Assessment of Enterovirus Antibodies during Early Childhood Using a Multiplex Immunoassay.

Enteroviruses are a group of positive single-stranded viruses that belong to the Picornaviridae family. They regularly infect humans and cause symptoms ranging from the common cold and hand-foot-and-mouth disease to life-threatening conditions, such as dilated cardiomyopathy and poliomyelitis. Enteroviruses have also been associated with chronic immune-mediated diseases, such as type 1 diabetes, celiac disease, and asthma. Studying these disease-pathogen connections is challenging due to the high prevalence of enterovirus infections in the population and the transient appearance of the virus during the acute infection phase, which limit the identification of the causative agent via methods based on the virus genome. Serological assays can detect the antibodies induced by acute and past infections, which is useful when direct virus detection is not possible. We describe in this immuno-epidemiological study how the antibody levels against VP1 proteins from eight different enterovirus types, representing all seven of the human infecting enterovirus species, vary over time. VP1 responses first significantly (P < 0.001) decline until 6 months of age, reflecting maternal antibodies, and they then start to increase as the infections accumulate and the immune system develops. All 58 children in this study were selected from the DiabImmnune cohort for having PCR-confirmed enterovirus infections. Additionally, we show that there is great, although not complete, cross-reactivity of VP1 proteins from different enteroviruses and that the response against 3C-pro could reasonably well reflect the recent Enterovirus infection history (ρ = 0.94, P = 0.017). The serological analysis of enterovirus antibodies in sera from children paves the way for the development of tools for monitoring the Enterovirus epidemics and associated diseases. IMPORTANCE Enteroviruses cause a wide variety of symptoms ranging from a mild rash and the common cold to paralyzing poliomyelitis. While enteroviruses are among the most common human pathogens, there is a need for new, affordable serological assays with which to study pathogen-disease connections in large cohorts, as enteroviruses have been linked to several chronic illnesses, such as type 1 diabetes mellitus and asthma exacerbations. However, proving causality remains an issue. In this study, we describe the use of an easily customizable multiplexed assay that is based on structural and nonstructural enterovirus proteins to study antibody responses in a cohort of 58 children from birth to 3 years of age. We demonstrate how declining maternal antibody levels can obscure the serological detection of enteroviruses before the age of six months and how antibody responses to nonstructural enterovirus proteins could be interesting targets for serodiagnosis.

Desmosterol accumulation in users of amiodarone.

BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. OBJECTIVE: Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. METHODS: The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population. Cholesterol metabolism was evaluated by analysis of serum noncholesterol sterols by gas-liquid chromatography and gas chromatography-mass spectrometry. RESULTS: Comparisons of serum lipids and noncholesterol sterols across the three groups showed increased serum triglyceride in users of amiodarone but no statistically significant group differences in total, LDL or HDL cholesterol or serum proprotein convertase subtilisin/kexin type 9 concentrations. Nor did the groups differ in the ratios of cholestanol or plant sterols to cholesterol in serum, suggesting that cholesterol absorption was unaltered. However, all users of amiodarone had very markedly elevated serum desmosterol concentrations: the desmosterol-to-cholesterol ratio (102 × µmol mmol-1 ) averaged 1030.7 ± 115.7 (mean ± SE) in the amiodarone + group versus 82.7 ± 3.4 and 75.9 ± 1.4 in the amiodarone - and the population control groups (P < 0.001), respectively. CONCLUSION: Use of amiodarone was associated with on average 12-fold serum desmosterol concentrations compared with the control groups. This observation is fully novel and suggests that amiodarone interferes with the conversion of desmosterol to cholesterol in the cholesterol synthesis pathway. Whether accumulation of desmosterol plays a role in amiodarone-induced hepatotoxicity deserves to be studied in the future.

The outcome of short- and long-term psychotherapy 10 years after start of treatment.

BACKGROUND: Empirical evidence on whether patients' mental health and functioning will be more improved after long-term than short-term therapy is scarce. We addressed this question in a clinical trial with a long follow-up. METHOD: In the Helsinki Psychotherapy Study, 326 out-patients with mood or anxiety disorder were randomly assigned to long-term psychodynamic psychotherapy (LPP), short-term psychodynamic psychotherapy (SPP) or solution-focused therapy (SFT) and were followed for 10 years. The outcome measures were psychiatric symptoms, work ability, personality and social functioning, need for treatment, and remission. RESULTS: At the end of the follow-up, altogether 74% of the patients were free from clinically elevated psychiatric symptoms. Compared with SPP, LPP showed greater reductions in symptoms, greater improvement in work ability and higher remission rates. A similar difference in symptoms and work ability was observed in comparison with SFT after adjustment for violations of treatment standards. No notable differences in effectiveness between SFT and SPP were observed. The prevalence of auxiliary treatment was relatively high, 47% in SFT, 58% in SPP and 33% in LPP, and, accordingly, the remission rates for general symptoms were 55, 45 and 62%, respectively. CONCLUSIONS: After 10 years of follow-up, the benefits of LPP in comparison with the short-term therapies are rather small, though significant in symptoms and work ability, possibly due to more frequent use of auxiliary therapy in the short-term therapy groups. Further studies should focus on the choice of optimal length of therapy and the selection of factors predicting outcome of short- v. long-term therapy.

Diagnosing isolated cardiac sarcoidosis.

OBJECTIVES: Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging-guided biopsies in clinically isolated CS. METHODS: We retrospectively reviewed the medical records, laboratory test results, imaging studies and pathological analyses of 74 patients with either histologically proven or clinically probable CS at our institution between January 2000 and December 2010. RESULTS: Fifty-two patients had histologically proven CS, of whom 33 (26 women) had disease that was clinically isolated to the heart. Sarcoidosis was detected in the first EMB in 10 of the 31 patients who underwent biopsy. CS was found by repeated EMBs, targeted by cardiac imaging, in seven additional patients, and 11 patients were diagnosed by sampling 18-F-fluorodeoxyglucose position emission tomography-positive mediastinal lymph nodes at mediastinoscopy. Together, the first biopsy (cardiac or mediastinal lymph node) provided the diagnosis in 34%, the second biopsy in 31% and the third in 22% of biopsied patients with isolated CS. Four (13%) of the remaining diagnosis were made after cardiac transplantation and one in a patient who did not undergo biopsy) at autopsy after sudden cardiac death. CONCLUSIONS: Cardiac sarcoidosis may present without clinically apparent disease in other organs. At least two-thirds of patients remain undiagnosed after a single EMB session. The detection rate can be improved by repeated and imaging-guided cardiac or mediastinal lymph-node biopsies. Nevertheless, false-negative biopsy results remain a problem in CS patients with no apparent extracardiac disease.

Online classification of single EEG trials during finger movements.

Many offline studies have explored the feasibility of EEG potentials related to single limb movements for a brain-computer interface (BCI) control signal. However, only few functional online single-trial BCI systems have been reported. We investigated whether inexperienced subjects could control a BCI accurately by means of visually-cued left versus right index finger movements, performed every 2 s, after only a 20-min training period. Ten subjects tried to move a circle from the center to a target location at the left or right side of the computer screen by moving their left or right index finger. The classifier was updated after each trial using the correct class labels, enabling up-to-date feedback to the subjects throughout the training. Therefore, a separate data collection session for optimizing the classification algorithm was not needed. When the performance of the BCI was tested, the classifier was not updated. Seven of the ten subjects were able to control the BCI well. They could choose the correct target in 84%-100% of the cases, 3.5-7.7 times a minute. Their mean single trial classification rate was 80% and bit rate 10 bits/min. These results encourage the development of BCIs for paralyzed persons based on detection of single-trial movement attempts.

Trichostrongylina (Nematoda) from Malagasy Muridae. III--description of a new species of Heligmonoides Baylis, 1928 (Heligmonellidae) parasitic in Mus musculus.

Heligmonoides variabilis n. sp. (Heligmosomoidea, Nippostrongylinae) a parasite of Mus musculus from Madagascar is related to H. afghanus (Tenora, 1969), H. ikeharai Hasegawa, 1990 and H. josephi (Wertheim & Durette-Desset, 1976), all having the dorsal ray divided anterior to the arising of rays 8. H. ikeharai a parasite of Tokudaia muenninki (Muridae) from Japan is the most closely related species with rays 8 arising at mid-length along the dorsal ray. It is differentiated from the new species by very long spicules (almost half of body length) and by the length of the vestibule (almost one millimeter). A new definition of the genus Heligmonoides Baylis, 1928 is proposed with a dichotomic key of the species. The biogeographic distribution and the host spectrum of the genus are described.

Results and future of carotid endarterectomy in a medium-sized Finnish central hospital.

BACKGROUND AND AIMS: Carotid endarterectomies (CEA) should, by general agreement, be performed only at specialised institutions and on patients who are expected to have a low rate of complications, i.e., a 6% surgical risk for patients with symptomatic and a 3% risk for patients with asymptomatic carotid artery disease. We have reviewed the midterm results after CEA in a medium-sized Finnish central hospital to audit whether our results fulfil current quality standards. PATIENTS, MATERIALS AND METHODS: There were 116 consecutively operated patients at the Päijät-Häme Central Hospital during the years 1999-2003 on whom 122 CEAs were made. All CEAs were performed by conventional methods and shunts and patches were used when necessary. RESULTS: The overall survival rate was 81.0% during the 3.6 +/- 1.5 years [range 1.3-6.3 years] follow-up. The incidence of early major stroke was 2.5% and of late major stroke 1.6%. Other complications included cranial nerve deficit (2.5%), wound haematoma (3.3%) and postoperative hypertension (3.3%) or hypotension (2.5%). Significant changes in medication were needed after surgery in several patient subgroups. CONCLUSIONS: The results of CEA at the Päijät-Häme Central Hospital are at least acceptable. The primary prevention of strokes with pharmacotherapy needs aggressive improvement.

On correlation between single-trial ERP and GSR responses: a principal component regression approach.

In this study we investigate the correlation between single-trial evoked brain responses and galvanic skin responses (GSR). The correlation between the two signals is examined by using a modified principal component regression based approach. A potential application of the study is to utilize the GSR measurements in a form of a prior information in the estimation of the brain potentials when only small number of trials is available.

Trichostrongylina (Nematoda) from Malagasy muridae. II--Description of two new species of Heligmonina (Heligmonellidae) in Nesomys rufus and Eliurus tanala.

Two new species of Heligmonellidae from Madagascar are described, Heligmonina madagascariensis n. sp. in Nesomys rufus and Heligmonina tanala n. sp. in Eliurus tanala. Both species belong to the Heligmonina species with a pattern of type 1-3-1 for the right lobe of the caudal bursa and 1-4 for the left lobe. In H. madagascariensis, H. dupuisi (Desset, 1964) and H. praomyos Baylis, 1928, left ray 6 arises before ray 3 from the common trunk to rays 3 to 6 while in H. tanala and the other species, it arises at the same level. H. madagascariensis is differentiated from H. dupuisi and H. praomyos by the symmetry of the branches of the dorsal ray. H. tanala is differentiated from H. malacomys Sakka & Durette-Desset, 1988, the closely related species by a different pattern of the cuticular ridges at mid-body, by the sharpness of the tips of the spicules and by the ratio of the length of the spicules on the length of the body (6.9, 8.8% versus 25-27.8%). Heligmonina chippauxi (Desset, 1964) a parasite of Oenomys hypoxanthus from the Republic of Central Africa is considered a valid species.

Nightmares as predictors of suicide.

STUDY OBJECTIVES: To examine the relationship between the frequency of nightmares and the risk of suicide. DESIGN AND SETTING: A prospective follow-up study in a general population of Finland starting in 1972. PARTICIPANTS: A total of 36,211 subjects (17,700 men and 18,511 women) aged 25-64 years at baseline. INTERVENTIONS: N/A. MEASUREMENTS: The study included self-administered questionnaires (mainly questions on socio-economic factors, medical history, health behavior, and psychosocial factors) and health examination at the local primary healthcare center. The frequency of nightmares was estimated. The subjects were followed until Dec. 31, 1995, or death. Information on deaths caused by suicide (n=159) or other self-inflicted injury was obtained from the National Death Register by computerized record linkage using the national personal identification code assigned to every Finnish resident. Using the Cox proportional hazards regression model we controlled for several potential confounding factors. RESULTS: The frequency of nightmares was directly related to the risk of suicide. Among subjects having nightmares occasionally the adjusted relative risk of suicide was 57% higher, and among those reporting frequent nightmares 105% higher compared with subjects reporting no nightmares at all. CONCLUSIONS: This is the first study to report a direct and graded association between the frequency of nightmares and death from suicide in a general population.

Male suicide mortality in eastern Finland--urban-rural changes during a 10-year period between 1988 and 1997.

AIMS: To investigate urban-rural differences in male suicide mortality between 1988 and 1997 in the province of Kuopio in eastern Finland. METHODS: Male suicide mortality between 1988 and 1997 was studied in eastern Finland. The data were collected from official autopsy reports. Age, marital status, household type, place of death, method of suicide and the region within the county were analysed. RESULTS: The age-adjusted male suicide mortality remained quite constant at 67 and 65/100,000 (> 15 years of age) in 1988 and 1997, respectively. In urban areas, a decline in suicide rates was noted in all age groups of men, whereas in rural areas, after an initial decline, a marked increase took place during the last years of the study period, especially among middle-aged and elderly men. This coincided with the time of recovery from an economic recession in Finland that particularly affected rural areas. CONCLUSION: Male suicide mortality may be regionally diverging in Finland.

Effects of maternity on auditory event-related potentials to human sound.

Auditory event-related brain potentials (ERPs) were recorded in response to an emotional (a baby's cry) and a neutral (a word) stimulus in a group of mothers 2-5 days after childbirth (n = 20) and in control women (n = 18) who were not in the state of early motherhood. For each mother, her own infant's cry was recorded and used as the cry stimulus, whereas a strange baby's cry was used for control women. The word stimulus was identical for both groups. Stimuli were presented in intermittent trains in order to study the arousal responses to the first stimuli of the trains, and refractoriness of ERPs during stimulus repetition. The N100 responses were significantly larger in amplitude in mothers than in control women, not only to the emotional cry stimuli but also to the neutral word stimuli. The finding suggests a general increase in alertness and arousal in mothers, which may be necessary in enabling the mother to be continuously alert to her infant's needs. This allows good care of the infant and may be essential in building an emotional tie between the mother and her child.

SPECT and neuropsychological performance in severe depression treated with ECT.

BACKGROUND: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. METHODS: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. RESULTS: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. CONCLUSIONS: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Loss of time-organized sympathetic skin responses in acute psychosis.

The aim of this study was to differentiate the response pattern characteristics of sympathetic skin responses (SSR) between unmedicated first psychotic subjects and healthy controls. We recorded SSR to novel auditory stimuli in 13 psychotic subjects and in 19 controls. There was no constant delay between a sudden change in the acoustic surroundings and SSR in psychotic subjects, whereas regularly this delay was 1.3 to 1.8 seconds in controls. The validity of the test was evaluated by blind rating responses to two categories. The lack of a regular time delay between a novel auditory stimulus and SSR suggests a timing disturbance in the neural networks regulating the autonomic nervous system responses in acute psychosis. Our finding and method may have future implications in evaluation of subtle autonomic nervous system alterations related, e.g., to drug effects.

Intracellular third loops in AT1 and AT2 receptors determine subtype specificity.

The recently cloned angiotensin II type 2 (AT2) receptor is a member of the seven transmembrane G-protein coupled receptor superfamily with a relatively low sequence homology with the angiotensin II type 1 (AT1) receptor subtype and counteracts the growth action of AT1 receptor. Intracellular third loops are known to be involved in interactions with various G proteins. We hypothesized that the intracellular third loop plays critical roles in determining the specificity of opposite functions of AT1 and AT2 receptor subtypes and examined this possibility using chimeric AT1 receptor, of which intracellular third loop is replaced with that of AT2 receptor. We transfected this chimeric receptor into PC 12 cells and observed that stimulation of this receptor inhibited extracellular signal-regulated kinase (ERK) activation and induces apoptosis, whereas the binding characteristics of this receptor remained those of ATI receptor. Taken together, these results support the notion that intracellular third loop is the critical determinant for mutually antagonistic AT1 and AT2 receptors' signaling pathways.

Why do alexithymic features appear to be stable? A 12-month follow-up study of a general population.

BACKGROUND: This 12-month follow-up study investigated the prevalence of alexithymia and its relationship with depression in a sample of the general population from Eastern Finland (n = 1,584). METHODS: Alexithymia was assessed using the 20-item version of the Toronto Alexithymia Scale (TAS) and depression using the 21-item Beck Depression Inventory (BDI). RESULTS: The prevalence of alexithymia in each study phase was similar (baseline: 9.7%; follow-up: 10.1%). Mean values of BDI, TAS-20 and subfactors of the TAS-20 also remained unchanged between the study phases. However, by using the original cutoff points, we found that a proportion of the subjects were in a different TAS-20 category on follow-up than at baseline. The mean values of BDI had not changed in those subjects who had similar alexithymia status in both phases, but increased or decreased in parallel with the change in TAS-20 score among all other subjects. CONCLUSIONS: Our findings indicate that it is important to use a variety of viewpoints when studying changes in alexithymia status. Alexithymia appears to be a stable trait based on the similarity of the mean TAS-20 scores in separate study phases. However, when focusing on the changes in alexithymia status at the individual level, alexithymic features also appear to be state dependent and strongly related to depressive symptoms.

Dynamic behavior of the auditory N100 elicited by a baby's cry.

We compared auditory N100 responses in female adults to two non-attended human sound stimuli. An infant's cry represented an unfamiliar, emotionally colored sound and the Finnish word "hei" (meaning "hi") a familiar and emotionally neutral sound. Both sounds elicited clear N100 responses over auditory areas in both hemispheres. However, the dynamic behavior of the N100 response following the first few repetitions of the sounds was significantly different. We observed faster habituation and longer response latencies, particularly over the ipsilateral hemisphere, during the first and second repetitions of the cry stimulus. This pattern may reflect an altered arousal level and slower, bilateral processing during the unfamiliar emotionally loaded cry as compared to the emotionally neutral word "hei" .