Estrogen Receptor-beta Affects the Prognosis of Human Malignant Mesothelioma

Malignant pleural mesothelioma is an asbestos-related neoplasm with poor prognosis, refractory to current therapies, the incidence of which is expected to increase in the next decades. Female gender was identified as a positive prognostic factor among other clinical and biological prognostic markers for malignant mesothelioma, yet a role of estrogen receptors (ERs) has not been studied. Our goal was to investigate ERs expression in malignant mesothelioma and to assess whether their expression correlates with prognosis. Immunohistochemical analysis revealed intense nuclear ER beta staining in normal pleura that was reduced in tumor tissues. Conversely, neither tumors nor normal pleura stained positive for ER alpha. Multivariate analysis of 78 malignant mesothelioma patients with pathologic stage, histologic type, therapy, sex, and age at diagnosis indicated that FRO expression is an independent prognostic factor of better survival. Moreover, studies in vitro confirmed that treatment with 17 beta-estradiol led to an ER beta-mediated inhibition of malignant mesothelioma cell proliferation as well as p21(CIP1) and p27(KIP1) up-regulation. Consistently cell growth was suppressed by ER beta overexpression, causing a G(2)-M-phase cell cycle arrest, paralleled by cyclin B1 and survivin down-regulation. Our data support the notion that ER beta acting as a tumor suppressor is of high potential relevance to prediction of disease progression and to therapeutic response of malignant mesothelioma patients. [Cancer Res 2009;69(11):4598-604]

Cache-Integrated Network Interfaces: Flexible On-Chip Communication and Synchronization for Large-Scale CMPs

Per-core scratchpad memories (or local stores) allow direct inter-core communication, with latency and energy advantages over coherent cache-based communication, especially as CMP architectures become more distributed. We have designed cache-integrated network interfaces, appropriate for scalable multicores, that combine the best of two worlds – the flexibility of caches and the efficiency of scratchpad memories: on-chip SRAM is configurably shared among caching, scratchpad, and virtualized network interface (NI) functions. This paper presents our architecture, which provides local and remote scratchpad access, to either individual words or multiword blocks through RDMA copy. Furthermore, we introduce event responses, as a technique that enables software configurable communication and synchronization primitives. We present three event response mechanisms that expose NI functionality to software, for multiword transfer initiation, completion notifications for software selected sets of arbitrary size transfers, and multi-party synchronization queues. We implemented these mechanisms in a four-core FPGA prototype, and measure the logic overhead over a cache-only design for basic NI functionality to be less than 20%. We also evaluate the on-chip communication performance on the prototype, as well as the performance of synchronization functions with simulation of CMPs with up to 128 cores. We demonstrate efficient synchronization, low-overhead communication, and amortized-overhead bulk transfers, which allow parallelization gains for fine-grain tasks, and efficient exploitation of the hardware bandwidth.

Use of the impedance cardiogram in public access defibrillators as an indicator of cardiopulmonary resuscitation effectiveness

An algorithm has been developed for a Public Access Defibrillator which utilizes distinctive features from the impedance cardiogram (ICG) recorded via defibrillator pads to advise both lay users and minimally trained bystanders to ensure CPR effectiveness. Following ethical approval, data were collected and marked. CPR was administered by trained personnel. 211 cases were gathered and the training set included 106 cases. A retrospective analysis was carried out of simultaneously recorded ECG and ICG. The speed of compressions was calculated by counting the outstanding waves in the ICG during CPR. Also if the base-to-peak amplitude of the ICG is greater than a minimum threshold, the corresponding compressions were classified as being applied with adequate force. For the validation set, adequate speed was detected with 91.45% sensitivity and 96.27% specificity (79826s) and adequate force with 99.94% sensitivity and 97.91% specificity (91973s). © 2011 CCAL.

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants.

Oxidative and endoplasmic reticulum stresses mediate apoptosis induced by modified LDL in human retinal Müller cells

We previously showed that extravasated, modified LDL is implicated in pericyte loss in diabetic retinopathy (DR). Here, we investigate whether modified LDL induces apoptosis in retinal Müller glial cells.

Peer effects in UK adolescent substance use: Never mind the classmates?

This article estimates peer influences on the alcohol, tobacco and cannabis use of UK adolescents. We present evidence of large, positive and statistically significant peer effects in all three behaviours when classmates are taken as the reference group. We also find large, positive and statistically significant associations between own substance use and friends' substance use. When both reference groups are considered simultaneously, the influence of classmates either disappears or is much reduced, whereas the association between own and friends' behaviours does not change. The suggestion is that classmate behaviour is primarily relevant only inasmuch as it proxies for friends' behaviour.

Matrilysin-1 mediates bronchiolization of alveoli, a potential premalignant change in lung cancer

Matrilysin-1 (also called matrix metalloproteinase-7) is expressed in injured lung and in cancer but not in normal epithelia. Bronchiolization of the alveoli (BOA), a potential precursor of lung cancer, is a histologically distinct type of metaplasia that is composed of cells resembling airway epithelium in the alveolar compartment. We demonstrate that there is increased expression of matrilysin-1 in human lesions and BOA in the CC10-human achaete-scute homolog-1 transgenic mouse model. Forced expression of the matrilysin-1 gene in immortalized human normal airway epithelial BEAS-2B and HPLD1 cells, which do not normally express matrilysin-1, promoted cellular migration, suggesting a functional link for BOA formation via bronchiolar cell migration. In addition, matrilysin-1 stimulated proliferation and inhibited Fas-induced apoptosis, while a knockdown by RNA interference decreased cell growth, migration, and increased sensitivity to apoptosis. Western blotting demonstrated increased levels of phospho-p38 and phospho-Erk1/2 kinases after matrilysin-1 expression. Gene expression analysis uncovered several genes that were related to cell growth, migration/movement, and death, which could potentially facilitate bronchiolization. In vivo, the formation of BOA lesions was reduced when CC10-human achaete-scute homolog-1 mice were crossed with matrilysin-1 null mice and was correlated with reduced matrilysin-1 expression in BOA. We conclude that matrilysin-1 may play an important role in the bronchiolization of alveoli by promoting proliferation, migration, and attenuation of apoptosis involving multiple genes in the MAP kinase pathway.