Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications.

BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN: A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). CONCLUSION: Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages.

Hiperfrecuentacion en Incapacidad Temporal en una empresa socio-sanitaria de las Islas Baleares (España). Variables relacionadas / High-frequency Temporary Disability in a socio-sanitary company of the Balearic Islands (Spain). Related Variables

Objetivos: La Incapacidad Temporal en España tiene una gran transcendencia por su repercusión socio-económica en las empresas y en la sociedad. Interesa conocer las variables que puedan influenciarla para poder actuar preventivamente y minimizar sus repercusiones. Material y Métodos: estudio descriptivo y retrospectivo de los procesos de IT en trabajadores de una empresa del sector socio-sanitario durante 1994-2010 y relación con variables sociodemográficas y laborales. Se emplea el paquete SPSS 20.0. Resultados: Se analizaron 12.516 procesos de IT, que se han producido en 1895 personas. Los trabajadores incluidos en el primer tercil pueden considerarse trabajadores hiperfrecuentadores y han sido responsables del mismo número de procesos, la misma duración y el mismo coste que los de los otros 2 terciles. Conclusiones: Son trabajadores hiperfrecuentadores: en procesos 159 personas (8,4%) con un tercio de los procesos (4179), en duración 104 personas (5,5%) un tercio de los días de IT (14.301) y en costes 102 personas (5,4%) un tercio del coste (13.086.333€) (AU)

Objectives: The Temporary Disability in Spain has a great transcendence for its socio-economic repercussion in companies and in society. It is important to know the variables that can Influence it so that it can act preventively and minimize its repercussions. Material and methods: descriptive and retrospective study of the Temporary Disability processes in workers from a socio-sanitary company during 1994-2010, its relation with sociodemographic variables and labour. The SPSS 20.0 package is used. Results: A total of 12,516 Temporary Disability processes were analysed, involving 1895 people. The workers included in the first tertile can be considered as hyper frequent workers and have been responsible for the same number, the same length and the same cost than those of the other 2 tertiles. Conclusions: High-frequency workers: In processes 159 people (8.4%) one third of the processes (4179), in duration 104 people (5.5%) one third of the Temporary Disability days (14,301) and in costs 102 people (5.4%) one third of the cost (€ 13.086.333) (AU)

Recurrent venous thrombosis in Ehlers-Danlos syndrome type III: an atypical manifestation.

Ehlers-Danlos syndrome (EDS) comprises a group of hereditary connective tissue disorders in which collagen synthesis and fibrogenesis are impaired. Patients with EDS type III have a bleeding tendency manifested by ecchymoses and haematomas. However, thrombotic events are rare in this entity. Herein, we present a 48-year-old Hispanic man with EDS type III who had recurrent cephalic vein thrombophlebitis and thrombosis, and brachial vein thrombosis. Tests for hypercoagulable disorders including antithrombin III activity, protein C activity, protein S activity, anticardiolipin antibodies, homocysteine levels, factor V Leiden mutation and prothrombin gene mutation were negative. The patient required long-term anticoagulation with warfarin. After 3 years follow-up, he did not present further thrombotic events. Clinicians should be aware that patients with EDS might be at risk for hypercoagulable disorders.

Multicenter phase II clinical trial of preoperative capecitabine with concurrent radiotherapy in patients with locally advanced rectal cancer.

INTRODUCTION: To assess pathologic complete response, sphincter preservation rates and toxicity profile of preoperative chemoradiation with capecitabine in resectable locally advanced rectal cancer. MATERIALS AND METHODS: Fifty-eight patients from six Spanish centers were included (March 2004 to June 2005) with histological/cytological diagnosis of locally advanced rectal cancer, age between 18 and 80 years, ECOG 0-2, adequate bone marrow, renal and hepatic functions. Prior chemotherapy/radiotherapy was not allowed. Preoperative treatment was capecitabine 825 mg/m(2) bid concomitant to radiotherapy (45 + 5.4 Gy boost over 5.5 weeks). Surgery was performed 4-8 weeks after completion of chemoradiotherapy. RESULTS: Fifty-eight patients were enrolled in this study: 60.3 % males, median age of 64.5 (30.9-78.7) years, 28.6 % with ECOG 0 and 71.4 % with ECOG 1. Median distance of tumor from the anal verge was 7 (1-12) cm. Fifty-two (89.6. %) patients completed preoperative chemoradiotherapy. Primary tumor and node downstaging occurred in 61.1 and 69.6 % of patients, respectively. Surgery was performed in 55 patients (94.8 %): 80 % had negative lymph nodes and 72.7 % underwent sphincter-preserving procedures. A pathologic complete response was observed in 10.5 % (95 % CI 2.5-18.5) of the patients. Main grade I-II toxicities were leucopenia (43.1 %), neutropenia (24.1 %), anemia (36.2 %), diarrhea (32.8 %) and skin disorders (5.1 %), from which diarrhea (6.9 %), leucopenia (1.7 %) and skin disorders (1.7 %) reached grade III. There were no grade IV toxicities. CONCLUSIONS: Preoperative capecitabine-based chemoradiation is a well-tolerated and effective neoadjuvant treatment for locally advanced rectal cancer that achieves encouraging rates of tumor downstaging.

Pulmonary hemorrhage in a patient initially presenting with discoid lupus.

As a cutaneous variant of lupus erythematosus, discoid lupus erythematosus (DLE) is thought to have a good prognosis; however, the involvement of internal organs with a transition to systemic disease may occur. The progression from DLE to systemic lupus erythematosus has been reported in up to 28% of patients. This progression to systemic disease has been associated with a benign course. Herein, we report the case of a 31-year-old woman with a 10-year history of discoid lupus, now presenting with dyspnea and pleuritic chest pain of 1 month's duration. A significant drop in hemoglobin and hematocrit levels was observed in association with leukopenia, lymphopenia, a positive ANA, and hypocomplementemia. Chest radiography and computed tomography revealed bilateral infiltrates. An open lung biopsy confirmed the presence of intra-alveolar hemorrhage. Based on the results of the tests and analyses detailed herein, a diagnosis of pulmonary hemorrhage secondary to systemic lupus erythematosus was made. To our knowledge, pulmonary hemorrhage as the initial manifestation of the systemic involvement of discoid lupus has not been reported before.

Euforia-induced acute hepatitis in a patient with scleroderma.

Euforia, a supplement containing a variety of natural ingredients, is widely used as an antioxidant and anti-inflammatory formula. It is not approved by the US Food and Drug Administration and its side effects are unknown. We report a 45-year-old woman with limited systemic sclerosis who presented with jaundice and marked elevation of serum transaminases. One month before, she started taking Euforia juice. A liver biopsy disclosed submassive hepatocellular necrosis with histopathological changes consistent with toxic hepatitis. The patient's symptoms resolved with cessation of Euforia. Six months later, she persisted with abnormal liver function tests, but these resolved 18 months after discontinuation of Euforia. The mechanism by which Euforia causes liver injury is unknown. Some ingredients contained in this supplement (green tea, Aloe vera, noni and goji) are linked to hepatic injury. To our knowledge, this is the first report of hepatotoxicity associated with Euforia.

Tumor ovárico virilizante mixto de células de Sertoli-Leydig/granulosa (ginandroblastoma) en adolescente de 15 años / Virilizing mixed Sertoli-Leydig/ granulosa cell (gynandroblastoma) ovarian tumor in a 15-year-old girl

Los tumores de Sertoli-Leydig constituyen menos del 5% de los tumores ováricos. Presentamos el caso de una adolescente de 15 años de edad, con un cuadro de virilización, amenorrea y dolor abdominal, que fue diagnosticada de tumoración anexial izquierda. En el estudio analítico destacaba una elevación aislada de testosterona. Debido a la integridad de la cápsula, ser unilateral y los deseos de fertilidad de la paciente, se practicó una anexectomía izquierda. El estudio histológico reveló un tumor mixto de células de Sertoli-Leydig/células de la granulosa juvenil con componente heterólogo cartilaginoso, que podría ser considerado como ginandroblastoma. El cuadro de virilización mejoró progresivamente

Sertoli-Leydig cell tumors constitute less than 5% of ovarian tumors. We report the case of a 15-year-old girl with virilization, amenorrhea, and abdominal pain, who was diagnosed with a left annexal tumor. Laboratory investigations revealed isolated testosterone elevation. Because the tumor was unilateral, the capsule was intact, and the patient wished to preserve her fertility, left salpingo-oophorectomy was performed. Histopathological examination revealed a mixed Sertoli-Leydig/juvenile granulosa cell tumor with a cartilaginous heterologous component, which could be considered a gynandroblastoma. Symptoms of virilization progressively improved