Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development

p53 is a key component of a signaling network that protects cells against various stresses. As excess p53 is detrimental to cells, its levels are tightly controlled by several mechanisms. The E3 ubiquitin ligase Mdm2 is a major negative regulator of p53. The significance of balanced p53 levels in normal tissues, at different stages of lifetime, is poorly understood. We have studied in vivo how the disruption of Mdm2/p53 interaction affects the early-embryonic otic progenitor cells and their descendants, the auditory supporting cells and hair cells. We found that p53 accumulation, as a consequence of Mdm2 abrogation, is lethal to both proliferative progenitors and non-proliferating, differentiating cells. The sensitivity of postmitotic supporting cells to excess p53 decreases along maturation, suggesting that maturation-related mechanisms limit p53's transcriptional activity towards pro-apoptotic factors. We have also investigated in vitro whether p53 restricts supporting cell's regenerative capacity. Unlike in several other regenerative cellular models, p53 inactivation did not alter supporting cell's proliferative quiescence nor transdifferentiation capacity. Altogether, the postmitotic status of developing hair cells and supporting cells does not confer protection against the detrimental effects of p53 upregulation. These findings might be linked to auditory disturbances observed in developmental syndromes with inappropriate p53 upregulation.Peer reviewe

Behaviour management problems in Finnish children with operated congenital heart disease : a practice-based study

Purpose This retrospective, practice-based study investigates behaviour management problems (BMPs) in dental care among Finnish children with operated congenital heart disease (CHD). Methods All the heart-operated children born between the years 1997 and 1999 were identified in the national ProCardio database (n = 570). Primary dental care records were requested from this population and were eventually received from 211 patients. Information on gender, diagnosis, number of heart operations and perioperative care were collected from the ProCardio database, and the CHDs were categorised as shunting/stenotic/complex/other defects. Data on BMP/dental fear, oral conscious sedation, dental general anaesthesia (DGA) and past and present caries indices at 6, 12 and 15 years (d/D, dmft/DMFT) were assessed. Results Notes on behaviour management problems or dental fear were found in 19% of the study population. BMPs in dental care were more frequent among boys. Children with re-operations, longer post-operative intensive care stay and hospitalisation, and complications had not more BMP than others. Those children diagnosed with syndromes had more BMP often than the rest. Past and present caries experience were significantly associated with BMP, need of oral conscious sedation and DGA. Oral conscious sedation, nitrogen oxide sedation and dental general anaesthesia were used in 17/211, 2/221 and 24/211 CHD patients, respectively. Conclusion Dental caries remains a main factor associated with BMP in the CHD population. Need for oral conscious sedation and DGA were rather common. To maintain a good oral health and to avoid development of BMP, CHD children benefit from focus in health promotion and preventive care.Peer reviewe

Dental caries and attendance to dental care in Finnish children with operated congenital heart disease. A practice based follow-up study

Purpose Oral health of children with congenital heart disease (CHD) is of utmost importance. This study aimed to investigate the prevalence of dental caries and attendance to dental care in Finnish heart-operated CHD patients born in 1997-1999. Methods The cohort of children born in 1997-1999 was selected using a national register on all heart-operated children in Finland. Gender, general health problems, diagnosis, type of the heart defect (shunting, stenotic and complex defects), and number of operations were available and included in the analyses. Dental records from primary health care were collected from municipalities with their permission. The data comprised of the number of dental examinations and data on caries status (dt, DT, dmft, DMFT) at the age of 7 (grade 1), 11 (grade 5) and 15 (grade 8) years and at the most recent examination. The control group consisted of dental data on patients born in 1997-1999 provided by the City of Oulu, Finland (n = 3356). Results Oral patient records of 215/570 children were obtained. The difference between the defect types was statistically significant both for DT (p = 0.046) and DMFT (p = 0.009) at the age of 15 (grade 8). The prevalence of caries did not differ between the study population and the controls. High present and past caries experiences were not associated with higher number of visits to oral health care, especially to oral hygienist, or with oral health promotion. National obligations concerning dental visits were not implemented in all municipalities. Conclusion There seems to be a need for oral health promotion and preventive means implemented by oral hygienists among those with CHD.Peer reviewe

Outcome of Chair-Side Dental Fear Treatment: Long-Term Follow-Up in Public Health Setting

Aim. Purpose of this practice and data-based study was to evaluate the outcome of dental fear treatment of patients referred to the Clinic for Fearful Dental Patients (CFDP) in the primary oral health care, City of Oulu, Finland, during period 2000-2005. Methods. A psychological approach including behavioral interventions and cognitive behavioral therapy (BT/CBT) was used for all participants combined with conscious sedation or dental general anesthesia (DGA), if needed. The outcome was considered successful if later dental visits were carried out without any notifications in the patient records of behavioral problems or sedation. Data collection was made in 2006; the average length of the observation period from the last visit in the CFPD to data collection was 2y 3m (SD 1y 5m). All information was available for 163 patients (mean age 8.9y at referral). Study population was dominated by males (58.0%). Cause for referrals was mostly dental fear (81.0%) or lack of cooperation. Results. The success rate was 69.6% among females and 68.1% among males. Success seemed to be (p=0.053) higher for those treated in 12years compared with the older ones. The participants, without need for dental general anesthesia (DGA) in the CFDP, had significantly a higher success rate (81.4%) compared with those who did (54.8%, p<0.001). Use of conscious oral sedation (p=0.300) or N2O (p=0.585) was not associated with the future success. Conclusions. A chair-side approach seems successful in a primary health care setting for treating dental fear, especially in early childhood. Use of sedation seems not to improve the success rate

Macromolecular and electrical coupling between inner hair cells in the rodent cochlea

Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding

Cutting productivity of windfalls in Finland

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Electrocardiogram as a predictor of sudden cardiac death in middle-aged subjects without a known cardiac disease

Background: Abnormal 12 lead electrocardiogram (ECG) findings and proposing its ability for enhanced risk prediction, majority of the studies have been carried out with elderly populations with prior cardiovascular diseases. This study aims to denote the association of sudden cardiac death (SCD) and various abnormal ECG morphologies using middle-aged population without a known cardiac disease. Methods: In total, 9511 middle-aged subjects (mean age 42 +/- 8.2 years, 52% males) without a known cardiac disease were included in this study. Risk for SCD was assessed after 10 and 30-years of follow-up. Results: Abnormal ECG was present in 16.3% (N = 1548) of subjects. The incidence of SCD was distinctly higher among those with any ECG abnormality in 10 and 30-year follow-ups (1.7/1000 years vs. 0.6/1000 years, P 100', left ventricular hypertrophy, and T-wave inversions were the most significant independent ECG risk markers for 10-year SCD prediction with up to 3-fold risk for SCD. Those with ECG abnormalities had a 1.3-fold risk (95% CI 1.07-1.57, P - 0.007) for SCD in 30-year follow-up, whereas QRST-angle > 100 degrees, LVH, ER 0.1 mV and 0.2 mV were the strongest individual predictors. Subjects with multiple ECG abnormalities had up to 6.6-fold risk for SCD (P <0.001). Conclusion: Several ECG abnormalities are associated with the occurrence of early and late SCD events in the middle-age subjects without known history of cardiac disease. (C) 2018 The Authors. Published by Elsevier B.V.Peer reviewe

Negotiating care in the context of Finnish and Italian elder care policies

Negotiation is an integral part of all elder care, which by definition involves a relation between at least two people. In this article we analyse negotiations concerning elder care in the context of Finnish and Italian elder care policies. At the macro level negotiations on elder care are shaped by elder care policies and at the micro level by individual skills and resources. Our focus is on the negotiations on eligibility that take place when elders attempt to access care. The data consist of qualitative interviews with Finnish and Italian elders in need of care. The analysis of individual experiences of care negotiations reflects the implementation of elder care policies. The results indicate that the most negotiated eligibility criteria when seeking access to elder care are need, money and social relations. These criteria are negotiated when seeking eligibility to different sources of care: informal care, grey market, market-based, non-profit and public services. In Italy, negotiation is particularly crucial when accessing grey market care. Cash as the main Italian elder care policy tool tends to enhance the role of and need for negotiation. In Finland, a greater part of elder care is provided by the public sector and therefore the process of negotiation is more standardized than in Italy

Electrocardiographic Risk Markers of Cardiac Death : Gender Differences in the General Population

Background Cardiac death is one of the leading causes of death and sudden cardiac death (SCD) is estimated to cause approximately 50% of cardiac deaths. Men have a higher cardiac mortality than women. Consequently, the mechanisms and risk markers of cardiac mortality are not as well defined in women as they are in men. Aim The aim of the study was to assess the prognostic value and possible gender differences of SCD risk markers of standard 12-lead electrocardiogram in three large general population samples. Methods The standard 12-lead electrocardiographic (ECG) markers were analyzed from three different Finnish general population samples including total of 20,310 subjects (49.9% women, mean age 44.8 +/- 8.7 years). The primary endpoint was cardiac death, and SCD and all-cause mortality were secondary endpoints. The interaction effect between women and men was assessed for each ECG variable. Results During the follow-up (7.7 +/- 1.2 years), a total of 883 deaths occurred (24.5% women, p 110 ms (p = 490 ms and T-wave inversions predicted SCD (p <0.047 and 0.033, respectively). In the interaction analysis, LVH (HR: 2.4; 95% CI: 1.2-4.9; p = 0.014) was stronger predictor of primary endpoint in women than in men. Conclusion Several standard ECG variables provide independent information on the risk of cardiac mortality in men but not in women. LVH and T-wave inversions predict SCD also in women.Peer reviewe