Expression profile of oestrogen receptors and oestrogen-related receptors is organ specific and sex dependent: the Japanese medaka Oryzias latipes model.

Gene expression of all known subtypes of oestrogen receptor (ER) and oestrogen-related receptor (ERR) in multiple organs and both sexes of the Japanese medaka Oryzias latipes was profiled and systematically analysed. As revealed by statistical analyses and low-dimensional projections, the expressions of ERRs proved to be organ and sex dependent, which is in contrast with the ubiquitous nature of ERs. Moreover, expressions of specific ERR isoforms (ERRγ1, ERRγ2) were strongly correlated with that of all ERs (ERα, ERß1 and ERß2), suggesting the existence of potential interactions. Findings of this study shed light on the co-regulatory role of particular ERRs in oestrogen-ERs signalling and highlight the potential importance of ERRs in determining organ and sex-specific oestrogen responses. Using O. latipes as an alternative vertebrate model, this study provides new directions that call for collective efforts from the scientific community to unravel the mechanistic action of ER-ERR cross-talks, and their intertwining functions, in a cell and sex-specific manner in vivo.

Draft Genome Sequences of Nine Stenotrophomonas maltophilia Isolates from a Freshwater Catchment Area in Hong Kong.

Stenotrophomonas maltophilia is a widely distributed, Gram-negative bacillus that is increasingly identified as a multidrug-resistant opportunistic pathogen of concern. Here, we report the draft genome sequences of nine strains that were isolated from a freshwater catchment area in Hong Kong, corresponding to four different monophyletic lineages within the species.

Galactic water vapor emission: further observations of variability.

Recent observations of the 1.35-centimeter line emission of water vapor from galactic sources show short-term variability in the spectra of several sources. Two additional sources, Cygnus 1 and NGC 6334N, have been observed, and the spectra of W49 and VY Canis Majoris were measured over a wider range of radial velocity.

Spectra, Variability, Size, and Polarization of H2O Microwave Emission Sources in the Galaxy.

Radio spectral line radiation of water molecules at a wavelength of 1.35 centimeters has been measured from eight sources in the galaxy. The sources are less than I arc minute in diameter, have extremely high brightness temperatures, and show many spectral features. Some spectral features are slightly polarized and some have changed greatly in intensity in a few weeks time.

Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes.

BACKGROUND: Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival. AIM: To evaluate biochemical profiles, liver-related outcomes and adverse events following fenofibrate therapy in PBC patients with incomplete response to ursodeoxycholic acid (UDCA). METHODS: A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates and UDCA (FF) or UDCA alone, adjusted for a propensity score to account for treatment selection bias. RESULTS: A total of 120 patients were included (FF group n = 46, UDCA group n = 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase ≤1.67 times the upper limit of normal] in the FF and UDCA groups, respectively (P = 0.0001). Fenofibrate was also associated with improved decompensation-free and transplant-free survival [hazard ratio (HR) 0.09, 95% CI 0.03-0.32, P = 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR 0.40, 95% CI 0.17-0.93, P = 0.03). Twenty-two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in the FF group (P = 0.005). CONCLUSIONS: Fenofibrate therapy is associated with significant improvement in alkaline phosphatase, decompensation-free and transplant-free survival in PBC patients with incomplete UDCA response. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity of alkaline phosphatase as an appropriate response criteria for fibrate therapy.

Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 1 - history, mechanism, measurements, and pathophysiology.

UNLABELLED: Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. TAKE HOME MESSAGE: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 2. measurement, risk factors, and step-wise approach to treatment.

UNLABELLED: As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 µg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. TAKE HOME MESSAGE: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.

Aortic valve reoperation after homograft or autograft replacement.

BACKGROUND AND AIM OF THE STUDY: With increasing use of homograft and autograft aortic valves for aortic valve replacement (AVR), more patients will be presenting for aortic valve reoperation due to structural degeneration of the homograft or autograft valve. Management options include homograft re-replacement, which may require extensive surgery, versus AVR with a mechanical valve or a stented xenograft. Here, results are reported in 18 consecutive patients who underwent aortic valve re-replacement (AVreR) after previous homograft or autograft insertion. METHODS: Between May 1976 and March 2001, 18 patients underwent AVR after previous homograft (n = 16) or autograft (n = 2) insertion. The homograft or autograft had been implanted as a full root in eight patients (44%), as a mini-root in one (6%), and in the subcoronary position in nine (50%). Indication for the reoperation was structural valve degeneration (n = 14; 72%) in one occasion combined with aneurysm of the homograft, or endocarditis (n = 4; 22%), and seven (39%) presented as a non-elective procedure. The median interval between the two operations was 5.4 years (range: 0.3-10.8 years). RESULTS: Fourteen patients (78%) received either a mechanical valve (n = 12; 67%) or a stented xenograft valve (n = 2; 11%). Four others (22%) required root re-replacement with either another homograft (n = 3) or a mechanical valved conduit (n = 1) for endocarditis (n = 2) or an associated aneurysm (n = 2). Overall hospital mortality was 11% (n = 2) due to stroke (n = 1) or respiratory failure (n = 1). Two patients died 3.1 and 7.0 years after the procedure. CONCLUSION: Aortic valve reoperation after previous homograft or autograft implantation is a rare operation and presents a high-risk group. A simplified approach was preferred by utilizing mechanical or stented xenograft valves at reoperation, while homograft re-replacement was reserved for endocarditis or an associated aneurysm.

Fatal cardiomyopathy after revision total hip replacement for fracture of a ceramic liner.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt-chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy.We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Effectiveness of facemasks to reduce exposure hazards for airborne infections among general populations.

Facemasks are widely used as a protective measure by general public to prevent inhalation of airborne pathogens including seasonal, swine and other forms of influenza and severe acute respiratory syndrome (SARS), etc. However, scientific data on effectiveness of facemasks in reducing infections in the community are extremely limited and even inconsistent. In this work, two manikins labelled as 'source' and 'susceptible' were used to measure the protection provided by facemasks under various emission scenarios. The source was modified to generate polydisperse ultrafine particles, whereas the susceptible was modified to mimic a realistic breathing pattern. The facemask was challenged by both pseudo-steady and highly transient emissions generated by an expiratory process where parameters, such as separation distance between manikins, emission velocity and expiratory duration, were controlled and measured systematically. Performances of four different types of facemask fits, varying from ideal to normal wearing practice, were also investigated. Under the pseudo-steady concentration environment, facemask protection was found to be 45 per cent, while under expiratory emissions, protection varied from 33 to 100 per cent. It was also observed that the separation between the source and the manikin was the most influential parameter affecting facemask protection.

The SARS outbreak in a general hospital in Tianjin, China -- the case of super-spreader.

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a high case-fatality rate and devastating socio-economic impact. In this report we summarized the results from an epidemiological investigation of a SARS outbreak in a hospital in Tianjin, between April and May 2003. We collected epidemiological and clinical data on 111 suspect and probable cases of SARS associated with the outbreak. Transmission chain and outbreak clusters were investigated. The outbreak was single sourced and had eight clusters. All SARS cases in the hospital were traced to a single patient who directly infected 33 people. The patients ranged from 16 to 82 years of age (mean age 38.5 years); 38.7% were men. The overall case fatality in the SARS outbreak was 11.7% (13/111). The outbreak lasted around 4 weeks after the index case was identified. SARS is a highly contagious condition associated with substantial case fatality; an outbreak can result from one patient in a relatively short period. However, stringent public health measures seemed to be effective in breaking the disease transmission chain.