Inhaled Corticosteroids Alone and in Combination With Long-Acting beta(2) Receptor Agonists to Treat Reduced Lung Function in Preterm-Born Children A Randomized Clinical Trial:A Randomized Clinical Trial

IMPORTANCE: Decreases in future lung function are a hallmark of preterm birth, but studies for management of decreased lung function are limited. OBJECTIVE: To determine whether 12 weeks of treatment with inhaled corticosteroids (ICS) alone or in combination with long-acting β(2) agonists (LABA) improves spirometry and exercise capacity in school-aged preterm-born children who had percent predicted forced expiratory volume in 1 second (%FEV(1)) less than or equal to 85% compared with inhaled placebo treatment. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, placebo-controlled trial was conducted to evaluate ICS and ICS/LABA against placebo. Preterm-born children (age, 7-12 years; gestation ≤34 weeks at birth) who did not have clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. A total of 144 preterm-born children at the Children’s Hospital for Wales in Cardiff, UK, were identified and enrolled between July 1, 2017, and August 31, 2019. INTERVENTIONS: Each child was randomized to 1 of 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. Children receiving preexisting ICS treatment underwent washout prior to randomization to ICS or ICS/LABA. MAIN OUTCOMES AND MEASURES: The primary outcome was between-group differences assessed by adjusted pretreatment and posttreatment differences of %FEV(1) using analysis of covariance. Intention-to-treat analysis was conducted. RESULTS: Of 144 preterm-born children who were identified with %FEV(1) less than or equal to 85%, 53 were randomized. Treatment allocation was 20 children receiving ICS (including 5 with prerandomization ICS), 19 children receiving ICS/LABA (including 4 with prerandomization ICS), and 14 children receiving placebo. The mean (SD) age of children was 10.8 (1.2) years, and 29 of the randomized children (55%) were female. The posttreatment %FEV(1) was adjusted for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values. Posttreatment adjusted means for %FEV(1), using analysis of covariance, were 7.7% (95% CI, −0.27% to 15.72%; P = .16) higher in the ICS group and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the ICS/LABA group compared with the placebo group. Active treatment decreased the fractional exhaled nitric oxide and improved postexercise bronchodilator response but did not improve exercise capacity. One child developed cough when starting inhaler treatment; no other adverse events reported during the trial could be attributed to the inhaler treatment. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial suggest that combined ICS/LABA treatment is beneficial for prematurity-associated lung disease in children. TRIAL REGISTRATION: EudraCT number: 2015-003712-2

Hubble Space Telescope and Ground-Based Observations of Type Ia Supernovae at Redshift 0.5: Cosmological Implications

We present observations of the Type Ia supernovae (SNe) 1999M, 1999N, 1999Q, 1999S, and 1999U, at redshift z~0.5. They were discovered in early 1999 with the 4.0~m Blanco telescope at Cerro Tololo Inter-American Observatory by the High-z Supernova Search Team (HZT) and subsequently followed with many ground-based telescopes. SNe 1999Q and 1999U were also observed with the Hubble Space Telescope. We computed luminosity distances to the new SNe using two methods, and added them to the high-z Hubble diagram that the HZT has been constructing since 1995. The new distance moduli confirm the results of previous work. At z~0.5, luminosity distances are larger than those expected for an empty universe, implying that a ``Cosmological Constant,'' or another form of ``dark energy,'' has been increasing the expansion rate of the Universe during the last few billion years.Comment: 68 pages, 22 figures. Scheduled for the 01 February 2006 issue of Ap.J. (v637

A Novel Mouse Model of Endometriosis Mimics Human Phenotype and Reveals Insights into the Inflammatory Contribution of Shed Endometrium

Endometriosis is an estrogen-dependent inflammatory disorder characterized by the presence of endometrial tissue outside the uterine cavity. Patients experience chronic pelvic pain and infertility, with the most likely origin of the tissue deposits (lesions) being endometrial fragments shed at menses. Menstruation is an inflammatory process associated with a dramatic increase in inflammatory mediators and tissue-resident immune cells. In the present study, we developed and validated a mouse model of endometriosis using syngeneic menstrual endometrial tissue introduced into the peritoneum of immunocompetent mice. We demonstrate the establishment of endometriotic lesions that exhibit similarities to those recovered from patients undergoing laparoscopy. Specifically, in both cases, lesions had epithelial (cytokeratin+) and stromal (vimentin/CD10+) cell compartments with a well-developed vasculature (CD31+ endothelial cells). Expression of estrogen receptor β was increased in lesions compared with the peritoneum or eutopic endometrium. By performing experiments using mice with green fluorescent protein–labeled macrophages (MacGreen) in reciprocal transfers with wild-type mice, we obtained evidence that macrophages present in the peritoneum and in menses endometrium can contribute to the inflammatory microenvironment of the lesions. In summary, we developed a mouse model of endometriosis that exhibits similarities to human peritoneal lesions with respect to estrogen receptor expression, inflammation, and macrophage infiltration, providing an opportunity for further studies and the possible identification of novel therapies for this perplexing disorder

Radiotherapy exposure directly damages the uterus and causes pregnancy loss

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.</p

The value and opportunities of community-and citizen-based approaches to tropical forest biodiversity monitoring

The biodiversity sourcebook is accessible in pdf format for free from:•GOFC-GOLD Land Cover Office website: http://www.gofcgold.wur.nl/sites/gofcgold-geobon_biodiversitysourcebook.php•GEO BON website:http://geobon.org

Use of quantitative polymerase chain reaction (qPCR) for the diagnosis and monitoring of CNS leukaemia

No abstract available

Hypoxyprobe™ reveals dynamic spatial and temporal changes in hypoxia in a mouse model of endometrial breakdown and repair

BACKGROUND: Menstruation is the culmination of a cascade of events, triggered by the withdrawal of progesterone at the end of the menstrual cycle. Initiation of tissue destruction and endometrial shedding causes spiral arteriole constriction in the functional layer of the endometrium. Upregulation of genes involved in angiogenesis and immune cell recruitment, two processes that are essential to successful repair and remodelling of the endometrium, both thought to be induced by reduced oxygen has been reported. Evidence for stabilisation/increased expression of the transcriptional regulator hypoxia inducible factor in the human endometrium at menses has been published. The current literature debates whether hypoxia plays an essential role during menstrual repair, therefore this study aims to delineate a role for hypoxia using a sensitive detection method (the Hypoxyprobe™) in combination with an established mouse model of endometrial breakdown and repair. RESULTS: Using our mouse model of menses, during which documented breakdown and synchronous repair occurs in a 24 h timeframe, in combination with the Hypoxyprobe™ detection system, oxygen tensions within the uterus were measured. Immunostaining revealed striking spatial and temporal fluctuations in hypoxia during breakdown and showed that the epithelium is also exposed to hypoxic conditions during the repair phase. Furthermore, time-dependent changes in tissue hypoxia correlated with the regulation of mRNAs encoding for the angiogenic genes vascular endothelial growth factor and stromal derived factor (Cxcl12). CONCLUSIONS: Our findings are consistent with a role for focal hypoxia during endometrial breakdown in regulating gene expression during menses. These data have implications for treatment of endometrial pathologies such as heavy menstrual bleeding

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum