In vitro activation of ovarian cortex and autologous transplantation: A novel approach to primary ovarian insufficiency and diminished ovarian reserve.

BACKGROUND: Primary ovarian insufficiency (POI) and diminished ovarian reserve are two conditions that affect women's fertility. Oocyte donation remains an option for these patients; however, the development of certain novel technologies, such as in vitro activation of ovarian cortex (IVA), enables the possibility of activating the pool of resting primordial follicles, increasing the chance of pregnancy. OBJECTIVE AND RATIONALE: Here, we review the main pathways (PI3K and Hippo signaling) that govern the activation of primordial follicles and its application through the development of culture systems that support ovarian cortex for autologous transplantation. We also review the available data from case reports regarding outcomes of pregnancy and live birth rates with IVA. SEARCH METHODS: A PubMed search was conducted using the PubMed-NCBI database to identify literature pertinent to the pathways involved in the activation of primordial follicles and the outcomes of IVA techniques from 2013 to the present. OUTCOMES: Women with POI have around a 5% chance of spontaneous pregnancy. Recently, novel techniques involving the activation of primordial follicles through molecular pathways have been developed, thus increasing the odds of these patients. More recently, the introduction of a drug-free IVA technique has shown to increase the number of antral follicles with successful oocyte maturation after gonadotropin treatment, reaching pregnancy rates over 30%, either through spontaneous conception or by the implementation of assisted reproductive technology. LIMITATIONS: The evidence of this review is based on a few small series, so data should be interpreted with caution, and only randomized controlled trials could estimate the real magnitude and success of the procedure. REASONS FOR CAUTION: IVA technique remains an experimental strategy, with limited available data and the requirement of invasive procedures. Moreover, possible carcinogenic effects not yet determined after transplantation require special caution. WIDER IMPLICATIONS: In view of the results achieved, IVA could provide a promising option for the preservation of fertility in some cancer patients and prepuberal girls where the only alternative is tissue cryopreservation. STUDY FUNDING/COMPETING INTERESTS: The authors received no specific funding for this work and declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

Sexto reporte de eventos adversos con tratamientos biológicos en Argentina: Informe del registro BIOBADASAR / Sixth report of adverse events with biological treatments in Argentina: Report of the BIOBADASAR registry

Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.

Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.

Accesibilidad y adherencia a drogas biológicas en un servicio público de reumatología de la ciudad de Rosario, Santa Fe, Argentina / Accessibility and adherence to biological drugs in a public rheumatology service in the city of Rosario, Santa Fe, Argentina

Objetivo: Describir la situación de accesibilidad y adherencia a tratamientos con drogas biológicas en pacientes de un servicio público de reumatología. Métodos: Estudio de corte transversal, observacional y retrospectivo que incluyó pacientes con gestión de DB. Variables: sociodemográficas, clínicas, tratamientos, tiempo desde el diagnóstico al acceso, adherencia (porcentaje de toma mensual y adecuada de la droga ≥75%); tiempo desde prescripción a administración; trámite administrativo realizado por entidad pública u obra social; certificado único de discapacidad (CUD). Resultados: Se incluyeron 57 pacientes, 86% mujeres, edad media 47,79 años (IC 95%: 44,46-51,12); educación media 8,42 años (IC 95%: 7,68-9,16); 82,5% nivel socioeconómico medio-bajo; 63,2% etnia mestiza; 19,3% cobertura privada. Patología más frecuente: artritis reumatoidea. Tiempo medio desde el diagnóstico a la DB: 104,25 meses (IC 95%: 82,61-125,89). Tiempo medio desde la prescripción a la aplicación: 6,4 meses (IC 95%: 5,62-7,18). Adherencia del 86,0%. 50% de los pacientes contaban con CUD. No hubo diferencias en el tiempo de espera desde prescripción a administración de DB, en relación a cobertura de salud (p=0,065) y nivel socioeconómico. Conclusión: Existe un largo tiempo de evolución de la enfermedad en relación a la accesibilidad a DB y tanto el acceso como la adherencia reflejan la vulnerabilidad de estos pacientes.

Objective: To describe the situation of accessibility and adhesion treatment of patients with biological drugs (BD) from a public rheumatology service. Methods: Cross-sectional, observational and retrospective study, which includes patients who have been treated with BD. Variables: sociodemographic; clinical and treatments; time from diagnosis to BD access, adherence (monthly intake percentage of the drug ≥75%); time from the prescription to the administration of the BD; paperwork by a public or private entity; disability certificate (DC). Results: A total of 57 patients were included, 86% women, mean age being 47.79 (95% CI: 44.46-51.12) and education years being 8.42 (95% CI: 7.68- 9.16). 82.5% belonged to a medium-low socioeconomic status and 63.2% were mestizos. 19.3% had private coverage. Rheumatoid Arthritis was the most frequent disease. The mean time from diagnosis to BD: 104.25 months (95% CI: 82.61-125.89). The mean time from prescription to application: 6.4 months (95% CI: 5.62-7.18). The adherence was 86.0% and 50.0 % of patients had DC. There were no differences in the waiting time from the prescription to BD administration, taking into account the health coverage (p = 0.065) and socioeconomic status. Conclusion: There is a long time of disease evolution in regarding the accessibility to BD. In addition, accessibility and adherence reflect the vulnerability of our patients.

Analysis of Indications and Results in Liver Retransplantation: Is Late Retransplantation Worthwhile?

BACKGROUND: Liver retransplantation (LrT) is the only therapeutic option for irreversible hepatic graft failure. Despite various improvements, its technical complexity entails a greater morbidity in the short and long term. The main goal of the study was to analyze the activity of LrT at our center, as well as its indications, timing, postoperative evolution, and the long-term survival of patients. METHODS: We designed a descriptive study of a cohort of patients who underwent LrT in a Spanish Hepatic Transplant Unit, between April 1, 2002 and December 31, 2015. RESULTS: A total of 366 primary orthotopic liver transplantations were performed, 20 of which were LrTs, resulting in a 5.5% retransplantation rate. The most frequent indication for LrT was hepatic artery thrombosis (HAT) (35%). Twenty-five percent of the LrTs were early retransplantations and 75% were late retransplantations. After LrT, 35% of the grafts showed liver dysfunction. The overall mortality rate was 45%: in early LrT this was 25% and in late LrT it was 46.7%. Graft actuarial survival at 1 month post-LrT was 75% and at 5 years it was 63.6%. The overall actuarial survival after LrT at month 1, year 1, year 3, and year 5 was 80%, 69.6%, 58.9%, and 50.5%, respectively. In the late LrT group, the results proved less favorable, so it is necessary to define the minimum acceptable result before proceeding to a second graft. CONCLUSION: Our LrT rate was lower than that reported by other groups in our country. The actuarial survival rates for graft and patient are comparable to those obtained by other groups.

Magnetic resonance imaging findings in epileptic cats with a normal interictal neurological examination: 188 cases.

Epilepsy is a common neurological condition in dogs and cats. Although an increased likelihood of significant brain lesions with age has been identified in neurologically normal dogs with epileptic seizures, the underlying aetiology of epileptic seizures in cats that present with normal physical and neurological examinations remains unknown. In this cross-sectional study, the authors examined MRI findings in a large population of cats with a normal interictal physical and neurological examination. They hypothesised that age would have an impact on the prevalence of detectable lesions. First, following the guidelines for dogs and in accordance with previous studies, the authors divided the cats into three age groups (aged one year or younger, between one and six, and older than six) and calculated the proportion of cats with a detectable lesion on MRI in these groups. In the first group, 3/32 cats (9.4 per cent) had significant MRI abnormalities that were all consistent with congenital malformation; in the second group, only 5/92 (5.4 per cent) MRI scans were abnormal and in the third group, 15/ 65 (23.1 per cent) cats showed abnormal findings that were predominantly lesions of neoplastic origin. Second, to investigate the impact of age further, data were investigated as a continuous variable using receiver operating characteristic analysis. This indicated an optimal cut-off age of five years, above which MRI abnormalities were more likely, with an increase in the odds of a significant structural lesion increasing by 14 per cent per year.

Suspected air embolism through the thoracic ventral internal vertebral venous plexus during hemilaminectomy in dogs.

Venous air embolism entering via the ventral internal vertebral venous plexus was suspected during thoracic spinal surgery in two dogs. In both cases, air was seen bubbling from a pool of blood on the floor of the vertebral canal accompanied by sudden cardiopulmonary disturbances: low end-tidal carbon dioxide pressure, tachycardia and reduction in oxygen in the blood. One dog became dyspnoeic and one died.

Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele.

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC. METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated. RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment. CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Synthesis of tubular nanostructures from wheat bran albumins during proteolysis with V8 protease in the presence of calcium ions.

There are very few reports on the self-assembly of peptides derived from proteins of agro industrial byproducts origin. Although it has been claimed that purity is a determining factor in peptide self-assembly, whether proteins extracted using water along with other components also form self-assembled structures is not known. The results of this work prove that albumins from wheat bran, a byproduct obtained from the milling industry, can form tubular nanostructures during their hydrolysis with the V8 protease in the presence of Ca(2+). Electron microscopy of the hydrolysate revealed that under specific conditions, long filaments are formed, which are nanotubes of several microns in length, with inner and outer diameters of 100 and 200 nm, respectively. The infrared analysis of the hydrolysate identified (-)OOC-Ca(2+) interactions and changes in beta sheet content in response to variations in protein/V8/Ca(2+) molar ratios. A model that explains the probable mechanism of the observed self-assembly is discussed.

Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Osseous associated cervical spondylomyelopathy at the C2-C3 articular facet joint in 11 dogs.

In dogs, vertebral canal stenosis at C2-C3 due to articular facet joint degeneration is only sporadically identified. The authors' aims were to review the clinical presentation, MRI characteristics, treatment and outcome of dogs presenting with this condition. Eleven cases were eligible for inclusion. Neurological examination revealed tetraparesis and proprioceptive ataxia in all 4 limbs in 3/11, proprioceptive tetra-ataxia only in 4/11, pelvic limb proprioceptive ataxia in 2/11 and no gait abnormalities in 2/11 dogs. Cervical hyperaesthesia was present in 7/11 dogs. MRI revealed bilateral articular facet joint degeneration in 10/11 cases and unilateral degeneration in one. Surgery was performed in six cases and medical management elected in five. Long-term follow-up information was available for 11 animals. Four of the surgical cases are alive and have no neurological deficits, one was euthanased for an unrelated condition and one lost to follow-up. Of the cases managed medically, three are alive showing no neurological deficits, one is alive still displaying neurological deficits and one euthanased for an unrelated condition whilst still ataxic. This study shows that both medical and surgical management can result in good outcomes in dogs with vertebral canal stenosis resulting from articular facet joint degeneration at the level of C2-C3.

Diagnostic Exercise: Circling and Behavioral Changes in a Cat.

A 4-year old spayed male domestic shorthair cat was presented with a history of circling and behavioral changes. Neurologic examination showed mild proprioceptive deficits. The lesion was localized in the forebrain, and magnetic resonance imaging revealed the presence of a large midline intracranial mass extending from the frontal lobe to the tentorial region of the brain. Euthanasia was elected due to poor prognosis. Histopathologic evaluation confirmed the presence of a mass composed by sheets and aggregates of large round/polygonal cells and multinucleate cells associated with deposits of cholesterol clefts, scattered hemorrhages and hemosiderin-laden macrophages. Immunohistochemistry showed that the round/polygonal cells and multinucleate cells were strongly positive for major histocompatibility complex class II antigen, variably positive for CD18, and occasionally positive for S100. Subsets of spindle cells showing variable expression of vimentin, S100, and neuron-specific enolase were also present. The final diagnosis was cholesterol granuloma. Differential diagnosis with meningioma is discussed.

Exaggerated placental site/placental site trophoblastic tumor: an underestimated risk factor for emergency peripartum hysterectomy.

OBJECTIVE: To assess the indications and possible underlying causes of emergency peripartum hysterectomy (EPH) at the present hos- pital during the 2001-2011 period. MATERIALS AND METHODS: A revision of the charts and pathology reports corresponding to 42,728 parturients. RESULTS: During the study period, 25 peripartum hysterectomies were performed (0.61/1.000), of which 23 were EPHs (0.54/1.000) and two were planned cesarean hysterectomies. The indication for EPH was acute postpartum hemorrhage in 22 of 23 instances (95.7%). Roughly two-thirds of the operated uteri (16/25, 64%) showed placental site anomalies, half corresponding to different degrees of placental accretism and half to anomalies derived from the implantation site intermediate trophoblast. In five cases (31%), the anomaly was an exaggerated placental site and three cases corresponded to placental site trophoblastic tumors. Of the 16 cases showing placental site anomalies, ten (62.5%) were associated with one or more previous cesarean sections. CONCLUSIONS: Roughly one-third of EPHs performed at the present center during the last ten years were associated with placental site anomalies originating in the implantation site intermediate trophoblast (exaggerated placental site and placental site trophoblastic tumor). This association has not been described before, and should be taken into consideration when facing acute peripartum hemorrhage predisposing to EPH.

Tercer reporte de eventos adversos con tratamientos biológicos en Argentina. Informe de registro biobadasar / Thrid report of adverse events with biologics in Argentina. Report from biobadasar registry

Introducción: BIOBADASAR (Registro Argentino de Eventos Adversos con Tratamientos Biológicos en Reumatología) comenzó en agosto de 2010. La importancia de este registro es mostrar datos locales que, probablemente, puedan diferir de otros registros. El objetivo es comunicar los resultados del tercer reporte de BIOBADASAR. Métodos: Todos los pacientes con enfermedades reumáticas que requirieron tratamiento con agentes biológicos y pacientes controles sin estos tratamientos fueron incluidos en la base de datos provenientes de 32 centros participando a lo largo de la Argentina. Tres áreas de datos son analizados: características de los pacientes, tratamientos y eventos adversos...

Introduction: BIOBADASAR (Argentine Registry of Adverse Events with Biological Treatments in Rheumatology) began in August 2010. The importance of this registry is to show local data that may probably differ from other registries. The objective is to communicate the results of the third BIOBADASAR report. Methods: All patients with rheumatic diseases who required treatment with biological agents and control patients without these treatments were included in the database from 32 participating centers throughout Argentina. Three areas of data are analyzed: patient characteristics, treatments and adverse events...

Características generales y factores predictores de mortalidad hospitalaria en pacientes con asistencia ventilatoria mecánica / General characteristics and predictive factors of Hospital mortality in patients with assistance mechanical ventilation

Objetivo: Estudiar características generales y factores predictores de mortalidad hospitalaria en pacientes internados en Unidad de Terapia Intensiva (UTI) que requirieron Asistencia ventilatoria mecánica (AVM).Diseño: Estudio prospectivo, observacional, 36 meses de duración. Ámbito: Terapia intensiva polivalente. Hospital universitario. Pacientes: AVM ≥24 horas. Variables de interés: Datos demográficos; tipo de patología de ingreso a UTI; tiempo de internación en UTI y hospital; escores al ingreso, PCR (mg/dl); AVM: motivo de inicio, permanencia y complicaciones asociadas; evolución. Resultados: 372 pacientes requirieron AVM. Edad media 52 años (r 18-93), 67% eran varones. Estadía en UTI fue 12,59 (±13,52) días y Hospital de 20,31 (±25,20). 53,2% fallecieron en UTI. Se realizó comparación de variables entre sobrevivientes y fallecidos. Análisis de regresión logística múltiple se incluyeron: edad, PCR, APACHE II, SAPS II, SOFA, patología médica, insuficiencia respiratoria y utilización de vasopresores. Mayor valor predictivo fueron: edad, patología médica, uso de vasopresores y PCR. (D de Sommer = 0,59). Sensibilidad: 68,15% (60,18 - 75,22), especificidad: 75,35% (68,93 - 80,84), VPP 66,88% (58,94 - 73,99), VPN 76,42% (70,01­ 81,84). La curva COR presenta un AUC de 0,793 (IC 95%: 0,747-0,839) p = 0,000.Conclusiones: Factores predictores de mortalidad fueron: edad (p=0,007), utilización de vasopresores (p=0,000) y patología médica (p=0,002). PCR, mostró un valor de p cercano al valor de significación (p=0,065).(AU)

Objective: Examining the general characteristics and predictive factors of inhospital mortality in patients in Intensive Care Unit (ICU) who needed mechanical ventilatory support (MVS). Design: Prospective and observational study, 36 months duration. Area: Multipurpose intensive therapy. University hospital. Patients: MVS≥24 hours. Variables of interest: Demographic data, type of pathology on admission to ICU, hospitalization time, scoring, C - reactive protein (CRP) (mg/dl), MVS: reason for initiation, duration and complications associated; evolution. Results: 372 of the patients required MVS, average age was 52 years old (r 18-93), 67% were men. Intensive care unit length of stay was 12, 59 (±13, 52) days and hospital length of stay was 20, 31 (±25, 20). 53,2% died in ICU. A comparison of variables between survivors and deceased was made. Multiple logistic regression (MLR) analysis included: age, PCR, APACHE II, SAPS II, SOFA, medical condition, respiratory failure and use of vasopressors. The greatest predictive value was: age, medical condition, use of vasopressors and PCR. (Sommer´s D = 0,59). Sensitivity 68,15% (60,18 - 75,22), specificity: 75,35% (68,93 - 80,84), VPP 66,88% (58,94 - 73,99), VPN 76,42% (70,01­ 81,84). AUC of ROC was 0,793 (IC 95%: 0,747-0,839) p = 0,000. Conclusion: Predictive factors of mortality were: age (p=0,007), use of vasopressors (p=0,000) and medical condition (p=0,002). CRP showed a p-value close to a significance value of (p=0,065).(AU)

CYLD regulates keratinocyte differentiation and skin cancer progression in humans.

CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies.

Organochlorine pesticide levels in adipose tissue of pregnant women in Veracruz, Mexico.

DDT and Lindane (gamma-HCH) which were used until 1999 in Mexico, have provided great benefits in the combat of vectors that spread infection-borne diseases and in agriculture for crop protection. The persistence in the environment and their accumulative properties results in bioconcentration in lipid rich tissues of the human body that reflect the extent of environmental pollution. Human adipose tissue samples were taken during 2009 from abdominal cavities of 69 pregnant women by cesarean surgery and from 34 samples of control donors by autopsy in Veracruz State. The samples were analyzed by gas chromatography with ECD. The results of mean levels (mg/kg on fat basis) were higher in controls compared to pregnant women beta-HCH 0.064 vs 0.027; pp'DDE 1.187 vs. 0.745; op'DDT 0.016 vs. 0.011; pp'DDT 0.117 vs. 0.099 and Sigma-DDT 1.337 vs. 0.854. The pregnant women group was divided according to age: up to 20, 20-30, and more than 30 years, and presented an increase for the more persistent pesticides with age in terms of mean concentrations and a more pronounced higher correlation in medians levels. Pairing Body Mass Index to organochlorine pesticide mean levels revealed no correlation between these factors in pregnant women.

Parathyroid hormone-related protein regulates the growth of orthotopic human lung tumors in athymic mice.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) has growth regulatory effects for many malignant cells and may influence the progression of carcinomas of the breast, prostate, and lung. In the current study, the authors investigated the in vivo and in vitro effects of PTHrP neutralizing antibody and PTHrP treatment on the growth of BEN cells, a human lung squamous cell carcinoma line that expresses PTHrP and its receptor. METHODS: Orthotopic lung tumors were produced in 20 athymic mice with BEN-GFP cells (a clonal line that stably expresses green fluorescent protein [GFP]) by instilling suspensions of 3 x 10(6) cells per mouse into the lungs of anesthetized animals. The mice were divided into 2 groups receiving either subcutaneous mouse antihuman PTHrP antibodies or irrelevant mouse immunoglobulin (Ig) G (150 microg) twice weekly. RESULTS: After 30 days, 6 of 10 mice receiving anti-PTHrP antibodies had lung tumors visible on macroscopic inspection, but only 1 of the 10 mice treated with irrelevant IgG had a lung tumor that was of that size (P < 0.01). GFP fluorescence was significantly greater in lung homogenates of the PTHrP antibody-treated mice than in the mice treated with IgG (6006 +/- 411 vs. 2907 +/- 282 relative fluorescent units, respectively; P < 0.001). Although neutralizing antibodies stimulated BEN cell lung tumor growth, exogenous PTHrP 1-34 treatment (0.01-1 nM) inhibited the growth of cultured BEN cells by approximately 40%. CONCLUSIONS: Although PTHrP expression has been reported to be associated with more aggressive malignancies, the data from the current study suggest that PTHrP 1-34 was a paracrine growth inhibitor in BEN human lung carcinoma cells. The growth-related effects of PTHrP are complex, and can be both stimulatory and inhibitory.