Endocarditis due to Tropheryma whipplei: rapid detection, limited genetic diversity, and long-term clinical outcome in a local experience

The characteristic features of Whipple's disease include abdominal pain, diarrhoea, wasting, and arthralgias, with the causative agent, Tropheryma whipplei, being detected mainly in intestinal biopsies. PCR technology has led to the identification of T. whipplei in specimens from various other locations, including the central nervous system and the heart. T. whipplei is now recognized as one of the causes of culture-negative endocarditis, and endocarditis can be the only manifestation of the infection with T. whipplei. Although it is considered a rare disease, the true incidence of endocarditis due to T. whipplei is not clearly established. With the increasing use of molecular methods, it is likely that T. whipplei will be more frequently identified. Questions also remain about the genetic variability of T. whipplei strains, optimal diagnostic procedures and therapeutic options. In the present study, we provide clinical data on four new patients with documented endocarditis due to T. whipplei in the context of the available published literature. There was no clinical involvement of the gastrointestinal tract. Genetic analysis of the T. whipplei strains with DNA isolated from the excised heart valves revealed little to no genetic variability. In a selected case, we describe acridine orange staining for early detection of the disease, prompting early adaptation of the antibiotic therapy. We provide long-term follow-up data on the patients. In our hands, an initial 2-week course of intravenous antibiotics followed by cotrimoxazole for at least 1 year was a suitable treatment option for T. whipplei endocarditis.

Software-based detection of atrial fibrillation in long-term ECGs

Background Atrial fibrillation (AF) is common and may have severe consequences. Continuous long-term electrocardiogram (ECG) is widely used for AF screening. Recently, commercial ECG analysis software was launched, which automatically detects AF in long-term ECGs. It has been claimed that such tools offer reliable AF screening and save time for ECG analysis. However, this has not been investigated in a real-life patient cohort. Objective To investigate the performance of automatic software-based screening for AF in long-term ECGs. Methods Two independent physicians manually screened 22,601 hours of continuous long-term ECGs from 150 patients for AF. Presence, number, and duration of AF episodes were registered. Subsequently, the recordings were screened for AF by an established ECG analysis software (Pathfinder SL), and its performance was validated against the thorough manual analysis (gold standard). Results Sensitivity and specificity for AF detection was 98.5% (95% confidence interval 91.72%–99.96%) and 80.21% (95% confidence interval 70.83%–87.64%), respectively. Software-based AF detection was inferior to manual analysis by physicians (P < .0001). Median AF duration was underestimated (19.4 hours vs 22.1 hours; P < .001) and median number of AF episodes was overestimated (32 episodes vs 2 episodes; P < .001) by the software. In comparison to extensive quantitative manual ECG analysis, software-based analysis saved time (2 minutes vs 19 minutes; P < .001). Conclusion Owing to its high sensitivity and ability to save time, software-based ECG analysis may be used as a screening tool for AF. An additional manual confirmatory analysis may be required to reduce the number of false-positive findings.

The near babylonian speech confusion in early detection of psychosis

It is barely 15 years since, in 1996, the issue theme of Schizophrenia Bulletin (Vol 22, 2) “Early Detection, and Intervention in Schizophrenia” signified the commencement of this field of research. Since that time the field of early detection research has developed rapidly and it may be translated into clinical practice by the introduction of an Attenuated Psychosis Syndrome in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-5) (www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=412#). Attenuated psychotic symptoms (APS) had first been suggested as a clinical predictor of first-episode psychosis by the Personal Assessment and Crisis Evaluation (PACE) Clinic group as part of the ultrahigh risk (UHR) criteria.1 The term ultrahigh risk became broadly accepted for this set of criteria for imminent risk of developing psychosis in the late 1990s. The use of the term “prodrome” for a state characterized by at-risk (AR) criteria was criticized as a retrospective concept inevitably followed by the full-blown disorder.1 Although alternative terms have been suggested, prodrome is still used in prospective studies (eg, prodromally symptomatic, potentially or putatively prodromal, prodrome-like state/symptoms). Some alternative suggestions such as prepsychotic state/symptoms, subthreshold psychotic symptoms, early psychosis, subsyndromal psychosis, hypopsychosis, or subpsychosis were short-lived. Other terms still in use include UHR, at-risk mental state (ARMS), AR, high risk, clinical high risk (CHR), or early and late AR state. Further, the term psychotic-like experiences (PLEs) has recently (re-)entered early detection research. …

Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay

Background Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. Methods Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). Results Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. Conclusions DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the "PCR era", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.

High-resolution esophageal long-term ECG allows detailed atrial wave morphology analysis in case of atrial ectopic beats

Detection of arrhythmic atrial beats in surface ECGs can be challenging when they are masked by the R or T wave, or do not affect the RR-interval. Here, we present a solution using a high-resolution esophageal long-term ECG that offers a detailed view on the atrial electrical activity. The recorded ECG shows atrial ectopic beats with long coupling intervals, which can only be successfully classified using additional morphology criteria. Esophageal high-resolution ECGs provide this information, whereas surface long-term ECGs show poor atrial signal quality. This new method is a promising tool for the long-term rhythm monitoring with software-based automatic classification of atrial beats.

The role of cell death and myofibrillar damage in contractile dysfunction of long-term cultured adult cardiomyocytes exposed to doxorubicin

In failing hearts cardiomyocytes undergo alterations in cytoskeleton structure, contractility and viability. It is not known presently, how stress-induced changes of myofibrils correlate with markers for cell death and contractile function in cardiomyocytes. Therefore, we have studied the progression of contractile dysfunction, myofibrillar damage and cell death in cultured adult cardiomyocytes exposed to the cancer therapy doxorubicin. We demonstrate, that long-term cultured adult cardiomyocytes, a well-established model for the study of myofibrillar structure and effects of growth factors, can also be used to assess contractility and calcium handling. Adult rat ventricular myocytes (ARVM) were isolated and cultured for a total of 14 days in serum containing medium. The organization of calcium-handling proteins and myofibrillar structure in freshly isolated and in long-term cultured adult cardiomyocytes was studied by immunofluorescence and electron microscopy. Excitation contraction-coupling was analyzed by fura 2 and video edge detection in electrically paced cardiomyocytes forming a monolayer, and cell death and viability was measured by TUNEL assay, LDH release, MTT assay, and Western blot for LC3. Adult cardiomyocytes treated with Doxo showed apoptosis and necrosis only at supraclinical concentrations. Treated cells displayed merely alterations in cytoskeleton organization and integrity concomitant with contractile dysfunction and up-regulation of autophagosome formation, but no change in total sarcomeric protein content. We propose, that myofibrillar damage contributes to contractile dysfunction prior to cell death in adult cardiomyocytes exposed to clinically relevant concentrations of anthracyclines.

A new optical detection method to assess the erosion inhibition by in vitro salivary pellicle layer

OBJECTIVES Application of the recently developed optical method based on the monitoring of the specular reflection intensity to study the protective potential of the salivary pellicle layer against early enamel erosion. METHODS The erosion progression was compared between two treatment groups: enamel samples coated by the 15 h-in vitro-formed salivary pellicle layer (group P, n=90) and the non-coated enamel surfaces (control group C, n=90). Different severity of the erosive impact was modelled by the enamel incubation in 1% citric acid (pH=3.6) for 2, 4, 8, 10 or 15 min. Erosion quantification was performed by the optical method as well as by the microhardness and calcium release analyses. RESULTS Optical assessment of the erosion progression showed erosion inhibition by the in vitro salivary pellicle in short term acidic treatments (≤ 4 min) which was also confirmed by microhardness measurements proving significantly less (p<0.05) enamel softening in the group P at 2 and 4 min of erosion compared to the group C. SEM images demonstrated less etched enamel interfaces in the group P at short erosion durations as well. CONCLUSIONS Monitoring of the specular reflection intensity can be successfully applied to quantify early erosion progression in comparative studies. In vitro salivary pellicle (2h) provides erosion inhibition but only in short term acidic exposures. CLINICAL SIGNIFICANCE The proposed optical technique is a promising tool for the fast and non-invasive erosion quantification in clinical studies.

Intelligence is related to specific processes in visual change detection: Fixed-links modeling of hit rate and reaction time

By means of fixed-links modeling, the present study identified different processes of visual short-term memory (VSTM) functioning and investigated how these processes are related to intelligence. We conducted an experiment where the participants were presented with a color change detection task. Task complexity was manipulated through varying the number of presented stimuli (set size). We collected hit rate and reaction time (RT) as indicators for the amount of information retained in VSTM and speed of VSTM scanning, respectively. Due to the impurity of these measures, however, the variability in hit rate and RT was assumed to consist not only of genuine variance due to individual differences in VSTM retention and VSTM scanning but also of other, non-experimental portions of variance. Therefore, we identified two qualitatively different types of components for both hit rate and RT: (1) non-experimental components representing processes that remained constant irrespective of set size and (2) experimental components reflecting processes that increased as a function of set size. For RT, intelligence was negatively associated with the non-experimental components, but was unrelated to the experimental components assumed to represent variability in VSTM scanning speed. This finding indicates that individual differences in basic processing speed, rather than in speed of VSTM scanning, differentiates between high- and low-intelligent individuals. For hit rate, the experimental component constituting individual differences in VSTM retention was positively related to intelligence. The non-experimental components of hit rate, representing variability in basal processes, however, were not associated with intelligence. By decomposing VSTM functioning into non-experimental and experimental components, significant associations with intelligence were revealed that otherwise might have been obscured.

The assessment of visual short-term memory in considering the underlying processes and their relation to psychometric intelligence

By means of fixed-links modeling the present study assessed processes involved in visual short-term memory functioning and investigates how these processes are related to intelligence. Using a color change detection task, short-term memory demands increased across three experimental conditions as a function of number of presented stimuli. We measured amount of information retained in visual short-term memory by hit rate as well as speed of visual short-term memory scanning by reaction time. For both measures, fixed-links modeling revealed a constant process reflecting processes irrespective of task manipulation as well as two increasing processes reflecting the increasing short-term memory demands. For visual short-term memory scanning, a negative association between intelligence and the constant process was found but no relationship between intelligence and the increasing processes. Thus, basic processing speed, rather than speed influenced by visual short-term memory demands, differentiates between high- and low-intelligent individuals. Intelligence was positively related to the experimental processes of shortterm memory retention but not to the constant process. In sum, significant associations with intelligence were only obtained when the specific processes of short-term memory were decomposed emphasizing the importance of a thorough assessment of cognitive processes when investigating their relation to intelligence.

An optimized lead system for long-term esophageal electrocardiography

Long-term electrocardiography (ECG) featuring adequate atrial and ventricular signal quality is highly desirable. Routinely used surface leads are limited in atrial signal sensitivity and recording capability impeding complete ECG delineation, i.e. in the presence of supraventricular arrhythmias. Long-term esophageal ECG might overcome these limitations but requires a dedicated lead system and recorder design. To this end, we analysed multiple-lead esophageal ECGs with respect to signal quality by describing the ECG waves as a function of the insertion level, interelectrode distance, electrode shape and amplifier's input range. The results derived from clinical data show that two bipolar esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a ventricular lead with long (80 mm) interelectrode distance provide non-inferior ventricular signal strength and superior atrial signal strength compared to standard surface lead II. High atrial signal slope in particular is observed with the atrial esophageal lead. The proposed esophageal lead system in combination with an increased recorder input range of ±20 mV minimizes signal loss due to excessive electrode motion typically observed in esophageal ECGs. The design proposal might help to standardize long-term esophageal ECG registrations and facilitate novel ECG classification systems based on the independent detection of ventricular and atrial electrical activity.

Extraversion and short-term memory for chromatic stimuli: an event-related potential analysis.

The present study investigated extraversion-related individual differences in visual short-term memory (VSTM) functioning. Event related potentials were recorded from 50 introverts and 50 extraverts while they performed a VSTM task based on a color-change detection paradigm with three different set sizes. Although introverts and extraverts showed almost identical hit rates and reaction times, introverts displayed larger N1 amplitudes than extraverts independent of color change or set size. Extraverts also showed larger P3 amplitudes compared to introverts when there was a color change, whereas no extraversion-related difference in P3 amplitude was found in the no-change condition. Our findings provided the first experimental evidence that introverts' greater reactivity to punctuate physical stimulation, as indicated by larger N1 amplitude, also holds for complex visual stimulus patterns. Furthermore, P3 amplitude in the change condition was larger for extraverts than introverts suggesting higher sensitivity to context change. Finally, there were no extraversion-related differences in P3 amplitude dependent on set size. This latter finding does not support the resource allocation explanation as a source of differences between introverts and extraverts.