MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis

Rationale: Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs and their usefulness as therapeutic targets in this process are unknown. Objective: To identify microRNAs involved in viral myocarditis pathogenesis and susceptibility. Methods and Results: Cardiac microRNAs were profiled in both human myocarditis and in Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses diverged depending on the susceptibility to myocarditis after viral infection in mice. MicroRNA-155, -146b, and -21 were consistently and strongly upregulated during acute myocarditis in both humans and susceptible mice. We found that microRNA-155 expression during myocarditis was localized primarily in infiltrating macrophages and T lymphocytes. Inhibition of microRNA-155 by a systemically delivered LNA-anti-miR attenuated cardiac infiltration by monocyte-macrophages, decreased T lymphocyte activation, and reduced myocardial damage during acute myocarditis in mice. These changes were accompanied by the derepression of the direct microRNA-155 target PU.1 in cardiac inflammatory cells. Beyond the acute phase, microRNA-155 inhibition reduced mortality and improved cardiac function during 7 weeks of follow-up. Conclusions: Our data show that cardiac microRNA dysregulation is a characteristic of both human and mouse viral myocarditis. The inflammatory microRNA-155 is upregulated during acute myocarditis, contributes to the adverse inflammatory response to viral infection of the heart, and is a potential therapeutic target for viral myocarditis.     

Growth hormone and cortisol in serum and saliva

Salivary diagnosis is a developing area in clinical chemistry and dentistry. Cortisol analyses from saliva have been used in pediatric practice and as doping tests. Growth hormone (hGH), also a stress hormone, has not been analyzed from saliva. We studied the serum and saliva of 51 healthy subjects. The samples were taken at 8:00 in the morning after 12 h fasting. Cortisol concentrations were analyzed using RIA. An immunoradiometric assay was applied for analyzing serum and salivary hGH. The validity of this method developed in our laboratory was found to be good. The results showed correlation of salivary cortisol with that of serum (r = 0.47, P < 0.001). Salivary hGH concentrations were 1000-fold lower than the respective values in serum, but a clear correlation was found between salivary and serum hGH levels (r = 0.59, P < 0.001).     

Dental fear and oral health and family characteristics of Finnish children

Objectives: Our aim was to describe the occurrence of dental fear among Finnish children of different ages and to ascertain how oral health and family characteristics are associated with dental fear. Methods: The subject groups were aged 3, 6, 9, 12, and 15 years in two middle‐sized cities, and the 1474 participants were distributed over fairly equal samples of each age. A questionnaire given to each child to be filled out at home enquired about social background, oral hygiene habits, diet, and dental fear. Oral health status was examined clinically and radiographically by two calibrated dentists. Multiple logistic regression analyses were performed for each age group in order to study the associations between dental fear and selected factors. Results: Dental fear was higher among 12‐ and 15‐year‐old children than among the younger ones. Pain, drilling, and local anesthesia were reported to be the most frightening aspects. Excluding the 12‐year‐olds, children whose family members reported dental fear were more likely to report dental fear than children whose family members did not report dental fear. Six‐ and 12‐year‐olds who had experienced caries were more likely to report dental fear than were caries‐free children. Among 6‐year‐olds, father's education modified the effect of a child's caries experience on child dental fear. Frequent intake of sugary items and a limit on eating candies to only one day per week were associated with higher dental fear. Conclusions: Fear of dental treatment is still fairly common among Finnish children, and the factors associated with it differ with the age of the child.     

THE EFFECTS OF HYPNOSIS AND HYPNOTIC SUGGESTIONS ON THE MISMATCH NEGATIVITY IN HIGHLY HYPNOTIZABLE SUBJECTS

The neural mechanisms associated with hypnosis were investigated in a group of 9 high hypnotizable subjects by measuring the mismatch negativity (MMN) component of the auditory event-related potential (ERP). ERPs were recorded using a passive oddball paradigm to sinusoidal standard and deviant tone stimuli of 500 and 520 Hz, respectively, in four conditions: prehypnosis, neutral hypnosis, hypnotic suggestion for altering the tone perception, and posthypnotic conditions. Earlier studies have indicated that hypnosis and hypnotic suggestions might have an effect on MMN, but the results of our study contradict these results: No statistically significant differences were found between the conditions in the MMN amplitudes.     

Chromosome abnormalities in peripheral T-cell lymphoma

We have studied neoplastic lymph nodes from six patients histologically, immunologically and cytogenetically. Histologically all the cases were classified as peripheral T-cell lymphomas. These were subclassified as T-zone lymphomas in three, large cell 'pale cell' variant in one, large cell immunoblastic in one, and small cell, mycosis fungoides in one. Two had features of angioimmunoblastic lymphadenopathy (AILD). Immunologically all cases expressed CD2 (OKT11) and CD4 (T4). All six cases had clonal chromosome abnormalities, although in four cases the majority of cells were chromosomally normal. Chromosome 3 was most often involved in abnormalities, occurring in five patients. The most common single chromosome abnormality, trisomy 3, was seen in all three cases classified as T-zone lymphoma and in no other cases. In the two cases with features of AILD only numerical abnormalities were seen, whereas in the other cases complicated structural rearrangements were present. Recurring structural abnormalities involved bands 1p12or13, 1q32, 3p25 and 14q11. Our data suggest that cytogenetic analysis may assist in diagnosis and classification of the peripheral T-cell lymphomas.     

Lowered vision as a risk factor for injurious accidents in older people

BACKGROUND AND AIMS: Poor vision in older people is often related to increased fall risk. However, the association of the severity between visual deficit and risk for all kind of injurious accidents has not been widely studied. The aim of this study was to examine whether visual loss is associated with higher incidence of injurious accidents and whether walking speed or physical activity play a mediating role in the association. METHODS: 416 persons aged 75 and 80 years at baseline underwent visual acuity measurements. Visual acuity (VA) <0.3 in the better eye, with spectacle correction when necessary, was defined as visual impairment, VA >or=0.3 but 0.5 as normal VA. Hospital records of accidents resulting in injury were monitored for 10 years after baseline. RESULTS: During the 10-year follow-up, 239 (58%) participants suffered at least one injurious accident. The risk for injurious accidents in a multivariate model adjusted for age, gender, eye-related diseases, diabetes and cardiovascular diseases among participants with lowered vision was 1.45 (95% CI 1.08- 1.94), compared with that for people with normal visual acuity. Participants with visual impairment did not have an increased risk for injurious accidents (HR 1.20, 95% CI 0.82-1.75). Furthermore, neither walking speed nor physical activity had a mediating effect on the relationship between visual loss and accidents. CONCLUSIONS: Lowered vision is a risk factor for injurious accidents in older people independent of mobility and physical activity. Interestingly, more severe visual impairment did not increase the risk. Early intervention strategies, for example, proper correction of refractive errors or cataract extraction, may potentially prevent injurious accidents in older people.     

Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.     

Background factors of molar-incisor hypomineralization in a group of Finnish children

Objective. Molar-Incisor Hypomineralization (MIH) is a common developmental enamel defect characterized by demarcated opacities in permanent molars and incisors. Its etiology still remains unclear. The aim of this retrospective cohort study was to assess if the socioeconomic environment of the child is associated with MIH. Materials and methods. The study was located in two rural towns and three urban cities in Finland. A total of 818 children, between 7–13 years old, were examined for MIH using the evaluation criteria in line with those of the European Academy of Paediatric Dentistry, but excluding opacities smaller than 2 mm in diameter. The mothers filled in a questionnaire which included questions related to the family’s way of living (e.g. area of residency, farming, day care attendance) and socioeconomic status (family income, number of mother’s school years, level of maternal education). Results. The prevalence of MIH in the study population was 17.1%. Family income, urban residency and day care attendance were associated with MIH in the univariate analysis. In the multivariate analysis using binary logistic regression, only urban residency during a child’s first 2 years of life remained associated with MIH. The prevalence of MIH in urban areas was 21.3% and in rural areas 11.5% (OR = 2.18, CI = 1.35–3.53, p = 0.001). Conclusions. The prevalence of MIH was related to urban residency and could not be explained by any other factor included in the study.