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PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n517). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n510). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

Migraine affects the autonomous nervous system and a recent investigation has also proposed a severe disturbance of dynamic cerebral blood flow regulation in the middle cerebral artery during spontaneous blood pressure oscillations. This study investigates whether dynamic cerebral autoregulation is impaired in persons with migraine among a normal cohort. Out of 94 adults studied to establish normal values for dynamic autoregulation, 19 suffered from migraine according to IHS criteria (10 of them with aura). Transcranial Doppler sonography and fingerplethysmography were used to determine dynamic autoregulation of both middle cerebral arteries following spontaneous low frequency (0.06-0.12 Hz) blood pressure fluctuations (phase and gain of transfer function, correlation coefficient indices Dx and Mx). No significant differences were found for the low frequency variability of blood pressure (power spectral density) and various indices of dynamic cerebral autoregulation between persons with and without migraine. Moreover, no differences were observed between persons with migraine, with and without aura. This study based on a normal cohort does not support the presence of generally impaired cerebral autoregulation dynamics in persons with migraine. Future studies should focus on posterior circulation and particular cerebellar autoregulation.

This study illustrates that the diagnosis of IMD is still very problematic and lacks objectivity. Together with GM in BAL, the PCRs may prove an addition to the current available diagnostic armamentarium in IMD because of their ability to identify molds on a species level.

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