Hantavirus infections in Europe and their impact on public health

Hantaviruses (genus Hantavirus, family Bunyaviridae) are enveloped tri‐segmented negative‐stranded RNA viruses each carried by a specific rodent or insectivore host species. Several different hantaviruses known to infect humans circulate in Europe. The most common is Puumala (PUUV) carried by the bank vole; another two important, genetically closely related ones are Dobrava–Belgrade (DOBV) and Saaremaa viruses (SAAV) carried by Apodemus mice (species names follow the International Committee on Taxonomy of Viruses nomenclature). Of the two hantaviral diseases, hemorrhagic fever with renal syndrome (HFRS) and hantaviral cardiopulmonary syndrome, the European viruses cause only HFRS: DOBV with often severe symptoms and a high case fatality rate, and PUUV and SAAV more often mild disease. More than 10,000 HFRS cases are diagnosed annually in Europe and in increasing numbers. Whether this is because of increasing recognition by the medical community or due to environmental factors such as climate change, or both, is not known. Nevertheless, in large areas of Europe, the population has a considerable seroprevalence but only relatively few HFRS cases are reported. Moreover, no epidemiological data are available from many countries. We know now that cardiac, pulmonary, ocular and hormonal disorders are, besides renal changes, common during the acute stage of PUUV and DOBV infection. About 5% of hospitalized PUUV and 16%–48% of DOBV patients require dialysis and some prolonged intensive‐care treatment. Although PUUV–HFRS has a low case fatality rate, complications and long‐term hormonal, renal, and cardiovascular consequences commonly occur. No vaccine or specific therapy is in general use in Europe. We conclude that hantaviruses have a significant impact on public health in Europe. Copyright © 2012 John Wiley & Sons, Ltd.     

Exchange-influenced T2rho contrast in human brain images measured with adiabatic radio frequency pulses.

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI.     

Effects of genioglossal muscle advancement on speech: an acoustic study of vowel sounds.

OBJECTIVE: The effects of the genioglossal muscle advancement on phonetic quality of speech were studied analyzing the acoustic features of vowel sounds. STUDY DESIGN AND SETTING: The study group consisted of 5 men suffering from partial upper airway obstruction during sleep. To prevent tongue base collapse, genioglossal muscle advancement was made with chin osteotomy without hyoid myotomy and suspension. The speech material consisted of 8 vowels produced in sentence context repeated 10 times before the operation, and 10 days and 6 weeks after the operation. The acoustic features of vowels were analyzed. RESULTS: The operation had no significant effects on vowel quality. Only for 2 of the subjects the pitches changed systematically due to the operation. CONCLUSION: According to the acoustic analysis, genioglossal muscle advancement with chin osteotomy has no effects on vowel production. Some short-term changes were observed, but these changes were highly individual. SIGNIFICANCE: The operation seems to have no potential to change vowel production.     

Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion.     

Family-based association study of the restless legs syndrome loci 2 and 3 in a European population.

Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family-based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846-D9S171 in a subset of South European trios and with a haplotype at D9S156-D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS.     

Acoustic comparison of vowel sounds produced before and after orthognathic surgery for mandibular advancement.

PURPOSE: The effects of orthognathic surgery on the phonetic quality of speech were studied by analyzing the main acoustic features of vowel sounds. PATIENTS AND METHODS: Five men with dentofacial deformities undergoing surgical operation for correction of malocclusion were enrolled in the study. The speech material consisted of 8 vowels in sentence context. Every utterance was repeated 10 times in 3 different sessions: before the operation, 6 weeks after the operation, and 30 weeks after the operation. The acoustic features (F1, F2, F0, duration) of vowels were measured and analyzed. RESULTS: At the group level, no significant acoustic changes were found between the 3 different sessions in any parameter measured (all F values <1). The results show that the operation had individual and variable effects on vowel quality, ranging from slightly affected to completely unaffected. The 2 lowest vocal-tract resonances changed in frequency for 2 of the subjects, and 1 subject had short-term changes returning to the presurgical level. Significant changes of F0 were observed for 1 subject, and 3 of the subjects had short-term changes. No significant changes were found for duration. One subject had no significant changes in any parameter measured. CONCLUSIONS: No long-lasting perceptually significant changes were identified in vowel production in patients undergoing a variety of orthognathic procedures. The facial skeleton (consisting of palate, maxilla, mandible, dentition, nasal cavity, etc) imposes direct limits on the morphology of the resonating vocal tract cavities, and is therefore of immediate relevance to both speech articulation and acoustics.     

Reliability of an inclinometric method for assessment of body sway.

Falling related injuries are associated with morbidity and mortality among older persons. An accurate and comparable assessment of postural sway may offer a method for detecting those at risk for falling. Our purpose was to assess the validity and repeatability of an inclinometric method in assessing postural sway during quiet standing. To assess repeatability, 51 elderly women (aged 72 to 74 years) were measured twice by the same tester. To assess validity, postural sway in 29 elderly subjects (aged 69 to 86 years) was assessed using simultaneously the inclinometric and a force platform method. The test-retest reliability correlation of the inclinometric method was high for sway path length (coefficient of determination r(2) = 0.683), and moderate for sway area (r(2) = 0.500) and the analysis revealed no sign of bias. The correlation was moderate between the values of the inclinometric sway path length and those of the force platform for antero-posterior (r(2) = 0.466), lateral (r(2) = 0.694) and combined lateral and antero-posterior (r(2) = 0.623) directional sway movements. The inclinometric method offers an accurate and repeatable method for assessing postural sway and may be a feasible method to be used in the risk stratification of falling.     

From traumatic brain injury to posttraumatic epilepsy: What animal models tell us about the process and treatment options

A large number of animal models of traumatic brain injury (TBI) are already available for studies on mechanisms and experimental treatments of TBI. Immediate and early seizures have been described in many of these models with focal or mixed type (both gray and white matter damage) injury. Recent long-term video-electroencephalography (EEG) monitoring studies have demonstrated that TBI produced by lateral fluid-percussion injury in rats results in the development of late seizures, that is, epilepsy. These animals develop hippocampal alterations that are well described in status epilepticus–induced spontaneous seizure models and human posttraumatic epilepsy (PTE). In addition, these rats have damage ipsilaterally in the cortical injury site and thalamus. Although studies in the trauma field provide a large amount of information about the molecular and cellular alterations corresponding to the immediate and early phases of PTE, chronic studies relevant to the epileptogenesis phase are sparse. Moreover, despite the multiple preclinical pharmacologic and cell therapy trials, there is no information available describing whether these therapeutic approaches aimed at improving posttraumatic recovery would also affect the development of lowered seizure threshold and epilepsy. To make progress, there is an obvious need for information exchange between the trauma and epilepsy fields. In addition, the inclusion of epilepsy as an outcome measure in preclinical trials aiming at improving somatomotor and cognitive recovery after TBI would provide valuable information about possible new avenues for antiepileptogenic interventions and disease modification after TBI.     

Dynamic dephasing changes in developing ischemic cerebral infarction in rats studied by Carr-Purcell T2 magnetic resonance imaging.

Carr-Purcell (CP) T(2) MRI with adiabatic pulses, acquired with varying interecho interval (tau(CP)), was used to study the time course of T(2) and relative dynamic-dephasing contrast in the rat brain. Exposure to 30 min of middle cerebral artery occlusion (MCAo) resulted in an irreversible increase in absolute CP-T(2) relaxation times. This was not associated with signal change in the relative dynamic-dephasing images, as computed by subtracting short tau(CP) CP-T(2) images from long tau(CP) images and normalizing for long tau(CP) images. A day after MCAo strong CP-T(2) hyperintensity and low apparent diffusion coefficient were evident in the striatum with a decline in relative dynamic-dephasing contrast. Low dynamic dephasing contrast prevailed in striatum until day 5 post-MCAo, returning to control levels with similar time course to normalizing T(2) and diffusion. The present results show a novel behavior of dynamic-dephasing contrast in poststroke brain tissue, providing data to assess the age of infarction in association to T(2) images.     

Amylin competes for binding sites of CGRP in the chamber angle and uvea of monkey, cat, and pig eye.

Calcitonin gene-related peptide (CGRP) binding sites have been identified previously in the eyes of monkey, cat, pig, and guinea pig. In this study, the ability of cat, human, and rat amylins to displace the binding of CGRP in the anterior part of the eye of monkey, cat, and pig was studied. The location and displacement of 125I-hCGRPalpha by amylins as concentrations of 1-1000 nM were studied in cryosections by autoradiography. In the monkey eye, cat and rat amylins were able to compete for the binding sites of CGRP in ciliary muscle and ciliary processes. In the cat eye, cat and human amylins clearly displaced CGRP binding from ciliary muscle, ciliary processes, iris, and chamber angle. Furthermore, rat amylin clearly displaced CGRP binding from ciliary muscle and ciliary processes. In the pig eye, cat, human, and rat amylins competed for the binding sites of CGRP in ciliary muscle, ciliary processes, iris, and limbal conjunctiva. Specific amylin receptors or the possible physiological role of amylin in the eye have not hitherto been reported. It seems, however, that amylin can bind to ocular CGRP receptors and thus probably plays a role in the regulation of the same functions as CGRP, (e.g., aqueous humor outflow).