Macromolecular crystallography beamline X25 at the NSLS.

Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community.

Clostridium difficile-associated disease acquired in the cardiothoracic intensive care unit.

OBJECTIVES: To determine the prevalence, severity, and outcome associated with Clostridium difficile-associated disease (CDAD) acquired while in the cardiothoracic intensive care unit (CTICU). DESIGN: A 5-year retrospective study. SETTING: The CTICU. PARTICIPANTS: All CTICU patients with a positive C difficile stool toxin assay 48 hours after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The results of all CTICU patients with a positive C difficile stool toxin assay were obtained from the Microbiology Department. Each patient's medical notes and charts then were reviewed in turn. A total of 27 of 5,199 (0.5%) CTICU patients acquired CDAD. The median age was 74 years (IQR 68-77), and 17 (63%) patients were male. There were 21 (78%) surgical patients; 13 (62%) were elective admissions. The most frequent diagnosis on admission was valvular heart disease (10 [37%] patients). Sixteen (59%) patients underwent coronary artery bypass graft (CABG) surgery and/or valvular heart surgery. The median interval between CTICU admission and CDAD diagnosis was 10 days (IQR 5-18). Previously identified risk factors for ICU-acquired CDAD included age >65 years (23), antibiotic use (26), and medical device requirements (27). At the time of diagnosis, 14 (52%) patients had moderate CDAD. After treatment initiation, 8 (30%) patients developed worsening CDAD. The 30-day in-hospital mortality rate for CTICU-acquired CDAD was 26% (7 patients). CONCLUSIONS: C difficile-associated disease rarely is acquired in the CTICU. Approximately one third of patients may experience disease progression, and just over a quarter may die within 30 days of diagnosis. The implementation of recommended severity definitions and treatment algorithms may reduce complication rates and merits prospective evaluation.

A study of muscle tissue oxygenation and peripheral microcirculatory dysfunction in cirrhosis using near infrared spectroscopy.

BACKGROUND: The circulatory dysfunction associated with cirrhosis is well described. Reduced systemic vascular resistance and high cardiac output are the main features of the hyperdynamic state, but involvement of the peripheral microcirculation in this process is poorly understood. Near infrared spectroscopy (NIRS) has been used to assess muscle tissue oxygenation (StO(2)) in haemorrhagic and septic shock. Vascular occlusion testing (VOT) can produce dynamic changes in StO(2) which represent tissue oxygen extraction, delivery, and hence, surrogate markers of microvascular function. AIMS: We aimed to investigate dynamic StO(2) changes in the peripheral microcirculation of patients with cirrhosis. METHODS: Thirty-five subjects were examined (25 cirrhosis, 10 healthy volunteers) with an InSpectra 650 StO(2) monitor and 15 mm thenar probe. Brachial VOT was applied at systolic blood pressure +50 mmHg for 3 min, in triplicate. Dynamic StO(2) parameters are reported for baseline, downslope, upslope, area over ischaemic curve, overshoot, area under recovery curve and recovery time. RESULTS: Patients with cirrhosis demonstrated significantly larger post-occlusive hyperaemic variables compared with volunteers: overshoot (17 vs 15%, P=0.009), area under recovery curve (25.1 vs 16.3 %/min, P<0.001) and recovery time (3.0 vs 2.2 min, P<0.001). Magnitude of change was also seen to increase with disease stage as defined by Child-Pugh score. Serial VOT revealed microcirculatory ischaemic adaptation in volunteers, which was absent in cirrhosis. CONCLUSIONS: NIRS can identify dynamic changes in muscle tissue oxygenation in cirrhosis which are compatible with microcirculatory vasodilatation. Ischaemic adaptation was seen in controls but not in patients with cirrhosis. NIRS techniques offer a novel approach to the assessment of peripheral vascular dysfunction in cirrhosis.

Comment on Metabolomics for a Millenniums-Old Crop: Tea Plant (Camellia sinensis).

Metabolomics is the study of metabolite profiles at the system level. Since its introduction in the early 2000s, metabolomics has greatly contributed to the understanding of the distribution of metabolites in organisms under various physiological conditions. In this comment, we show our research on the temporal development of metabolomics in general and in agricultural, food, and nutritional sciences. According to our investigation, metabolomics develops in a sigmoid kinetics. On the basis of the analysis, we made a prediction on the future of the metabolomics study, which may benefit the research community in the field.

Epigenetics for the 21st-Century Biology Student.

Epigenetics, a rapidly emerging biological science, investigates changes in gene expression without any change to the primary DNA sequence. Epigenetics plays an important role in diverse areas, including nutritional sciences, psychology, and environmental sciences. In addition, epigenetic phenomena are closely implicated in various diseases, including cancer and neurological disorders. Even though the importance of epigenetics has been widely discussed in the literature, there is no quantitative assessment on the development of epigenetics. In this paper, we show our metadata analysis of PubMed to quantitatively measure the temporal development of epigenetics. Our analysis indicates that the publication volume of epigenetics will reach 20.7% of all genetics paper in 10 years (year 2029). Based on our analysis, we suggest that epigenetics be added to the biology undergraduate curriculum.

Proteomics: advances in biomarker discovery.

The challenges encountered by proteomic researchers seeking diagnostic, prognostic and mechanistic markers were the subject of the 1-day meeting, Proteomics: Advances in Biomarker Discovery hosted by EuroSciCon. The speakers had a broad range of clinical and basic science interests, and presented data using a number of proteomic platforms to search for discriminant biomarkers of disease in easily accessible bodily fluids including serum and urine. Several potential pitfalls for proteomic researchers were mentioned and the potential of collaborative networks between research institutions to increase the size and power of clinical studies was discussed. Overall, the meeting highlighted the exciting opportunities that proteomic techniques offer for discovering not only diagnostic but also prognostic and mechanistic markers of a number of clinically important diseases.

Chronic liver disease--an increasing problem: a study of hospital admission and mortality rates in England, 1979-2005, with particular reference to alcoholic liver disease.

AIMS: To determine time trends in hospital admissions for chronic liver disease in England between 1989/1990 and 2002/2003, mortality rates in England and Wales between 1979 and 2005, and the influence of alcohol-related disease on these trends. METHODS: Hospital episode statistics for admissions in England were obtained from the Information Center for Health and Social Care and mortality data for England and Wales from the Office for National Statistics. RESULTS: Hospital admission rates for chronic liver disease increased by 71% in males and 43% in females over the study period. This increase was largely due to alcoholic liver disease, admission rates for which more than doubled between 1989/1990 and 2002/2003. While there was a smaller rise for chronic viral hepatitis B and C, admission rates declined for hepatitis A, autoimmune hepatitis, and primary biliary cirrhosis. Mortality rates for chronic liver disease more than doubled between 1979 and 2005. Two thirds of these deaths were attributable to alcohol-related liver disease in 2005. The highest rate of alcoholic liver disease mortality was in the 45-64 age group, and the largest percentage increase between 1979 and 2005 occurred in the 25-34 age group. CONCLUSIONS: Hospital admissions and mortality in England from chronic liver disease are increasing. The underlying reasons are complex, but alcohol-induced liver disease makes a major contribution. There are clear social and health implications if the trend continues and addressing alcohol-related liver disease should be a public health priority.

Evaluation of mass spectrometry of urinary proteins and peptides as biomarkers for cats at risk of developing azotemia.

OBJECTIVE: To evaluate proteomic delineation of feline urine by mass spectrometry as a method for identifying biomarkers in cats at risk of developing azotemia. SAMPLES: Urine samples from geriatric cats (> 9 years old) with chronic kidney disease and nonazotemic cats that either remained nonazotemic (n = 10) or developed azotemia (10) within 1 year. PROCEDURES: Optimization studies with pooled urine were performed to facilitate the use of surface enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for analysis of the urinary proteome of cats. Urine samples from nonazotemic cats at entry to the study were analyzed via SELDI-TOF-MS with weak cation exchange and strong anion exchange arrays. Spectral data were compared to identify biomarkers for development of azotemia. RESULTS: Low protein concentration in feline urine precluded direct application to array surfaces, and a buffer exchange and concentration step was required prior to SELDI-TOF-MS analysis. Three preparation conditions by use of weak cation and strong anion exchange arrays were selected on the basis of optimization studies for detection of biomarkers. Eight potential biomarkers with an m/z of 2,822, 9,886, 10,033, 10,151, 10,234, 11,653, 4,421, and 9,505 were delineated. CONCLUSIONS AND CLINICAL RELEVANCE: SELDI-TOF-MS can be used to detect urinary low-molecular weight peptides and proteins that may represent biomarkers for early detection of renal damage. Further study is required to purify and identify potential biomarkers before their use in a clinical setting.

Proteomic approaches in the search for biomarkers of liver fibrosis.

Chronic liver diseases (CLDs) can cause progressive hepatic fibrosis culminating in cirrhosis. Fibrosis staging requires liver biopsy, which is invasive, expensive and frequently poorly tolerated by patients. Serum-based panels of fibrosis biomarkers have been developed as alternatives to biopsy. Recent advances in high-throughput proteomic methods have the potential to optimise combinations of biomarkers for the diagnosis of liver fibrosis. Here, we review the key recent developments in the field of proteomics and their application to this important clinical question. We critically discuss the challenges and priorities for future research that are of critical importance to clinical hepatology.

Treatment of hepatitis C virus infection in intravenous drug users.

BACKGROUND: Hepatitis C virus (HCV) infection is common among intravenous drug users, and because of the long latent period, HCV liver disease is set to increase. OBJECTIVES: We sought to examine practice guidelines regarding treatment of HCV in drug users and to review the evidence for current practices. METHODS: A structured search of the Pubmed database, websites of the National Institute for Clinical Excellence and national and international expert groups and opinion of independent experts in the field. RESULTS AND CONCLUSIONS: All those infected with HCV need to be assessed to ascertain whether they have active ongoing viral replication and the extent of liver damage. HCV-infected individuals should be educated about the modes of transmission and means of reducing the risk of infecting others. They should also be advised to avoid cofactors (especially alcohol) that accelerate the progression of liver disease. Specific treatment with antivirals can cause viral clearance and prevent the progression of liver disease. Therapy is effective in those on opiate-replacement treatments and also in motivated individuals who continue to use intravenous drugs. The decision whether to treat drug users should be made jointly by specialists in the management of viral hepatitis and addiction on a case-by-case basis. Current combination drug regimens are expensive but are claimed to be cost-effective, and are certainly much less costly than managing end-stage liver disease. In addition to satisfactory sustained viral response rates, other benefits such as a beneficial effect on drug habit, self-esteem and rehabilitation have been reported. Encouraging suitable drug users to take-up and comply with treatment seems to be more easily achieved in supportive drug dependency unit settings (rather than the more formal surroundings of a hospital clinic).