Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis.

When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.

Defining a standard set of health outcomes for patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. RESULTS: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). CONCLUSION: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.

Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients.

There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn's disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56-87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1-9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.

Gluteoplastia de aumento con implantes intramusculares para el mejoramiento del contorno corporal / Augmentation gluteoplasty with intramuscular implants to improve the physical measurement i:en

Introducción: La región glútea ha sido considerada una de las zonas más observadas tanto en mujeres como en hombres y constituye un ícono representativo de belleza corporal. En los últimos años se ha incrementado el deseo de las féminas de aumentar esta región anatómica con implantes. Objetivo: Determinar los resultados estéticos de la gluteoplastia de aumento con implantes intramusculares. Métodos: Se realizó un estudio prospectivo, longitudinal y descriptivo de 25 mujeres que acudieron a la consulta externa del Servicio de Cirugía Plástica del Hospital Clínico-Quirúrgico Hermanos Ameijeiras, desde agosto de 2016 hasta febrero de 2019, para solicitar el aumento de su región glútea con implantes. Resultados: En la serie predominaron el grupo etario de 31 a 40 años (36,0 %) y el fototipo de piel III (88,0 %); asimismo, solo 6 pacientes presentaron complicaciones (24,0 %), entre las cuales sobresalieron el seroma (20,8 %), la asimetría (12,5 %) y la dehiscencia de la sutura (8,3 %). Se observó un aumento significativo de la proyección glútea después de la intervención (α=0,05) y los resultados fueron buenos en la mayoría de las integrantes de la muestra (84,0 %). Conclusiones: La gluteoplastia de aumento con implantes intramusculares es un procedimiento seguro y ofrece resultados estéticos favorables.

Introduction: Gluteal region has been considered one of the most observed areas either in women as in men and constitutes a representative icon of corporal beauty. In the last years the desire of women to increase this anatomical region with implants has been increased. Objective: To determine the aesthetic results of the augmentation gluteoplasty with intramuscular implants. Methods: A prospective, longitudinal and descriptive study of 25 women that went to the Plastic Surgery Service outpatient consultation of Hermanos Ameijeiras Clinical Surgical Hospital was carried out from August, 2016 to February, 2019, to request the increase of the gluteal region with implants. Results: In the series there was a prevalence of the 31 to 40 age group (36.0%) and the skin phototype III (88.0%); also only 6 patients presented complications (24.0%), among which seroma (20.8%), asymmetry (12.5%) and anastomotic dehiscence (8.3%) were notable. A significant increase of the gluteal projection after the intervention was observed (α =0.05) and the results were good in most of the members of the sample (84.0%). Conclusions: The augmentation gluteoplasty with intramuscular implants is a safe procedure and offers favorable aesthetic results.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

End of life in patients attended by pediatric palliative care teams: what factors influence the place of death and compliance with family preferences?

Each year, more than 8 million children worldwide require specialized palliative care, yet there is little evidence available in pediatrics on the characteristics of the end of life in this context. Our aim is to analyze the characteristics of patients who die in the care of specific pediatric palliative care teams. This is ambispective, analytical observational, multicenter study conducted between 1 January and 31 December 2019. Fourteen specific pediatric palliative care teams participated. There are 164 patients, most of them suffering from oncologic, neurologic, and neuromuscular processes. The follow-up time was 2.4 months. The parents voiced preferences in respect of the place of death for 125 of the patients (76.2%). The place of death for 95 patients (57.9%) was at the hospital and 67 (40.9%) was at home. The existence of a palliative care team for over 5 years is more likely to be related to families voicing preferences and their fulfillment. Longer follow-up times by pediatric palliative care teams were observed in families with whom preferences regarding the place of death were discussed and in patients who died at home. Patients who did not receive home visits, when the pediatric palliative care team did not provide full care and when preferences regarding the place of death were not discussed with parents, were more likely to die in the hospital.   Conclusions: Advance planning of end-of-life care is one of the most important aspects of pediatric palliative care. The provision of services by the teams and the follow-up time are related to parents' expressed preferences and the place of death. What is Known: • Various studies have shown how the availability of pediatric palliative care services improves the quality of life of patients and their families while reducing costs. • The place of death is an important factor influencing the quality of end-of-life care for dying people. The increase in palliative care teams increases the number of deaths in the home and having this care available 24/7 increases the probability of dying at home. What is New: • Our study identifies how a longer follow-up time of patients by palliative care teams is significantly associated with death at home and with express and comply with the preferences expressed by families. • Home visits by the palliative care team increase the likelihood that the patient will die at her home and that the preferences expressed by the palliative care team families will be cared for.

[Multimodal anesthesia in a patient with Graves' disease and thyrotoxicosis: A case report]. / Anestesia multimodal en paciente con enfermedad de Graves y tirotoxicosis: reporte de caso.

Background: Hyperthyroidism is the increase in the synthesis and secretion of thyroid hormones. It is rare but serious in children and constitutes approximately 5% of all cases; 15% manifests before 10 years of age. The peak of presentation and the majority of cases (80%) are diagnosed around 10-15 years of age. Adolescence is usually the stage with the highest incidence and it is more frequent in women (5:1). Acute thyrotoxic crisis or thyroid storm is rare and only occurs in a poorly controlled hyperthyroid patient or in a hyperthyroid patient undergoing emergency surgery. It is manifested by fever, extreme tachycardia, tachyarrhythmia with atrial fibrillation, vomiting, diarrhea, agitation and mental confusion. Clinical case: 17-year-old adolescent with Graves' disease with uncontrolled clinical manifestations that did not respond to medical treatment and was scheduled for radical thyroidectomy. 35 points were obtained on the Burch and Wartofsky Scale. It was managed with general anesthesia, reducing stimuli for airway and regional control to reduce surgical stimuli. Adjuvant medications such as magnesium sulfate for intraoperative stability were used. Conclusion: Multimodal anesthesia managed to avoid thyroid storm, postoperative pain, as well as other complications.

Introducción: el hipertiroidismo es el incremento en la síntesis y secreción de hormonas tiroideas. Es raro pero grave en la edad pediátrica y constituye aproximadamente el 5% de todos los casos; el 15% se presenta antes de los 10 años. El pico de presentación y la mayoría de los casos (80%) se diagnostican hacia los 10-15 años. La adolescencia es la etapa de mayor incidencia y más frecuente en mujeres (5:1). La crisis tirotóxica aguda o tormenta tiroidea es rara y solo se presenta en un hipertiroideo mal controlado o en un paciente hipertiroideo intervenido de urgencia. Se manifiesta con fiebre, taquicardia extrema, taquiarritmia con fibrilación auricular, vómito, diarrea, agitación y confusión mental. Caso clínico: adolescente de 17 años con enfermedad de Graves con manifestaciones clínicas descontroladas, la cual no respondió a tratamiento médico y se programó para tiroidectomia radical. Se obtuvieron 35 puntos en la Escala de Burch y Wartofsky. Se manejó con anestesia general y fueron disminuyendo los estímulos para control de vía aérea y regional a fin de disminuir los estímulos quirúrgicos. Se usaron medicamentos adyuvantes como sulfato de magnesio para la estabilidad transoperatoria. Conclusión: la anestesia multimodal logró evitar la tormenta tiroidea, el dolor postoperatorio, así como otras complicaciones.

Parvicella tangerina gen. nov., sp. nov. (Parvicellaceae fam. nov., Flavobacteriales), first cultured representative of the marine clade UBA10066, and Lysobacter luteus sp. nov., from activated sludge of a seawater-processing wastewater treatment plant.

Two strains isolated from a sample of activated sludge that was obtained from a seawater-based wastewater treatment plant on the southeastern Mediterranean coast of Spain have been characterized to achieve their taxonomic classification, since preliminary data suggested they could represent novel taxa. Given the uniqueness of this habitat, as this sort of plants are rare in the world and this one used seawater to process an influent containing intermediate products from amoxicillin synthesis, we also explored their ecology and the annotations of their genomic sequences. Analysis of their 16S rRNA gene sequences revealed that one of them, which was orange-pigmented, was distantly related to Vicingus serpentipes (family Vicingaceae) and to other representatives of neighbouring families in the order Flavobacteriales (class Flavobacteriia) by 88-89 % similarities; while the other strain, which was yellow-pigmented, was a putative new species of Lysobacter (family Xanthomonadaceae, order Xanthomonadales, class Gammaproteobacteria) with Lysobacter arseniciresistens as closest relative (97.3 % 16S rRNA sequence similarity to its type strain). Following a polyphasic taxonomic approach, including a genome-based phylogenetic analysis and a thorough phenotypic characterization, we propose the following novel taxa: Parvicella tangerina gen. nov., sp. nov. (whose type strain is AS29M-1T=CECT 30217T=LMG 32344T), Parvicellaceae fam. nov. (whose type genus is Parvicella), and Lysobacter luteus sp. nov. (whose type strain is AS29MT=CECT 30171T=LMG 32343T).

Neural plasticity of the uterus: New targets for endometrial cancer?

Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle. Therefore, a precise understanding of nerve-cancer crosstalk and the contribution of the organ-intrinsic neuroplasticity, mediated by estrogen and progesterone, of the uterine is urgently needed. The development of new and innovative medicines for patients with endometrial cancer would increase their quality of life and health. This review compiles information on the architecture and function of autonomous uterine neural innervations and the influence of hormone-dependent nerves in normal uterus and tumor progression. It also explores new therapeutic possibilities for endometrial cancer using these endocrine and neural advantages.

Monitoring contamination of hazardous drug compounding surfaces at hospital pharmacy departments. A consensus Statement. Practice guidelines of the Spanish Society of Hospital Pharmacists (SEFH).

OBJECTIVE: To establish a series of recommendations based on available evidence for monitoring surface contamination in the areas devoted to compounding hazardous drugs in pharmacy departments. METHOD: Based on a literature search in the Medline and Embase databases (search period: January 2009 to July 2019), as well as on a review of standards and recommendations issued by different healthcare organizations, a committee of experts from the Spanish Society of Hospital Pharmacists defined a series of safe practices for handling hazardous drugs and monitoring compounding work surfaces. Recommendation decisions were adopted by consensus among the members of the expert group, considering the recommendations reviewed, the monitoring situation in Spanish hospital departments, and the associated costs. RESULTS: Ten recommendations were formulated, structured into eight sections. They include aspects related to the drugs to be monitored; the  areas to be monitored; when samples should be taken; risk determination and preparation of a sampling protocol; analytical techniques; contamination thresholds; and design of an action plan based on the sampling and decontamination results obtained. CONCLUSIONS: Surface monitoring allows hazardous drugs detection and evaluation of the effectiveness of current protocols for the safe handling of such drugs in hospital pharmacy departments. The evaluation should include an analysis of the efficacy of engineering controls, work practices and cleaning and decontamination processes.

Objetivo: Establecer unas recomendaciones, en base a la evidencia disponible, para la monitorización de la contaminación de superficies en las áreas de elaboración de medicamentos peligrosos de los Servicios de Farmacia.Método:A partir de una revisión bibliográfica en las bases de datos Medline y Embase desde enero de 2009 a julio de 2019, así como de la consulta de documentos de estándares y recomendaciones de organizaciones sanitarias, un comité de expertos de la Sociedad Española de Farmacia Hospitalaria ha definido una serie de prácticas seguras sobre manipulación de medicamentos peligrosos y monitorización de superficies de trabajo. Las decisiones de recomendación se tomaron por consenso entre el grupo de expertos teniendo en cuenta las recomendaciones encontradas, la situación en nuestro entorno y los costes asociados a la monitorización.Resultados: Se han definido 10 recomendaciones estructuradas en ocho secciones. Se incluyen aspectos relacionados con los medicamentos a  monitorizar; localizaciones a monitorizar; momento de la toma de muestras; determinación del riesgo y plan de muestreo; técnicas analíticas; umbrales de contaminación; plan de acción según los resultados del muestreo y descontaminación.Conclusiones: La monitorización de superficies permite determinar la presencia de medicamentos peligrosos y evaluar la eficacia del programa de manejo seguro de los mismos en los Servicios de Farmacia. La  evaluación debería incluir un estudio de la eficacia de los controles de  ingeniería, de las prácticas laborales y de los procesos de limpieza y descontaminación.

Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy.

High prevalence of placental-derived complications, such as preeclampsia and intrauterine growth restriction, has been reported in women with breast cancer (BC) treated with chemotherapy during pregnancy (PBC-CHT). AIM: To ascertain whether PBC-CHT is associated with an imbalance of angiogenic factors, surrogate markers for placental insufficiency, that could explain perinatal outcomes. METHODS: Prospective study between 2012 and 2016 in a single institution. Soluble fms-like tyrosine kinase (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) in maternal blood were assessed throughout pregnancy in 12 women with BC and 215 controls. RESULTS: Cancer patients were treated with doxorubicin-based regimes and with taxanes. Ten PBC-CHT (83%) developed obstetrical complications. At the end of the third trimester, significantly higher levels of sFlt-1; sFlt-1/PGF ratio, and sEng levels were observed in BC women as compared to controls. Moreover; there was a significant correlation between plasma levels of sFlt-1 and the number of chemotherapy cycles administered. Besides, more chemotherapy cycles correlated with lower birthweight and head circumference at birth. CONCLUSIONS: Women with BC treated during pregnancy showed an antiangiogenic state compatible with placental insufficiency. Angiogenic factors could be useful in the clinical obstetric management of these patients; although further studies will be required to guide clinical decision-making.

Comparative Cost Analysis Of Intravenous And Subcutaneous Administration Of Rituximab In Lymphoma Patients.

PURPOSE: The availability of different routes of administration of rituximab, with different dosing and times of infusion in the day care unit, raises the question of which formulation would be the best in terms of direct cost, particularly with the approval of new intravenous (IV) rituximab biosimilars. We aim to retrospectively compare the direct costs of IV and subcutaneous (SC) rituximab in lymphoma, considering drug cost, pharmacy handling and occupation in day care unit in Son Espases University Hospital during 2017, now that the IV biosimilar is available. PATIENTS AND METHODS: The data were collected from Oncosafety®-AVIDA for doses and SAP® for economic data. The costs of occupation are published by the Local Health Service. RESULTS: In 2017, 527 cycles were prescribed for 103 patients with lymphoma: 141 IV and 386 SC. Median doses were 690 mg and 1400 mg with a median cost of the drug of 1458.45€ and 1334.77€ for IV and SC routes, respectively. The nurse handling costs were 4.49€ and 2.24€, respectively. The cost of the day care unit occupation was 493€ and 123€, respectively. Overall, the median total cost per cycle was 1955.94€ for the IV, 1460.01€ for the SC and 1729€ for the biosimilar (p<0.001). The sensitivity analysis showed that it would be necessary for the cost of the IV biosimilar to be 34% lower than the price of SC rituximab to make a difference. CONCLUSION: This study shows a reduction in the cost with the administration of SC rituximab in real life compared with using the IV original rituximab and the biosimilar. This information is relevant for healthcare managers and administrations and applies only in the case of drugs with SC original presentations still not available in their correspondent biosimilars.

Comparison of commercial 5-aminolevulinic acid (Gliolan®) and the pharmacy-compounded solution fluorescence in glioblastoma.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) has become an important assistant in glioblastoma (GB) surgery. Unfortunately, its price affects its widespread use. OBJECTIVE: The aim of this study was to compare commercial 5-ALA with the pharmacy-compounded solution. METHODS: Using first an in vitro experimental approach, different concentrations of the pharmacy-compounded solution and commercial 5-ALA were tested in U87MG, LN229, U373, and T98G commercial glioblastoma cell lines. Fluorescence intensity was compared for each concentration by flow cytometry. Mean fluorescence of culture supernatant and lysate samples were analyzed. In a second phase, both preparations were used for surgical glioblastoma resection and tumor samples were analyzed by confocal microscopy. Mean fluorescence intensity was analyzed for each preparation and compared. RESULTS: There was a high variability of fluorescence intensity between cell lines, but each cell line showed similar fluorescence for both preparations (compounded preparation and commercial 5-ALA). In the same way, both preparations had similar fluorescence intensity in glioblastoma samples. CONCLUSION: Both, compounded and commercial 5-ALA preparations produce equivalent fluorescent responses in human glioblastoma cells. Fluorescence intensity is cell line specific, but fluorescent properties of both preparations are undistinguishable.

X-Linked Severe Combined Immunodeficiency and Hepatoblastoma: A Case Report and Review of Literature.

Severe combined immunodeficiency is an inherited disease with profoundly defective T cells, B cells, and natural killer cells. X-linked severe combined immunodeficiency is the most common form. In this report, we describe a 4-month-old male infant who was admitted to our hospital with progressive breathlessness and abdominal mass. He was diagnosed with hepatoblastoma and presented a pneumocystis jirovecii pneumonia at the beginning of chemotherapy. Definitive diagnosis of X-linked severe combined immunodeficiency was established by DNA analysis of the interleukin 2 receptor gamma chain gene. This case is the first report which describes an X-linked severe combined immunodeficiency patient with hepatoblastoma.

El uso de neumoperitoneo preoperatorio progresivo en el tratamiento de hernia gigante de la pared abdominal / (The use of progressive preoperative pneumoperitoneum as treatment in giant abdominal wall hernia)

Resumen La cirugía para la corrección de las hernias ventrales gigantes, con pérdida de domicilio abdominal, representa un reto importante debido a la gran cantidad de comorbilidades potenciales. En esta patología se produce una migración de los órganos abdominales hacia el saco herniario; eventualmente, se atrofian los elementos de la pared y al tratar de retornarlos a su posición normal, se puede provocar múltiples efectos adversos en el paciente. Por eso, se debe realizar una cuidadosa planificación, preoperatoriamente. El uso de neumoperitoneo preoperatorio progresivo, permite una adaptación más adecuada desde el punto de vista fisiológico, tanto a nivel sistémico, como en la capacidad abdominal, para tolerar el retorno de los contenidos que han perdido su domicilio. Se presenta aquí el caso de una paciente femenina de 58 años, con una hernia ventral gigante con pérdida de domicilio abdominal, en cuyo manejo se utilizó la introducción preoperatoria progresiva de neumoperitoneo, descrita por primera vez por Goñi Moreno, en 1940.

Abstract Surgery for the correction of giant ventral hernias, with loss of abdominal domain, represents a major challenge due to the large number of potential comorbidities. In this pathology there is a migration of the abdominal organs to the hernia sac; eventually, the elements of the wall undergo atrophy and when trying to return the organs to their normal position, it can cause multiple adverse effects in the patient. Therefore, a careful planning must be carried out preoperatively. The use of progressive preoperative pneumoperitoneum, allows a more adequate adaptation from the physiological point of view, both at a systemic level, as in the abdominal capacity, to tolerate the return of contents that have lost their domain. We present here the case of a 58 year old female patient, with a giant ventral hernia with loss of abdominal domain, in whose management, the introduction of progressive preoperative pneumoperitoneum was used, described for the first time by Goñi Moreno, in 1940.

Prevalencia de los trastornos temporomandibulares y factores asociados más comunes presentados en las clínicas de la Universidad Santo Tomás en el segundo periodo del año 2016 / Prevalence of the temporomandibular disorders and most common associated factors presented in the ninth and tenth semester clinics of the Universidad Santo Tomás in the second period of the year 2016

Objetivo: Establecer la prevalencia de los trastornos temporomandibulares (TTM) presentados por los pacientes que acudieron a las clínicas odontológicas de noveno y décimo semestre de la Universidad Santo Tomás en el segundo período de 2016. Materiales y Métodos: Se realizó un estudio observacional descriptivo de corte transversal, con una muestra de 113 historias clínicas, se recolectó la muestra de historias clínicas ya diligenciadas de las clínicas de noveno y décimo semestre de la Universidad Santo Tomás en el segundo periodo del año 2016. Usando estadística descriptiva para el análisis Univariado. En el análisis bivariado, se estableció relación entre TTM y las variables de interés mediante la prueba t-student y Chi-cuadrado donde un valor de p≤0,05 fue considerado estadísticamente significativo. Resultados: De las 113 historias clínicas se obtuvieron 131 diagnósticos, la prevalencia de uno o más TTM fue del 55,7%, de los cuales el 30,1% fueron mujeres diagnosticadas con TTM; el TTM más prevalente fue la subluxación unilateral en el 11,4% de los casos. De los factores asociados, predominó el ruido articular con 43,4% donde el tipo predominante de ruido fue el clic con 91,8%, seguido por el dolor muscular. Conclusiones: La prevalencia de TTM fue alta, representada en el 55,7% de la población. El TTM más común fue la Subluxación unilateral con un 11,4%. Se encontró asociación estadísticamente significativa entre al menos un factor de tipo signo y síntoma, los factores dentales y uno o más TTM.

Aim: To establish the prevalence of temporomandibular disorders (TMD) presented by patients who attended the dental clinics of the ninth and tenth semester of the Santo Tomas University in the second period of 2016. Materials and Methods: A cross - sectional, observational, descriptive study was carried out, with a sample of 113 clinical records. The sample was collected from clinical records already completed from the clinics of ninth and tenth semester of the University Santo Tomas in the second period of the 2016. Using descriptive statistics for the univariate analysis. In the bivariate analysis, a relationship between TMD and the variables of interest was established using the t-student and Chi-square test, where a value of p≤0.05 was considered statistically significant. Results: Of the 113 clinical records, 131 diagnoses were obtained. The prevalence of one or more TMD was 55.7%, of which 30.1% were women diagnosed with TMD. The most prevalent TTM was the unilateral subluxation in 11.4% of the cases. Of the associated factors, joint noise predominated with 43.4% where the predominant type of noise was the click with 91.8%, followed by muscle pain. Conclusions: The prevalence of TMD was high, represented in 55.7% of the population. The most common TMD was unilateral Subluxation with 11.4%. We found a statistically significant association between at least one sign and symptom type factor, dental factors and one or more TMD.

Increased secretory sphingomyelinase activity in the first trimester of pregnancy in women later developing preeclampsia: a nested case-control study.

The pathogenic basis of abnormal placentation and dysfunction in preeclampsia (PE) is highly complex and incompletely understood. Secretory sphyngomyelinase activity (S-ASM) was analyzed in plasma samples from 158 pregnant women developing PE and 112 healthy pregnant controls. Serum PlGF, sFlt-1, s-Endoglin and sVCAM were measured. Results showed S-ASM activity to be higher in women who later developed PE than in those with uncomplicated pregnancies (40.6% and 28.8% higher in the late- and early-onset groups, respectively). Plasma S-ASM activity correlated significantly with circulating markers of endothelial damage in the late-PE group (endoglin and sVCAM-1), with plasma cholesterol and total lipid levels. However, these significant associations were not observed in the early-PE or control groups. This work provides the first evidence of significantly elevated circulating S-ASM activity in the first trimester of pregnancy in women who go on to develop PE; thus, it may be deduced that the circulating form of ASM is biologically active in PE and could contribute to promoting endothelial dysfunction and cardiovascular programming. Plasma S-ASM measurement may have clinical relevance as a further potential biomarker contributing to the earliest identification of women at risk of developing preeclampsia.

Angiogenic Gene Expression in Down Syndrome Fetal Hearts.

INTRODUCTION: Forty percent of Down syndrome (DS) fetuses have congenital heart defects (CHD). An abnormal angiogenic environment has been described in euploid fetuses with CHD. However, the underlying pathophysiologic pathway that contributes to CHD in DS remains unknown. The objective was to compare the expression of angiogenic factors and chronic hypoxia genes in heart tissue from DS and euploid fetuses with and without CHD. METHODS: The gene expression profile was determined by real-time PCR quantification in heart tissue from 33 fetuses with DS, 23 euploid fetuses with CHD and 23 control fetuses. RESULTS: Angiogenic factors mRNA expression was significantly increased in the DS group compared to the controls (soluble fms-like tyrosine kinase-1, 81%, p = 0.007; vascular endothelial growth factor A, 57%, p = 0.006, and placental growth factor, 32%, p = 0.0227). Significant increases in the transcript level of hypoxia-inducible factor-2α and heme oxygenase 1 were also observed in the DS group compared to the controls. The expression of angiogenic factors was similar in DS fetuses and CHD euploid fetuses with CHD. CONCLUSION: Abnormal angiogenesis was detected in the hearts of DS fetuses with and without CHD. Our results suggest that DS determines an intrinsically angiogenic impairment that may be present in the fetal heart.

Intracellular oxidant activity, antioxidant enzyme defense system, and cell senescence in fibroblasts with trisomy 21.

Down's syndrome (DS) is characterized by a complex phenotype associated with chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic features of DS, such as premature aging. Using cultured fibroblasts with trisomy 21 (T21F), this study aimed to ascertain whether an imbalance exists in activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2, glutathione-peroxidase, and catalase during the cell replication process in vitro. T21F had high SOD1 expression and activity which led to an interenzymatic imbalance in the antioxidant defense system, accentuated with replicative senescence. Intracellular ROS production and oxidized protein levels were significantly higher in T21F compared with control cells; furthermore, a significant decline in intracellular ATP content was detected in T21F. Cell senescence was found to appear prematurely in DS cells as shown by SA-ß-Gal assay and p21 assessment, though not apoptosis, as neither p53 nor the proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These novel findings would point to a deleterious role of oxidatively modified molecules in early cell senescence of T21F, thereby linking replicative and stress-induced senescence in cultured cells to premature aging in DS.