Mitochondrial chaotic dynamics: Redox-energetic behavior at the edge of stability

Mitochondria serve multiple key cellular functions, including energy generation, redox balance, and regulation of apoptotic cell death, thus making a major impact on healthy and diseased states. Increasingly recognized is that biological network stability/instability can play critical roles in determining health and disease. We report for the first-time mitochondrial chaotic dynamics, characterizing the conditions leading from stability to chaos in this organelle. Using an experimentally validated computational model of mitochondrial function, we show that complex oscillatory dynamics in key metabolic variables, arising at the “edge” between fully functional and pathological behavior, sets the stage for chaos. Under these conditions, a mild, regular sinusoidal redox forcing perturbation triggers chaotic dynamics with main signature traits such as sensitivity to initial conditions, positive Lyapunov exponents, and strange attractors. At the “edge” mitochondrial chaos is exquisitely sensitive to the antioxidant capacity of matrix Mn superoxide dismutase as well as to the amplitude and frequency of the redox perturbation. These results have potential implications both for mitochondrial signaling determining health maintenance, and pathological transformation, including abnormal cardiac rhythms.publishedVersionKembro, Jackelyn Melissa. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Kembro, Jackelyn Melissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Cortassa, Sonia. National Institutes of Health. NIH · NIA Intramural Research Program; Estados Unidos.Lloyd, David. Cardiff University. School of Biosciences 1; Inglaterra.Sollot, Steven. Johns Hopkins University. Laboratory of Cardiovascular Science; Estados Unidos.Sollot, Steven. Johns Hopkins University. Laboratory of Cardiovascular Science; Estados Unidos

Mass immunisation campaign in a Roma settled community created an opportunity to estimate its size and measles vaccination uptake, Poland, 2009

During a mass immunisation campaign following an outbreak of measles in a Roma community settled in the town of Pulawy, Poland, we performed an estimation of the size of this Roma population and an assessment of its vaccination uptake. We obtained a list of Roma residing in Pulawy from the local municipality and estimated using a simple capture-recapture formula that Pulawy had 377 Roma residents (43% under 20 years old), which was 27% more than the 295 registered at the municipality. During the vaccination campaign, demographic information was recorded that could be linked to information from the municipality list as well as to prior immunisation status. Among the people whose data were recorded during the vaccination campaign, 14% were not registered at the primary healthcare centres, and were therefore deprived of access to healthcare. Among 102 screened subjects under the age of 20 years, 51% were vaccinated according to schedule. Vaccine uptake for the first dose of measles-containing vaccine was 56% (54/96) and for the second dose 37% (18/49). The present study indicates the need to get a better demographic overview of Roma communities living in Poland and to understand the barriers limiting their access to healthcare and social services. Organisation of catch-up immunisations of this vulnerable population is necessary. </jats:p

Volatile organic compounds in uremia.

BACKGROUND: Although "uremic fetor" has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia. METHODS: Breath analysis was performed in 28 adults with an eGFR ≥ 60 ml/min per 1.73 m(2), 26 adults with chronic renal failure corresponding to an eGFR of 10-59 ml/min per 1.73 m(2), and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry. RESULTS: Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10-59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis. CONCLUSION: Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules

Spotlight on measles 2010: A measles outbreak in a Roma population in Pulawy, eastern Poland, June to August 2009

We describe a local indigenous outbreak of measles in a susceptible Roma community, which occurred in Pulawy, a town of 50,000 citizens in the Lubelskie province (eastern Poland) during summer 2009. From 22 June to 30 August 2009, 32 measles cases were reported, and additionally nine possible cases were actively identified. A mass immunisation campaign was organised to stop measles transmission in the Roma community. Active surveillance of rash-febrile illnesses allowed documentation of the impact of mass immunisation in preventing further measles spread in the Roma community, and the surrounding population of Pulawy.</jats:p

Volatile Organic Compounds in Uremia

BACKGROUND: Although “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia. METHODS: Breath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m(2), 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m(2), and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry. RESULTS: Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis. CONCLUSION: Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules

Analytes with signal intensities indicating renal elimination or association to hemodialysis.

<p>Seven of the analytes could be identified by gas chromatography/mass spectrometry (TD-GC/MS). The remaining analytes are described by data of retention time (t_R) and ion mobility (1/K₀). Group A: healthy controls; group B: chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m²; group C: end-stage renal disease (ESRD) prior to hemodialysis; group D: ESRD after hemodialysis. Signal intensities were checked for intergroup differences by univariate ANOVA, p<0.05 was regarded significant.</p

Receiver-operating-characteristic (ROC) curves to distinguish different stages of renal failure.

<p>ROC curves for the sum of the signal intensities of hydroxyacetone, hydroxy-2-butanone, ammonia, 0.5468–17.0, and 0.5985–55.6 in differentiating (A) healthy subjects and patients with chronic renal failure (CRF) corresponding to an eGFR of 10–59 ml/min per 1.73 m² (AUC 0.76), (B) healthy subjects and patients with endstage renal disease (ESRD, AUC 0.83), and (C) healthy subjects and all patients with impaired renal function (CRF and ESRD; AUC 0.80).</p

Study population.

<p>Classification to stages of chronic renal failure according to the National Kidney Foundation. CRF: chronic renal failure BMI: body mass index. eGFR: estimated glomerular filtration rate, calculated by MDRD formula.</p

Signal intensities of exemplary analytes that accumulate during hemodialysis.

<p>Signal intensities of analytes P9 and P11 in 28 healthy controls, 26 patients with chronic renal failure (CRF) stage 2–4 according to K/DOQI-criteria, 28 patients with end-stage renal disease (ESRD, CRF stage 5D) prior to and 22 after hemodialysis. Signal intensities were tested for statistical significance by two-tailed t-tests; *p<0.05, **p<0.01, ***p<0.001.</p