cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.

Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation.

Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that upregulation of MMP activity during anti-angiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho=-0.38; **P=0.003), we show that VEGF-blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***P<0.0001). Our data propose a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy.

Efficacy of a single dose of antenatal steroid in surfactant-treated babies under 31 weeks' gestation.

OBJECTIVES: Antenatal steroids in labor improve the outcome in preterm babies. The objective in this retrospective study was to compare the efficacy of one dose of antenatal steroid against the standard course in surfactant-treated babies. METHODS: A total of 226 babies treated with prophylactic surfactant and under 31 weeks' gestation were divided into three groups: group 1 (n = 89), no antenatal steroids; group 2 (n = 68), one dose of antenatal steroids 4-24 h before delivery; and group 3 (n = 69), two or more doses of antenatal steroids 24 h to 7 days before delivery. The three groups were compared for early clinical well-being and ultimate clinical outcome. RESULTS: Apgar and Clinical risk index for babies (CRIB) scores in groups 2 and 3 were similar and both were significantly better than in group 1. Group 2 babies had a 23.5% reduction in serious intraventricular hemorrhage (IVH) (p < 0.0001, relative risk (RR) 0.2 (95% CI 0.07-0.54), numbers needed to treat (NNT) 4.6) and a 22.9% reduction in death (p < 0.001, RR 0.28 (95% CI 0.12-0.63), NNT 4.4) and group 3 babies had a 21.1% reduction in IVH (p < 0.001, RR 0.25 (95% CI 0.10-0.62), NNT 4.6) and a 24.2% reduction in death (p < 0.001, RR 0.23 (95% CI 0.10-0.57), NNT 4.2) compared to group 1. For these parameters, there was no significant difference between groups 2 and 3. CONCLUSIONS: One dose of antenatal steroids given 4-24 h before delivery was clinically comparable to the recommended schedule of the National Institutes of Health in surfactant-treated preterm infants. Should the findings of this study be confirmed in randomized controlled trials, the dosage regimen could be simplified, steroid administration reduced and the interval from delivery reduced in acute clinical conditions.

Effect of thermal treatment on heating characteristics of Ni-Cu alloy for hyperthermia: preliminary studies.

Ferromagnetic Ni-Cu alloy wires were characterized in order to obtain well-defined thermoseeds for application in interstitial hyperthermia of prostate cancer. Thermoseeds have been produced which possess Curie points in the therapeutic hyperthermia range, approximately 40 to 50 degrees C. The effect of thermal treatment and composition on the heating characteristics of the thermoseeds were investigated. The preliminary study shows that the recrystallization is crucial for altering thermoseeds' heating characteristics. Obtaining thermoseeds which behave as desired depends on changes in annealing times and temperatures. One may increase the maximum heating temperature (similar to Curie temperature) by increasing the annealing time and cooling time. Decreasing the lower annealing plateau temperature also increases the maximum seed heating temperature. Higher nickel content compositions did not affect rise time but increased the maximum heating temperature.

Demystifying hypoglycemia. When is it real and how can you tell?

Contrary to popular belief, hypoglycemia is an infrequently encountered condition and its presence is questionable until confirmed by appropriate tests. In ambulatory patients, blood glucose levels obtained during intake of a normal diet are more reliable than those obtained during a glucose tolerance test. If the blood glucose is actually abnormally low and the other two criteria of hypoglycemia are also satisfied, a search for the cause is in order. In hospitalized patients, excessive doses of insulin or oral hypoglycemic agents, the effect of drugs, or chronic renal failure are the most common causes of hypoglycemia. If these factors are absent, another chronic illness known to cause hypoglycemia may be the source. If the cause is still obscure, a thorough evaluation of the endocrine status is warranted.

The idiopathic hypereosinophilic syndrome.

A 14 year old girl with idiopathic hypereosinophilic syndrome is described. In addition to weight loss, anaemia, amenorrhoea, general lethargy, anorexia, mouth ulcers, blisters of hands and feet, and petechial skin rash, she had features of involvement of the cardiovascular system as the major complication. She responded well to treatment. After a comprehensive search of the published reports 18 cases of this syndrome were identified in children under 16 years. Fifteen of these children had involvement of the cardiovascular system as the major source of their morbidity and mortality. Summary of the clinical details and laboratory, biopsy, and necropsy findings of the involvement of the various organ systems of the 18 children is presented.