Background and Aims: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. Methods and Results: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hopsital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (x 2 = 3.99, p = 0.046) and third week (x 2 = 6.53, p = 0.01), although it could not explain tachycardia during follow up. Conclusions: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.

Objectives: To examine knowledge of chronic kidney disease in the general public.Design: Cross-sectional telephone survey.Setting: Hong Kong.Participants: Community-dwelling adults who spoke Chinese in Hong Kong. Results:The response rate was 47.3% (516/1091) out of all subjects who were eligible to participate. The final survey population included 516 adults (55.6% female), of whom over 80% had received a secondary level of education or higher. Close to 20% of the participants self-reported a diagnosis of hypertension. Few (17.8%) realised the asymptomatic nature of chronic kidney disease. Less than half of these individuals identified hypertension (43.8%) or diabetes (44.0%) as risk factors of kidney disease. Awareness of high dietary sodium as a risk factor for chronic kidney disease was high (79.5%).

Nematodes parasitize an alarming number of people and agricultural animals globally and cause debilitating morbidity and mortality. Anthelmintics have been the primary tools used to control parasitic nematodes for the past several decades, but drug resistance is becoming a major obstacle. Xenobiotic detoxification pathways defend against drugs and other foreign chemicals in diverse organisms, and evidence is accumulating that they play a role in mediating resistance to anthelmintics in nematodes. Related anti-oxidation pathways may also provide filarial parasites protection against host free radical-mediated immune responses. Upstream regulatory pathways have received almost no attention in nematode parasites despite their potential to co-regulate multiple detoxification and anti-oxidation genes. The NRF2 transcription factor mediates inducible detoxification and anti-oxidation defenses in mammals and recent studies have demonstrated that it promotes multidrug resistance in some human tumors. Recent studies in the free-living model nematode Caenorhabditis elegans have defined the homologous transcription factor SKN-1 as a master regulator of detoxification and anti-oxidation genes. Despite similar functions, SKN-1 and NRF2 have important differences in structure and regulatory pathways. Protein alignment and phylogenetic analyses indicate that these differences are shared among many nematodes making SKN-1 a candidate for specifically targeting nematode detoxification and anti-oxidation.

High-throughput screening (HTS) is a powerful approach to drug discovery, but many lead compounds are found to be unsuitable for use in vivo after initial screening. Screening in small animals like C. elegans can help avoid these problems, but this system has been limited to screens with low-throughput or no specific molecular target. We report the first in vivo 1536-well plate assay for a specific genetic pathway in C. elegans. Our assay measures induction of a gene regulated by SKN-1, a master regulator of detoxification genes. SKN-1 inhibitors will be used to study and potentially reverse multidrug resistance in parasitic nematodes. Screens of two small commercial libraries and the full Molecular Libraries Small Molecule Repository (MLSMR) of ∼364,000 compounds validate our platform for ultra HTS. Our platform overcomes current limitations of many whole-animal screens and can be widely adopted for other inducible genetic pathways in nematodes and humans.

High-throughput screening (HTS) is a powerful approach for identifying chemical modulators of biological processes. However, many compounds identified in screens using cell culture models are often found to be toxic or pharmacologically inactive in vivo [1][2] . Screening in whole animal models can help avoid these pitfalls and streamline the path to drug development.C. elegans is a multicellular model organism well suited for HTS. It is small (<1 mm) and can be economically cultured and dispensed in liquids. C. elegans is also one of the most experimentally tractable animal models permitting rapid and detailed identification of drug mode-of-action 3 .We describe a protocol for culturing and dispensing fluorescent strains of C. elegans for high-throughput screening of chemical libraries or detection of environmental contaminants that alter the expression of a specific gene. Large numbers of developmentally synchronized worms are grown in liquid culture, harvested, washed, and suspended at a defined density. Worms are then added to black, flat-bottomed 384-well plates using a peristaltic liquid dispenser. Small molecules from a chemical library or test samples (e.g., water, food, or soil) can be added to wells with worms. In vivo, real-time fluorescence intensity is measured with a fluorescence microplate reader. This method can be adapted to any inducible gene in C. elegans for which a suitable reporter is available. Many inducible stress and developmental transcriptional pathways are well defined in C. elegans and GFP transgenic reporter strains already exist for many of them 4 . When combined with the appropriate transgenic reporters, our method can be used to screen for pathway modulators or to develop robust biosensor assays for environmental contaminants.We demonstrate our C. elegans culture and dispensing protocol with an HTS assay we developed to monitor the C. elegans cap 'n' collar transcription factor SKN-1. SKN-1 and its mammalian homologue Nrf2 activate cytoprotective genes during oxidative and xenobiotic stress 5-10 . Nrf2 protects mammals from numerous age-related disorders such as cancer, neurodegeneration, and chronic inflammation and has become a major chemotherapeutic target 11-13 .Our assay is based on a GFP transgenic reporter for the SKN-1 target gene gst-4 14 , which encodes a glutathione-s transferase 6 . The gst-4 reporter is also a biosensor for xenobiotic and oxidative chemicals that activate SKN-1 and can be used to detect low levels of contaminants such as acrylamide and methyl-mercury [15][16] . Video LinkThe 1. Add 5 ml of saturated E. coli OP50 bacterial culture to 500 ml Terrific broth supplemented with 50 μg/ml streptomycin and grow in a shaking incubator (225 rpm) overnight at 37°C.2. Split the overnight bacterial culture into ten 50 ml tubes and centrifuge bacteria in a refrigerated centrifuge at 2,500 rcf for 20 minutes. 3. Decant off LB broth and resuspend each bacterial pellet in 10 ml of liquid nematode growth media (NGM). Shake horizontally in a floor shaker for 15...

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BackgroundDelayed cerebral infarction (DCI) is a major cause of morbidities after aneurysmal subarachnoid hemorrhage (SAH) and typically starts at day 4 to 7 after initial hemorrhage. MicroRNAs (miRNAs) play an important role in posttranscriptional gene expression control, and distinctive patterns of circulating miRNA changes have been identified for some diseases. We aimed to investigate miRNAs that characterize SAH patients with DCI compared with those without DCI.Methods and ResultsCirculating miRNAs were collected on day 7 after SAH in healthy, SAH‐free controls (n=20), SAH patients with DCI (n=20), and SAH patients without DCI (n=20). We used the LASSO (least absolute shrinkage and selection operator) method of regression analysis to characterize miRNAs associated with SAH patients with DCI compared with those without DCI. In the 28 dysregulated miRNAs associated with DCI and SAH, we found that a combination of 4 miRNAs (miR‐4532, miR‐4463, miR‐1290, and miR‐4793) could differentiate SAH patients with DCI from those without DCI with an area under the curve of 100% (95% CI 1.000–1.000, P<0.001). This 4‐miRNA combination could also distinguish SAH patients with or without DCI from healthy controls with areas under the curve of 99.3% (95% CI 0.977–1.000, P<0.001) and 82.0% (95% CI 0.685–0.955, P<0.001), respectively.ConclusionsWe found a 4‐miRNA combination that characterized SAH patients with DCI. The findings could guide future mechanistic study to develop therapeutic targets.

We will prove a result concerning the inclusion of non-trivial invariant ideals inside non-trivial ideals of a twisted crossed product. We will also give results concerning the primeness and simplicity of crossed products of twisted actions of locally compact groups on C * -algebras. Mathematics Subject Classification (2000): 46L05, 46L55The motivation of this study is our recent research on C * -unique groups in [10]. In fact, one interesting question is when the semi-direct product of a C * -unique group with another group is again C * -unique. This turns out to be related to the following question: Given a C * -dynamical system (A, G, α), under what condition will it be true that any non-zero ideal of A × α G contains a non-zeroα-invariant ideal (α being the dual coaction)? The aim of this paper is to study this question.In fact, in the case of discrete amenable groups acting on compact spaces, Kawamura and Tomiyama gave (in [9]) a complete solution of the above question. In [1], Archbold and Spielberg generalised the main result in [9] to the case of discrete C * -dynamical system. In this article, we are going to present a weaker result but in the case of general locally compact groups. As a corollary, we obtain some equivalent conditions for the primeness of crossed products (in terms of the actions). Moreover, we will also give a brief discussion on the simplicity of crossed products (which is related but does not need the main theorem).