Metabolomics: Basic Principles and Strategies

Metabolomics is the study of metabolome within cells, biofluids, tissues, or organisms to comprehensively identify and quantify all endogenous and exogenous low-molecular-weight (<1 kDa) small molecules/metabolites in a biological system in a high-throughput manner. Metabolomics has several applications in health and disease including precision/personalized medicine, single cell, epidemiologic population studies, metabolic phenotyping, and metabolome-wide association studies (MWAS), precision metabolomics, and in combination with other omics disciplines as integrative omics, biotechnology, and bioengineering. Mass spectrometry (MS)-based metabolomics/lipidomics provides a useful approach for both identification of disease-related metabolites in biofluids or tissue and also encompasses classification and/or characterization of disease or treatment-associated molecular patterns generated from metabolites. Here, in this review, we provide a brief overview of the current status of promising MS-based metabolomics strategies and their emerging roles, as well as possible challenges

Role of liver biopsy in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease

Choosing Sensor Configuration for a Flexible Structure Using Full Control Synthesis

Optimal locations and types for feedback sensors which meet design constraints and control requirements are difficult to determine. This paper introduces an approach to choosing a sensor configuration based on Full Control synthesis. A globally optimal Full Control compensator is computed for each member of a set of sensor configurations which are feasible for the plant. The sensor configuration associated with the Full Control system achieving the best closed-loop performance is chosen for feedback measurements to an output feedback controller. A flexible structure is used as an example to demonstrate this procedure. Experimental results show sensor configurations chosen to optimize the Full Control performance are effective for output feedback controllers

Intermittent Inflammatory Bowel Disease and Microscopic Colitis: Variant or Epiphenomenon?

Background: Idiopathic inflammatory bowel disease and microscopic colitis are distinct entities; however, some clinical features overlap. Aims: To identify if these alternative diagnoses may direct clinical therapy more effectively.Methods: We describe seven patients who had intermittent phases of either inflammatory bowel disease or microscopic colitis in at least two separate occasions with matching clinical and endoscopic pictures. Results: Diarrhea was the presenting symptom in all cases. In two of seven cases, the initial diagnosis was microscopic colitis, and in five cases it was inflammatory bowel disease. Addition of medication specific to diagnosis had resulted in improvement in six out of seven cases. Among the seven patients we reported, three had used nonsteroidal antiinflammatory drugs, a well-known trigger, before the onset of microscopic colitis. Conclusions: Inflammatory bowel disease and microscopic colitis are distinct clinicopathologic entities that may coexist in the same patient. Triggering factors for microscopic colitis in the general population can also be the culprit in inflammatory bowel disease patients. Microscopic colitis may present as an epiphenomenon which is superimposed on predisposing inflammatory bowel disease patients. A thorough synthesis of all clinical, medication, endoscopic, radiology, and pathological data is crucial in these patients

Klikkien ja ihanteiden välissä. Helsingin Sanomien esimiestoimittajien ammatti-ideologia ja analytiikan käyttö arjen työssä

Tutkielma tarkastelee, millaiseksi sanomalehden esimiestoimittajien ammatti-ideologia muodostuu tilanteessa, jossa toimituksessa on yhä enemmän tietoa lukijoiden kiinnostuksesta juttuja kohtaan. Se tutkii kahta ammatti-ideologiaan perinteisesti kuulunutta ihannetta: autonomiaa ja julkisen palvelun tehtävää. Tarkoituksena on selvittää esimiestoimittajien käsityksiä yleisösuhteesta ja siitä, millaisessa roolissa heidän mielestään yhteiskunnallisesti merkittävien uutisten tulisi olla journalismissa. Ihanteiden ilmenemistä tarkastellaan analytiikan eli lukijamäärien ja lukuaikojen seuraamiseen liittyen. Tutkimuksellisena viitekehyksenä on erityisesti ajatus toimittajien ammatti-ideologian muuttumisesta journalismin siirtyessä korkean modernin vaiheesta notkeaan moderniin. Aineisto on koottu 14 Helsingin Sanomien väliportaan esimiehenä työskentelevän toimittajan teemahaastatteluilla. Tutkielmassa on haastateltu yhtä lukuun ottamatta kaikki lehden uutisosastojen esimiehet sekä suurin osa verkon ja paperilehden uutispäälliköistä. Aineiston analyysissä on käytetty teoriaohjaavaa lähestymistapaa, jonka avulla haastatteluista on etsitty korkeaan ja notkeaan moderniin kuuluvia ammatti-ideologian piirteitä. Tulosten mukaan esimiestoimittajat haluavat ottaa huomioon lukijoiden kiinnostuksen ja toiveet niissä päätöksissä, joita he tekevät työssään. Korkeaan moderniin kuulunut etäinen yleisösuhde on muuttunut ihmisläheisemmäksi. Tämä vaikuttaa sekä ihanteisiin että suoraan arjen työhön. Viime kädessä päätösvallan valinnoista esimiestoimittajat haluavat silti pitää toimituksella eikä yleisöllä. Ajatus julkisen palvelun tehtävästä on pysynyt enemmän korkean modernin kaltaisena. Esimiestoimittajat uskovat, että lehden tärkeä tarkoitus on yhä kertoa yhteiskunnallisesti merkittävistä asioista. Myös julkisen palvelun ihanne on kuitenkin saanut piirteitä notkeasta modernista. Juttujen kiinnostavuutta pidetään entistä tärkeämpänä. Lisäksi toimittajien rooli valtarakenteiden haastajina, vallan vahtikoirina, vaikuttaa korostuvan aiemman konsensushakuisen raportoinnin sijaan

A novel, rapidly acquired and persistent spatial memory task that induces immediate early gene expression

<p>Abstract</p> <p>Background</p> <p>The Morris water maze task is a hippocampus-dependent learning and memory test that typically takes between 3 days to 2 weeks of training. This task is used to assess spatial learning and induces the expression of genes known to be crucial to learning and memory in the hippocampus. A major caveat in the protocol is the prolonged duration of training, and difficulty of assessing the time during training in which animals have learned the task. We introduce here a condensed version of the task that like traditional water maze tasks, creates lasting hippocampus-dependent spatial cognitive maps and elicits gene expression following learning.</p> <p>Methods</p> <p>This paradigm was designed for rats to quickly acquire a hippocampus-dependent spatial cognitive map and retain this memory for at least 24 hours. To accomplish this, we interspersed visible and hidden training trials, delivering them in a massed fashion so training takes a maximum of 15 minutes. Learning was assessed based on latencies to the platform during each training trial, as well as time spent in the goal quadrant during probe testing 30 minutes and 24 hours after training. Normal rats were compared to two impaired cohorts (rats with fimbria-fornix lesions and rats administered NMDA receptor antagonist (CPP)). To quantitate hippocampal expression of known learning genes, real-time polymerase chain reaction (RT-PCR) was performed on hippocampal cDNA.</p> <p>Results</p> <p>We show that massed training using alternating visible and hidden training trials generates robust short-term working and long-term reference memories in rats. Like the traditional Morris water maze paradigm, this task requires proper hippocampal function, as rats with fimbria-fornix lesions and rats administered CPP fail to learn the spatial component of the task. Furthermore, training in this paradigm elicits hippocampal expression of genes upregulated following learning in a variety of spatial tasks: <it>homer1a, cfos </it>and <it>zif268</it>.</p> <p>Conclusions</p> <p>We introduce here a condensed version of the Morris water maze, which is like a traditional water maze paradigm, in that it is hippocampus-dependent, and elicits hippocampal expression of learning genes. However, this task is administered in 15 minutes and induces spatial memory for at least 24 hours.</p