Complication and hysteresis of the self-sustaining motion of a molecular-machine assembly caused by the directionality of the applied light energy

Living organisms show self-sustained motion, make behavioural decisions in response to their environment, and replicate themselves in a genetic manner. Recently, nanometre-sized molecular machines have been assembled to realise macroscopic systems that exhibit self-sustaining dynamics. However, it is unclear how such systems can acquire the ability to make decisions in response to their environment. We have previously reported that the behaviour of a light-driven self-oscillating crystal becomes complicated when the driving light is polarised. Here, we reveal by incorporating a theoretical analysis that the apparent complexity is due to the orientation of the crystal relative to the incident light. An additional reason for this complexity is that the components remember the polarity of the preceding light input. Our results provide a new concept, i.e., collaboration between a motor molecule to achieve self-sustaining motion and a responsive machine for storing information to realise self-governed dynamics in a multimolecular architecture

Geographical location affects the levels and association of trimethylamine N-oxide with heart failure mortality in BIOSTAT-CHF:a post-hoc analysis

No abstract available

Implications of serial measurements of natriuretic peptides in heart failure:insights from BIOSTAT-CHF

Natriuretic peptides [NP, including B-typenatriuretic peptide (BNP) and amino-terminalprohormone of BNP (NT-proBNP)] arethe gold-standard biomarkers in heart failure (HF) management,1 with NP levels atpresentation/admission routinely used fordiagnostic and prognostic purposes. NPlevels at discharge/follow-up also showassociation with outcomes, and NP levelsfollowing HF treatment add further value totailoring risk. However, the usefulness of NPserial measurements beyond conventionalHF treatment in clinical practice still remainsa matter of controversy. A cohort withcurrent HF guideline-based treatment wouldprovide an ideal setting to revisit usefulnessof NP serial measurements in risk stratification of HF patients, including the role ofrecently identified BNP molecular forms.The European multi-national BIOlogy Studyto TAilored Treatment in Chronic HeartFailure (BIOSTAT-CHF) provides an opportunity for the aforementioned analysis, beinga European cohort in which serial sampling ofNPs was done before and after titration of HFmedications according to current Europeanguidelines in a multi-centre, observational,real-world setting.</div

Cutaneous sarcoidosis in a chronic hepatitis C patient receiving pegylated interferon and ribavirin therapy

A 61-year-old Japanese woman suffered from a small, painful, subcutaneous nodule on the sole of her foot that was 10mm across in diameter during pegylated interferon (PEG IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C. Skin biopsy revealed multiple non-caseating granulomas composed of epithelioid histiocytes with multinucleate giant cells, which was consistent with sarcoidosis. Ophthalmologic examination revealed uveitis. Thoracic computed tomography (CT) showed multiple bilateral hilar lymphadenopathies and a diffuse micronodular interstitial pattern of the lungs. Genetic analysis indicated a probable homozygous haplotype of A*02:01-C*15:02-B*51:01-DRB1*16:02-DQB1*05:02 in human leukocyte antigen regions. The patient was observed carefully without any additional medication because no significant systemic symptoms were noted. Combination therapy was continued for 2months afterwards. She was asymptomatic for over 3years of follow up, and repeated hematological and biological investigations and chest CT showed improvement. In conclusion, clinicians should bear sarcoidosis in mind as a complication during PEG IFN and RBV combination therapy. They should also be aware of the usually good prognosis of PEG IFN-induced cutaneous sarcoidosis in order not to prematurely discontinue a treatment necessary for liver disease; maintenance of PEG IFN treatment may be advised with careful follow up.ArticleHEPATOLOGY RESEARCH. 43(7):801-807 (2013)journal articl

Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure (from BIOSTAT-CHF)

Aims: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. Methods and Results: TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2,234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and /or rehospitalisation) at 1,2 and 3 years (HR 1.37–1.51, p≤0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide levels with guideline-based treatment (p&lt;0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes (HR 2.21, 95% CI: 1.43-3.43, p&lt;0.001) compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI: 0.63-2.04, p=0.684 and HR 1.14, 95% CI: 0.64-2.03, p=0.662, respectively). Conclusion: TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmaceutical treatment in contrast to BNP levels which did as expected. Lower TMAO levels regardless of treatment were associated with favorable outcome

Implications of serial measurements of natriuretic peptides in heart failure: insights from BIOSTAT‐CHF

No abstract available

Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS): basics and clinical applications

Background: Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS) has been used for more than 30 years. Compared with other analytical techniques, it offers ease of use, high throughput, robustness, cost-effectiveness, rapid analysis and sensitivity. As advan-tages, current clinical techniques (e.g. immunoassays) are unable to directly measure the biomarker; rather, they measure secondary signals. MALDI-MS has been exten-sively researched for clinical applications, and it is set for a breakthrough as a routine tool for clinical diagnostics.Content: This review reports on the principles of MALDI-MS and discusses current clinical applications and the future clinical prospects for MALDI-MS. Furthermore, the review assesses the limitations currently experienced in clinical assays, the advantages and the impact of MALDI-MS to transform clinical laboratories.Summary: MALDI-MS is widely used in clinical microbiol-ogy for the screening of microbial isolates; however, there is scope to apply MALDI-MS in the diagnosis, prognosis, therapeutic drug monitoring and biopsy imaging in many diseases.Outlook: There is considerable potential for MALDI-MS in clinic as a tool for screening, profiling and imaging because of its high sensitivity and specificity over alterna-tive techniques

Food Preferences of Patients with Citrin Deficiency

Citrin deficiency is characterized by a wide range of symptoms from infancy through adulthood and presents a distinct preference for a diet composed of high protein, high fat, and low carbohydrate. The present study elucidates the important criteria by patients with citrin deficiency for food selection through detailed analysis of their food preferences. The survey was conducted in 70 citrin-deficient patients aged 2–63 years and 55 control subjects aged 2–74 years and inquired about their preference for 435 food items using a scale of 1–4 (the higher, the more favored). The results showed that the foods marked as “dislike” accounted for 36.5% in the patient group, significantly higher than the 16.0% in the controls. The results also showed that patients clearly disliked foods with 20–24 (% of energy) or less protein, 45–54% (of energy) or less fat, and 30–39% (of energy) or more carbohydrate. Multiple regression analysis showed carbohydrates had the strongest influence on patients’ food preference (β = −0.503). It also showed female patients had a stronger aversion to foods with high carbohydrates than males. The protein, fat, and carbohydrate energy ratio (PFC) of highly favored foods among patients was almost the same as the average PFC ratio of their daily diet (protein 20–22: fat 47–51: carbohydrates 28–32). The data strongly suggest that from early infancy, patients start aspiring to a nutritional balance that can compensate for the metabolism dissonance caused by citrin deficiency in every food

Association of gut-related metabolites with outcome in acute heart failure

BackgroundTrimethylamine N-oxide (TMAO), a gut-related metabolite, is associated with heart failure (HF) outcomes. However, TMAO is the final product of a complex metabolic pathway (ie, choline/carnitine) that has never been entirely investigated in HF. The present study investigates a panel of metabolites involved in the TMAO-choline/carnitine metabolic pathway for their associations with outcome in acute HF patients.MethodsIn total, 806 plasma samples from acute HF patients were analyzed for TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, γ-butyrobetaine, crotonobetaine, trimethylamine, betaine aldehyde, choline, and betaine using a developed liquid chromatography-tandem mass spectrometry method. Associations with outcome of all-cause mortality (death) and a composite of all-cause mortality and/or rehospitalization caused by HF (death/HF) at 30 days and 1 year were investigated.ResultsTMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, and γ-butyrobetaine were associated with death and death/HF at 30 days (short term; hazard ratio 1.30-1.49, P≤ .021) and at 1 year (long term; hazard ratio 1.15-1.25, P≤ .026) when adjusted for cardiac risk factors. L-carnitine and acetyl-L-carnitine were superior for short-term outcomes whereas TMAO was the superior metabolite for association with long-term outcomes. Furthermore, acetyl-L-carnitine and L-carnitine were superior for in-hospital mortality and improved risk stratification when combined with current clinical risk scores (ie, Acute Decompensated HEart Failure National REgistry, Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure, and Get With The Guidelines-Heart Failure; odds ratio (OR) ≥ 1.52, P≤ .020).ConclusionsCarnitine-related metabolites show associations with adverse outcomes in acute HF, in particular L-carnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes. Further studies are warranted to investigate the role and implications of carnitine metabolites including intervention in the pathogenesis of HF.</div