A patient with respiratory toxigenic diphtheria in Greece after more than 30 years.

The introduction of treatment and systematic vaccination has significantly reduced diphtheria mortality; however, toxigenic strains continue to circulate worldwide. The emergence of an indigenous diphtheria case with fatal outcome in Greece, after 30 years, raised challenges for laboratory confirmation, clinical and public health management. Toxigenic Corynebacterium diphtheriae was isolated from an incompletely vaccinated 8-year-old boy with underlying conditions. The child passed away due to respiratory distress syndrome, before the administration of diphtheria antitoxin (DAT). All close contacts in family, school and hospital settings were investigated. Pharyngeal swabs were obtained to determine asymptomatic carriage. Chemoprophylaxis was given for 7 days to all close contacts and a booster dose to those incompletely vaccinated. Testing revealed a classmate, belonging to a subpopulation group (Roma), and incompletely vaccinated, as an asymptomatic carrier with an indistinguishable toxigenic strain (same novel multilocus sequence type, designated ST698). This case highlights the role of asymptomatic carriage, as the entry of toxigenic strains into susceptible populations can put individuals and their environment at risk. Maintenance of high-level epidemiological and microbiological surveillance, implementation of systematic vaccination in children and adults with primary and booster doses, availability of a DAT stockpile, and allowing timely administration are the cornerstone to prevent similar incidents in the future.

Investigation Of Interaction Between Physiological Signals And fMRI Dynamic Functional Connectivity Using Independent Component Analysis.

The blood oxygen level dependent (BOLD) fMRI signal is influenced not only by neuronal activity but also by fluctuations in physiological signals, including respiration, arterial CO2 and heart rate/ heart rate variability (HR/HRV). Even spontaneous physiological signal fluctuations have been shown to influence the BOLD fMRI signal in a regionally specific manner. Consequently, estimates of functional connectivity between different brain regions, performed when the subject is at rest, may be confounded by the effects of physiological signal fluctuations. In addition, resting functional connectivity has been shown to vary with respect to time (dynamic functional connectivity - DFC), with the sources of this variation not fully elucidated. The effect of physiological factors on dynamic (time-varying) resting-state functional connectivity has not been studied extensively, to our knowledge. In our previous study, we investigated the effect of heart rate (HR) and end-tidal CO2 (PETCO2) on the time-varying network degree of three well-described RSNs (DMN, SMN and Visual Network) using mask-based and seed-based analysis, and we identified brain-heart interactions which were more pronounced in specific frequency bands. Here, we extend this work, by estimating DFC and its corresponding network degree for the RSNs, employing a data-driven approach to extract the RSNs (low-and high-dimensional Independent Component Analysis (ICA)), which we subsequently correlate with the characteristics of simultaneously collected physiological signals. The results confirm that physiological signals have a modulatory effect on resting-state, fMRI-based DFC.

Spontaneous physiological variability modulates dynamic functional connectivity in resting-state functional magnetic resonance imaging.

It is well known that the blood oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is influenced-in addition to neuronal activity-by fluctuations in physiological signals, including arterial CO2, respiration and heart rate/heart rate variability (HR/HRV). Even spontaneous fluctuations of the aforementioned physiological signals have been shown to influence the BOLD fMRI signal in a regionally specific manner. Related to this, estimates of functional connectivity between different brain regions, performed when the subject is at rest, may be confounded by the effects of physiological signal fluctuations. Moreover, resting functional connectivity has been shown to vary with respect to time (dynamic functional connectivity), with the sources of this variation not fully elucidated. In this context, we examine the relation between dynamic functional connectivity patterns and the time-varying properties of simultaneously recorded physiological signals (end-tidal CO2 and HR/HRV) using resting-state fMRI measurements from 12 healthy subjects. The results reveal a modulatory effect of the aforementioned physiological signals on the dynamic resting functional connectivity patterns for a number of resting-state networks (default mode network, somatosensory, visual). By using discrete wavelet decomposition, we also show that these modulation effects are more pronounced in specific frequency bands.

Arterial CO2 effects modulate dynamic functional connectivity in resting-state fMRI.

It is well known that the blood-oxygen level dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is influenced - in addition to neuronal activity - by fluctuations in physiological signals, including arterial CO2. For instance, even spontaneous CO2 fluctuations have been shown to influence the BOLD fMRI signal regionally. Related to this, studies of functional connectivity between different brain regions, performed when the subject is at rest, may be confounded by the effects of physiological noise. Moreover, resting functional connectivity has been shown to vary with respect to time (dynamic functional connectivity), with the sources of this variation not fully understood at present. In this context, in the present paper we examine the relation between dynamic functional connectivity patterns and the properties of the end-tidal CO2 signal (PETCO2) using resting-state fMRI measurements from 12 healthy subjects. The results demonstrate that there exists a modulatory effect of the correlation strength between PETCO2 and the BOLD signal on dynamic resting functional connectivity. The extent to which this effect was observed was found to be strongly dependent on the data analysis methodology.