Unnatural-cause mortality patterns of Northern Finnish men and women diverge in adolescence – A 52-year follow-up

The Finnish population has a long life expectancy but ranks high in unnatural deaths on the European scale. Mortality has historical regional discrepancy in Finland, as Northern Finns are overrepresented in both natural and unnatural deaths. This study aimed to characterize the age- and sex-related trends in unnatural mortality among Northern Finns. Altogether 12 143 individuals, constituting >95% of births in Northern Finland in 1966, were followed up for a median of 52 years. The mortality patterns of this population were studied using death record data. Crude annual mortality rates were calculated and graphed for 10-year age strata (all-cause, natural-cause, and unnatural-cause mortality, as well as accident, suicide, and homicide mortality). Cox regression was used to analyze the sex discrepancy in mortality. A total of 874 deaths (7.2%) occurred during the follow-up period. Women had 47% and 73% lower risks of any death and unnatural death than men, respectively. From the second decade of life onwards, the unnatural mortality of men was 3–5 times that of women. Accident and suicide mortality rates of men were 2–13 and 2–3 times those of women, respectively. Homicides were rare among either sex. We conclude that Northern Finnish women have a substantially lower risk of all-cause mortality and unnatural mortality than men. To aid the development of preventive strategies, future studies should aim to identify the underlying factors behind unnatural mortality. Primarily, emphasis should be placed on the increased mortality of men from the second decade of life onwards.Peer reviewe

Autopsy-Based Learning is Essential But Underutilized in Medical Education: A Questionnaire Study

To this day, autopsies and dissections have been essential in medical education, but declining autopsy numbers have endangered this long-standing tradition. Students' perceptions of these teaching methods should be constantly updated to help educators understand how to achieve their teaching goals. The purpose of this study was to explore the state of autopsy- and dissection-based teaching in two Finnish universities based on the experiences of the students, survey their perceptions of such teaching, and to compare the Finnish situation with students' perceptions in other countries as it emerges from medical literature. A questionnaire went to 859 second-, fourth-, and sixth-year medical students. The questions concerned dissection and autopsy classes these students had attended, the views of the students in regard to the number of classes, and the benefits of and attitudes towards autopsy teaching. An open question of how to improve autopsy teaching was included. The response rate was 19.4%. Most respondents requested more autopsy and dissection classes, especially practical education. They found autopsies most beneficial in learning anatomy and dealing with one's own emotions related to death. Their experiences proved least beneficial for interaction with the relatives of a deceased patient and for people skills. Integrational methods and focusing on the main learning outcomes were suggested as improvements. Overall, students found dissection and autopsy teaching important, but felt concerned about the diminishing autopsy numbers. Focusing on main learning objectives and better integration of autopsies in the teaching of different specialties could help to utilize autopsies to a greater extent

MiR-185-5p regulates the development of myocardial fibrosis

Background: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis. Methods and results: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-beta 1 and collagen I. Conclusions: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.Peer reviewe

Thrombomodulin and catecholamines as post-mortem indicators of hypothermia

Abstract Hypothermia deaths pose a difficult challenge from the medico-legal point of view because no specific traces are left on the cadaver to be examined post-mortem. The concentrations of urinary catecholamines, adrenaline and noradrenaline increase in various stressful situations including cold stress, and high levels have been considered to be suggestive of lethal hypothermia. There is, however, a need for a better hypothermia indicator. A potential candidate could be thrombomodulin (TM), an endothelially expressed protein whose plasma concentration has been shown to elevate in response to hypothermia. TM and catecholamine levels were studied in short-term cold exposure (human subjects, n = 7), in mild and severe hypothermia with or without rewarming (rats, n = 96) and in hypothermia deaths compared with deaths from cardiovascular diseases, traumas and other causes (autopsy cases, total n = 552). Myocardial thrombomodulin transcript expression was increased in severely hypothermic rats, but was lower in hypothermia deaths than in other causes. The circulating TM level was transiently reduced in severe hypothermia. The myocardial and urinary TM protein levels were reduced in lethal hypothermia compared with other causes of death. TM and catecholamine levels correlated significantly in blood and urine both in living subjects and post-mortem examination. In severely hypothermic rats, there was an inverse relationship between plasma adrenaline concentration and myocardial thrombomodulin transcript level. The results suggest that TM expression and secretion are altered by hypothermia, possibly linked to the actions of catecholamines. Analysing the post-mortem catecholamine and TM levels provides evidence of ante-mortem cold stress in suspected hypothermia deaths. Further studies should be conducted in order to reveal the exact mechanisms behind the regulation of TM on cell level.Tiivistelmä Paleltumiskuolemat ovat oikeuslääketieteellisesti haastavia, koska vainajaan ei jää paleltumiseen viittaavia yksiselitteisiä löydöksiä. Virtsan katekoliamiinien, adrenaliinin ja noradrenaliinin, pitoisuudet kasvavat stressitilanteissa kuten kylmäaltistuksessa. Korkeita pitoisuuksia on pidetty paleltumiseen viittaavana tekijänä. Paremmalle paleltumista osoittavalle merkkiaineelle on kuitenkin selkeä tarve. Eräs mahdollinen merkkiaine voisi olla trombomoduliini (TM), joka on endoteelisolujen tuottama proteiini. Sen plasmapitoisuuden on aiemmin osoitettu nousevan alilämpöisyystilassa. TM- ja katekoliamiinitasoja tutkittiin lyhyessä kylmäaltistuksessa (koehenkilöt, n = 7) sekä lievässä ja vaikeassa alilämpöisyystilassa joko lämmityksen jälkeen tai ilman lämmitystä (rotat, n = 96). Lisäksi verrattiin paleltumisen, sydän- ja verisuonitautien, vammojen sekä muiden syiden aiheuttamia kuolemia (ruumiinavausaineisto, n = 552). Sydänlihaksen trombomoduliini-transkriptin taso oli kohonnut vaikeasti alilämpöisillä rotilla, mutta se oli matalampi paleltumiskuolemissa kuin muissa kuolemissa. Veren TM-taso oli hetkellisesti alentunut vaikeassa alilämpöisyystilassa. Sydänlihaksen ja virtsan TM-proteiinipitoisuudet olivat matalampia paleltumiskuolemissa kuin muissa kuolemansyissä. TM- ja katekoliamiinitasot korreloivat merkittävästi veressä ja virtsassa sekä koehenkilöillä ja -eläimillä että vainaja-aineistossa. Vaikeasti alilämpöisillä rotilla todettiin käänteinen suhde plasman adrenaliinipitoisuuden ja sydänlihaksen trombomoduliini-transkriptitason välillä. Tulosten perusteella alilämpöisyystila muuttaa TM:n ekspressiota ja erittymistä, mikä voi liittyä katekoliamiinien vaikutuksiin. Kuolemanjälkeisten TM- ja katekoliamiinitasojen määritys tuo lisänäyttöä kuolemaa edeltäneestä kylmävaikutuksesta epäiltäessä paleltumiskuolemaa. Lisätutkimuksia tarvitaan TM:n solutason säätelymekanismien selvittämiseksi