implicated in oxygen homeostasis and epigenetic regulation. The relationship between nutritional status and cellular response to hypoxia is understudied. In vitro cell culture systems frequently propagate cells in media that contains excess nutrients, and this may directly influence transcriptional response in hypoxia. Methods: We studied the effect of glucose and glutamine concentration on HepG2 hepatoma transcriptional response to low oxygen and expression of hypoxia inducible factor-1α (HIF-1α). Mass spectrometry confirmed low oxygen perturbation of dioxygenase transcripts resulted in changes in DNA methylation. Results: Under normoxic conditions, we observed a significant upregulation of both HIF-target genes and oxygen-dependent dioxygenases in HepG2 cells cultured with physiological levels of glucose or glutamine relative to regular DMEM media, demonstrating that excess glutamine/glucose can mask changes in gene expression. Under hypoxic conditions, CA9 was the most upregulated gene in physiological glutamine media while TETs and FTO dioxygenases were downregulated in physiological glucose. Hypoxic regulation of these transcripts did not associate with changes in HIF-1α protein expression. Downregulation of TETs suggests a potential for epigenetic modulation. Mass-spectrometry quantification of modified DNA bases confirmed our transcript data. Hypoxia resulted in decreased DNA hydroxymethylation, which correlated with TETs downregulation. Additionally, we observed that TET2 expression was significantly downregulated in patients with hepatocellular carcinoma, suggesting that tumour hypoxia may deregulate TET2 expression resulting in global changes in DNA hydroxymethylation.   Conclusion: Given the dramatic effects of nutrient availability on gene expression, future in vitro experiments should be aware of how excess levels of glutamine and glucose may perturb transcriptional responses.

Extreme physiological plasticity in a hibernating basoendothermic mammal, Tenrec ecaudatus.

Physiological plasticity allows organisms to respond to diverse conditions. However, can being too plastic actually be detrimental? Malagasy common tenrecs, Tenrec ecaudatus, have many plesiomorphic traits and may represent a basal placental mammal. We established a laboratory population of T. ecaudatus and found extreme plasticity in thermoregulation and metabolism, a novel hibernation form, variable annual timing, and remarkable growth and reproductive biology. For instance, tenrec body temperature (Tb) may approximate ambient temperature to as low as 12°C even when tenrecs are fully active. Conversely, tenrecs can hibernate with Tb of 28°C. During the active season, oxygen consumption may vary 25-fold with little or no change in Tb During the austral winter, tenrecs are consistently torpid but the depth of torpor may vary. A righting assay revealed that Tb contributes to but does not dictate activity status. Homeostatic processes are not always linked, e.g. a hibernating tenrec experienced a ∼34% decrease in heart rate while maintaining constant body temperature and oxygen consumption rates. Tenrec growth rates vary but young may grow ∼40-fold in the 5 weeks until weaning and may possess indeterminate growth as adults. Despite all of this profound plasticity, tenrecs are surprisingly intolerant of extremes in ambient temperature (<8 or >34°C). We contend that while plasticity may confer numerous energetic advantages in consistently moderate environments, environmental extremes may have limited the success and distribution of plastic basal mammals.

Reduction of glycemic variability with Degludec insulin in patients with unstable diabetes.

INTRODUCTION: Degludec (IDeg) is an ultralong-acting insulin, with stable pharmacodynamic profile which leads to lower fluctuations in glucose levels. The effect of IDeg has not been specifically assessed in patients with unstable diabetes, defined as increased glycemic variability (GV). METHODS: A prospective before-after pilot study was conducted, including patients managed at Hospital Universitario San Ignacio in Bogotá, Colombia. The impact of the switch from a Glargine or Detemir insulin to a basal insulin regimen with IDeg for 12 weeks on GV measured by continuous glucose monitoring, on A1c levels, and on the incidence of episodes of global and nocturnal hypoglycemia was assessed in a group of patients with (coefficient of variation >34%) or without increased basal GV using a Generalised Estimating Equation (GEE) analysis. RESULTS: 60 patients with basal bolus therapy and history of hypoglycemia were included. 18 patients had High GV (HGV). In this group a significant reduction of 11.1% of CV (95% CI: 6.3, 15.9, p = 0.01) was found. GEE analysis confirmed a higher impact over time on patients with HGV (p < 0.001). The percentage of patients with at least 1 episode of hypoglycemia decreased from 66.6% to 22.2% (p = 0.02) and from 37.14% to 5.71% (p < 0.01) for global and nocturnal hypoglycemia, respectively. Changes were not significant in patients with low GV. A reduction of A1c was observed in both groups (p < 0.001). CONCLUSIONS: The results suggest that treatment with IDeg reduces GV, A1c levels and the incidence of global and nocturnal hypoglycemia events in patients with HGV, but not in patients with low GV.

Nueva propuesta quirúrgica para úteros miomatosos grandes: histerectomía asistida inversa / New surgical approach for large fibroid uterus. Reverse assisted hysterectomy

Objetivo: describir una nueva técnica que combina la vía vaginal y la laparoscopia en caso de úteros grandes y con poca movilidad permitiendo evitar la vía laparotómica. Material y métodos: se realiza un estudio descriptivo y retrospectivo entre marzo de 2011 y abril de 2013. Se recogen 15 casos realizados con esta técnica en el Hospital de Mataró. Se analizan la edad, la paridad, número de cesáreas u otras cirugías anteriores ya fuesen abdominales o vaginales, estado hormonal de la paciente, tamaño uterino clínico y por ecografía, prolapso uterino, incontinencia de orina, hemoglobina pre y post quirúrgicas, sangrado durante la cirugía, peso por anatomía patológica, diagnóstico anatomopatológico y días de hospitalización. Resultados: la media de edad de las pacientes fue de 46,7 años. El motivo de consulta en el 53,3% de los casos fue por metrorragia y en el 46,7% por tumoración abdominal. El peso medio de las piezas quirúrgicas fue de 705 g y no hubo complicaciones importantes asociadas a la cirugía. La media de tiempo operatorio fue de 122 minutos. Conclusiones: si bien los avances en la vía laparoscópica han permitido realizar histerectomías de úteros miomatosos con éxito, dejando en un segundo plano la vía abdominal, todavía existen casos de úteros grandes con poca movilidad lateral que nos obligan a realizar un abordaje abdominal. Para estas situaciones, nuestro grupo, realiza una traquelectomía simple vía vaginal con posterior histerectomía subtotal vía laparoscópica. Se trata de una alternativa viable, segura, con una baja tasa de complicaciones y con una estancia hospitalaria reducida, por lo que parece una opción razonable en casos seleccionados (AU)

Objective: To describe a new technique that combines vaginally and laparoscopy approach for large and no-mobil uteri allowing to avoid laparotomy. Material and methods: A descriptive and retrospective study was performed between March 2011 and April 2013. 15 cases performed with this procedure in Mataró Hospital are collected. We analize age, parity , number of caesarean section or other previous surgeries (abdominal or vaginal), hormonal status of the patient, uterine size clinical and by ultrasound , uterine prolapse, urinary incontinence, pre and post surgical hemoglobin, bleeding during surgery, weight pathology, pathological diagnosis and hospital stay. Results: The average age of the patients was 46.66 years. The main reason for consultation in 53.33% of cases was for menorrhagia and in 46.66% of abdominal tumor. The average weight of the surgical specimens was 705 g and there were no major complications related to surgery. The mean operative time was 122 minutes. Conclusions: Despite of advances in laparoscopic approach for hysterectomies that have allowed us to perform successfully fibroid uterus, leaving in the background the abdominal route, there are still cases of large uteri with minimum lateral mobility that would make us think of a better abdominal approach. For these situations we propose the vaginal trachelectomy with subsequent laparoscopic subtotal hysterectomy is a feasible and safe alternative, with a low complication rate and a reduced hospital stay, it seems a reasonable option in selected cases (AU)

Los nuevos tipos de familias en el sistema sanitario / The new family types in the health system

Los cambios producidos en las familias españolas tienen una importancia decisiva en la planificación de los servicios sanitarios, en la evolución de sus demandas y en las relaciones con el personal sanitario. Se describen las características de las nuevas estructuras familiares (monoparentales, homoparentales, tardías, con embarazos múltiples, reconstituidas, adoptivas y que recurren a las técnicas de reproducción asistida), cuáles son sus preocupaciones, necesidades y demandas, y las repercusiones en el sistema sanitario (AU)

Changes in the Spanish families are critical in the planning of health services, in the evolution of their demands, and in their relationships with healthcare staff. We describe the characteristics of the new family structures (single-parent families, LGBT families, older families, multiple birth families, stepfamilies, adoptive families and families that resort to assisted reproductive techniques), what are their concerns, their needs and their requirements, and what are the implications for the health system (AU)

Continuous Glucose Monitoring Versus Capillary Point-of-Care Testing for Inpatient Glycemic Control in Type 2 Diabetes Patients Hospitalized in the General Ward and Treated With a Basal Bolus Insulin Regimen.

BACKGROUND: Continuous glucose monitoring (CGM) may improve the management of patients with type 2 diabetes hospitalized in the general ward by facilitating the detection of hyper- and hypoglycemic episodes. However, the lack of data on the accuracy and safety of CGM have limited its application. METHODS: A prospective pilot study was conducted including 38 patients hospitalized in the general ward with a known diagnosis of type 2 diabetes mellitus (DM) and hyperglycemic individuals without a history of DM with a blood sugar of 140-400 mg on admission treated with a basal bolus insulin regimen. Inpatient glycemic control and the incidence of hypoglycemic episodes were compared between detection by CGM of interstitial fluid for up to 6 days and point-of-care (POC) capillary blood glucose monitoring performed pre- and postprandially, before bedtime and at 3 am. RESULTS: No differences in average daily glucose levels were observed between CGM and POC (176.2 ± 33.9 vs 176.6 ± 33.7 mg/dl, P = .828). However, CGM detected a higher number of hypoglycemic episodes than POC (55 vs 12, P < .01). Glucose measurements were clinically valid, with 91.9% of patients falling within the Clarke error grid A and B zones. CONCLUSIONS: Our preliminary results indicate that the use of CGM in type 2 patients hospitalized in the general ward provides accurate estimation of blood sugar levels and is more effective than POC for the detection of hypoglycemic episodes and asymptomatic hypoglycemia.

Effects of performing morning versus afternoon exercise on glycemic control and hypoglycemia frequency in type 1 diabetes patients on sensor-augmented insulin pump therapy.

BACKGROUND: Although physical exercise (PE) is recommended for individuals with type 1 diabetes (DM1), participation in exercise is challenging because it increases the risk of severe hypoglycemia and the available therapeutic options to prevent it frequently result in hyperglycemia. There is no clear recommendation about the best timing for exercise. The aim of this study was to compare the risk of hypoglycemia after morning or afternoon exercise sessions up to 36 hours postworkout. METHODS: This randomized crossover study enrolled subjects with DM1, older than 18 years of age, on sensor-augmented insulin pump (SAP) therapy. Participants underwent 2 moderate-intensity exercise sessions; 1 in the morning and 1 in the afternoon, separated by a 7 to 14 day wash-out period. Continuous glucose monitoring (CGM) data were collected 24 hours before, during and 36 hours after each session. RESULTS: Thirty-five subjects (mean age 30.31 ± 12.66 years) participated in the study. The rate of hypoglycemia was significantly lower following morning versus afternoon exercise sessions (5.6 vs 10.7 events per patient, incidence rate ratio, 0.52; 95% CI, 0.43-0.63; P < .0001). Most hypoglycemic events occurred 15-24 hours after the session. On days following morning exercise sessions, there were 20% more CGM readings in near-euglycemic range (70-200 mg/dL) than on days prior to morning exercise (P = .003). CONCLUSIONS: Morning exercise confers a lower risk of late-onset hypoglycemia than afternoon exercise and improves metabolic control on the subsequent day.

[THE NEW FAMILY TYPES IN THE HEALTH SYSTEM]. / Los nuevos tipos de familias en el sistema sanitario.

Changes in the Spanish families are critical in the planning of health services, in the evolution oftheirdemands, and in their relationships with healthcare staff We describe the characteristics of the new family structures (single-parent families, LGBT families, older families, multiple birth families, stepfamilies, adoptive families and families that resort to assisted reproductive techniques), what are their concerns, their needs and their requirements, and what are the implications for the health system.

Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation.

BACKGROUND: Protein synthesis is tightly regulated and alterations to translation are characteristic of many cancers.Translation regulation is largely exerted at initiation through the eukaryotic translation initiation factor 4 F (eIF4F). eIF4F is pivotal for oncogenic signaling as it integrates mitogenic signals to amplify production of pro-growth and pro-survival factors. Convergence of these signals on eIF4F positions this factor as a gatekeeper of malignant fate. While the oncogenic properties of eIF4F have been characterized, genome-wide evaluation of eIF4F translational output is incomplete yet critical for developing novel translation-targeted therapies. RESULTS: To understand the impact of eIF4F on malignancy, we utilized a genome-wide ribosome profiling approach to identify eIF4F-driven mRNAs in MDA-MB-231 breast cancer cells. Using Silvestrol, a selective eIF4A inhibitor, we identify 284 genes that rely on eIF4A for efficient translation. Our screen confirmed several known eIF4F-dependent genes and identified many unrecognized targets of translation regulation. We show that 5'UTR complexity determines Silvestrol-sensitivity and altering 5'UTR structure modifies translational output. We highlight physiological implications of eIF4A inhibition, providing mechanistic insight into eIF4F pro-oncogenic activity. CONCLUSIONS: Here we describe the transcriptome-wide consequence of eIF4A inhibition in malignant cells, define mRNA features that confer eIF4A dependence, and provide genetic support for Silvestrol's anti-oncogenic properties. Importantly, our results show that eIF4A inhibition alters translation of an mRNA subset distinct from those affected by mTOR-mediated eIF4E inhibition. These results have significant implications for therapeutically targeting translation and underscore a dynamic role for eIF4F in remodeling the proteome toward malignancy.

Escala de sociotropía-autonomía (sas): propiedades psicométricas de la adaptación a colombia / Sociotropy-autonomy scale (sas): psychometric properties of adaptation to colombia

Este artículo presenta los resultados de una investigación cuyo objetivo fue adaptar y validar la Escala de Sociotropía-Autonomía (SAS) de Clark & Beck, la cual evalúa dos dimensiones de personalidad cognitiva: la orientación interpersonal y actitudes de logro y metas personales. La muestra consistió en 460 participantes entre 15 y 71 años, escolarizados de distintos estratos socioeconómicos. Los resultados mostraron índices de consistencia interna en la Escala SAS: total (,85), SAS Sociotropía (,82) y menores para SAS autonomía (,61). Estos resultados guardan relación con investigaciones acerca de este instrumento; por lo tanto se considera confiable y válido para el contexto sociocultural; además podría apoyar la investigación en psicoterapia cognitiva y en procesos clínicos basados en el modelo diátesis estrés.

This paper presents the results of a study whose aim was adapt and validate the Sociotropy-Autonomy Scale (SAS) Clark & Beck. This scale assesses two dimensions of cognitive personality: interpersonal orientation and attitudes of achievement and personal goals. The sample consisted of 460 participants between 15 and 71 years enrolled from different socioeconomic levels. The results showed internal consistency in SAS Scale: Total (.85), SAS Sociotropy (.82) and lower for SAS Autonomy (.61). These results are relevant to research on this instrument. It is considered a reliable and valid instrument for socio-cultural context; could also support research in cognitive psychotherapy and clinical processes based on the diathesis stress model.

Encefalitis por anticuerpos contra el receptor anti-N-metil-D-aspartato debido a teratoma ovárico / Anti-NMDA receptor encephalitis due to an ovarian teratoma

La presencia de anticuerpos dirigidos contra el receptor de N-metil-D-aspartato se ha asociado a un síndrome neurológico que se caracteriza por alteraciones de la consciencia, movimientos involuntarios y convulsiones. Se considera un síndrome paraneoplásico que se relaciona en las mujeres jóvenes con los tumores de ovario, pero puede ocurrir en ausencia de neoplasia. En la mayoría de los casos, la disautonomía, complejos movimientos involuntarios, hipertermia y insuficiencia respiratoria, requiere tratamiento en las unidades de cuidados intensivos. La resección del tumor conduce a la completa recuperación de las secuelas neurológicas a largo plazo (AU)

The presence of antibodies against the N-methyl-D-aspartate receptor has been associated with a neurological syndrome characterized by alterations of consciousness, involuntary movements, and seizures. These alterations are considered to be a paraneoplastic syndrome primarily associated with ovarian tumors in young women but can occur in the absence of neoplasia. In most patients, dysautonomia, complex involuntary movements, hyperthermia and respiratory failure require treatment in intensive care units. Tumoral resection of the tumor leads to complete neurological recovery in the long term (AU)