"Mapping suicide prevention initiatives targeting Indigenous Sámi in Nordic countries".

BACKGROUND: Suicide is a major public health issue among Indigenous Sámi in Nordic countries, and efforts to prevent suicide in the Sámi context are increasing. However, there is no literature on suicide prevention initiatives among Sámi. The aim of the study was to map suicide prevention initiatives targeting Sámi in Norway, Sweden, and Finland during 2005-2019. METHOD: Initiatives were identified and described through utilizing networks among stakeholders in the field of suicide prevention among Sámi, acquiring documentation of initiatives and utilizing the authors first-hand experiences. The described initiatives were analyzed inspired by the "What is the problem represented to be?" (WPR)-approach. RESULTS: Seventeen initiatives targeting Sámi were identified during 2005-2019, including nine in Sweden, five in Norway, one in Finland and two international initiatives. Analysis with the WPR-approach yielded 40 problematizations regarding how to prevent suicide among Sámi, pertaining to shortcomings on individual (5), relational (15), community/cultural (3), societal (14) and health systems levels (3). All initiatives were adapted to the Sámi context, varying from tailor-made, culture-specific approaches to targeting Sámi with universal approaches. The most common approaches were the gatekeeper and mental health literacy training programs. The initiatives generally lacked thorough evaluation components. CONCLUSION: We argue that the dominant rationales for suicide prevention were addressing shortcomings on individual and relational levels, and raising awareness in the general public. This threatens obscuring other, critical, approaches, such as broadening perspectives in prevention planning, improving health systems for Sámi, and promoting cultural empowerment among Sámi. Nevertheless, the study confirms considerable efforts have been invested into suicide prevention among Sámi during the last 15 years, and future initiatives might include a broader set of prevention rationales. To improve evaluation and identify the most promising practices, increased support regarding development of plans and implementation of evaluation components is needed.

Population resequencing of European mitochondrial genomes highlights sex-bias in Bronze Age demographic expansions.

Interpretations of genetic data concerning the prehistory of Europe have long been a subject of great debate, but increasing amounts of ancient and modern DNA data are now providing new and more informative evidence. Y-chromosome resequencing studies in Europe have highlighted the prevalence of recent expansions of male lineages, and focused interest on the Bronze Age as a period of cultural and demographic change. These findings contrast with phylogeographic studies based on mitochondrial DNA (mtDNA), which have been interpreted as supporting expansions from glacial refugia. Here we have undertaken a population-based resequencing of complete mitochondrial genomes in Europe and the Middle East, in 340 samples from 17 populations for which Y-chromosome sequence data are also available. Demographic reconstructions show no signal of Bronze Age expansion, but evidence of Paleolithic expansions in all populations except the Saami, and with an absence of detectable geographical pattern. In agreement with previous inference from modern and ancient DNA data, the unbiased comparison between the mtDNA and Y-chromosome population datasets emphasizes the sex-biased nature of recent demographic transitions in Europe.

Seasonal variation in affective and other clinical symptoms among high-risk families for bipolar disorders in an Arctic population.

BACKGROUND: In bipolar disorder (BD), seasonality of symptoms is common and disturbances in circadian rhythms have been reported. OBJECTIVES: We identified high-penetrance families in a geographically restricted area in Northern Fennoscandia and studied the seasonal variation of clinical symptoms among BD subjects and their healthy relatives. DESIGN: We explored the clinical characteristics of subjects living in Northern Fennoscandia, with extreme annual variation in daylight. Among known indigenous high-risk families for BD, we compared the affected ones (N=16) with their healthy relatives (N=15), and also included 18 healthy non-related controls from the same geographical area. Seasonal fluctuation in clinical measures was followed up at the 4 most demarcated photoperiodic time points of the annual cycle: around the summer solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder Questionnaire (MDQ)] and morningness-eveningness questionnaire type (MEQ) were registered, whereas in the follow-up, depressive [Beck Depression Inventory (BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol consumption and sleep were recorded. RESULTS: Possibly indicative or statistically significant differences in symptoms between the affected subjects and their healthy relatives were the BDI winter (13.3 vs. 2.6, t=-2.51, p=0.022) and spring scores (12.6 vs. 3.2, t=-1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=-2.08, p=0.052) and spring scores (3.8 vs. 0.82, t=-1.97, p=0.063). Scores were higher among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3) at all the time points, and without the notable seasonality which was observed among the healthy relatives. In the overall population, MDQ and MEQ scores had an inverse correlation (-0.384, significant at 0.016), indicating increased lifetime manic behaviour among "the night owl" chronotype subjects. CONCLUSIONS: In an Arctic population sample, we found different seasonal fluctuation in mood and distress symptoms and sleep duration scores between subjects with bipolar spectrum disorders and their healthy relatives. Despite the relatively small sample size, the results indicate that the symptoms and signs of BD relate to a disturbance in seasonal variation. Seasonal variation can be considered as an interesting endophenotype for BD and a promising target for further genetic studies.

Large-scale recent expansion of European patrilineages shown by population resequencing.

The proportion of Europeans descending from Neolithic farmers ∼ 10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ∼ 2.1-4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes.

Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis.

Changes in the collagenous matrix may contribute to the pathogenesis and progression of human aortic valve stenosis (AS). To evaluate the significance of collagen I and III in the pathogenesis of AS, we studied their synthesis in diseased valves. Type I and type III collagen mRNA expression and the immunohistochemical localization of the collagen antigens were studied from 36 AS and 2 normal aortic valves. The concentrations of propeptides and telopeptide structure of type I (PINP, PICP, and ICTP) and those of III collagens (PIIINP and IIINTP) were measured by radioimmunoassays in soluble tissue extracts and trypsin-solubilized calcified and non-calcified matrices of 11 AS and 24 healthy aortic valves of different ages. The synthesis of type I collagen, localized in the myofibroblasts adjacent to calcified nodules, was two- to three-fold in the AS samples compared to the controls. The proportion of collagen in the total protein fraction was 90% in the healthy valves, 50% in the non-calcified matrix, and 10% in the calcified matrix of AS valves. In the calcified valves, the ICTP content was six-fold compared to the age-matched controls and two-fold compared to the young control group. In the controls, the amount of ICTP in type I collagen decreased with age (r=-0.908, p<0.001) and was replaced by other cross-linked C-telopeptide structure. The concentration of type III collagen decreased during aging (r=-0.753, p<0.001). The decrease in total collagen content, despite the increase in type I collagen synthesis indicates an increase in collagen turnover in AS. The calcification of the aortic valves is accompanied by increased amount of ICTP in type I collagen.

Differently cross-linked and uncross-linked carboxy-terminal telopeptides of type I collagen in human mineralised bone.

In bone matrix, type I collagen is stabilised by covalent cross-links formed between adjacent collagen molecules; the majority of which is believed to be immature, divalent bonds. For studying these immature forms in detail, we have developed an immunoassay for a synthetic peptide SP 4 that is analogous with and detects a linear epitope within the C-telopeptide of alpha1-chain of type I collagen. The SP 4 assay, together with the ICTP assay, which is specific for the trivalently cross-linked C-telopeptide, was used for the isolation of the differently cross-linked C-telopeptide structures of the alpha1-chain of type I collagen present in mineralised human bone. Amino acid analysis, peptide sequencing and MALDI-TOF mass spectrometry were used to identify and characterise each of the isolated structures. The cross-link content of each isolated peptide was identified. In the trivalent ICTP peptide, only 40% was cross-linked with pyridinoline, the remainder of the cross-links being currently uncharacterized. The divalent peptides contained only previously characterised cross-linking structures. Most of the divalent cross-links were dihydroxylysinonorleucine (DHLNL), with minor amounts of hydroxylysinonorleucine (HLNL). The relative proportion of the HLNL cross-link was slightly higher in the divalent alpha1Calpha2H peptide. A substantial amount of uncross-linked telopeptide structures was also found. Previous studies, where direct chemical cross-link analyses have been used to assess the maturity of cross-linking, have inferred that bone contains more divalently than trivalently cross-linked C-telopeptides. The immunochemical peptide approach used in this study may help to detect presently uncharacterized, trivalent cross-links, the presence of which is strongly suggested in this study. It also provides additional information regarding the extent and maturity of tissue type I collagen cross-linking in health and disease.

Increased content of type III collagen at the rupture site of human Achilles tendon.

We compared the type I and III collagen amounts and cross-linked telopeptides at the rupture site and two other sites of the same tendon. Tendon samples of ten individuals with total Achilles tendon rupture and six healthy cadavers were collected. The newly synthesized type I and III procollagens were assessed by extracting the soluble propeptides PINP, PICP and PIIINP. The insoluble matrix was solubilized by heat denaturation and trypsin digestion. Hydroxyproline, the cross-linked telopeptide structures of type I (ICTP and SP 4) and III collagens (IIINTP) and the degradation product of type III collagen (tryptic PIIINP) were measured from the digests. The type III collagen content was significantly increased at the rupture site when compared to control sites (5- and 12-fold increased) or cadavers (5-fold increased). No changes in the amounts of newly synthesized type I and III procollagens were observed. The ICTP content decreased and the SP 4/ICTP ratio increased along with ageing, suggesting a structural change in the type of cross-link in the carboxyterminal telopeptide of type I collagen. Type III collagen has accumulated at the rupture site probably due to microtraumas and the subsequent healing process. The increased content of type III collagen can cause thinner collagen fibers, decrease the tensile strength and may finally result in total rupture of the tendon. The age-related change in the nature of the cross-link in the carboxyterminal telopeptide may contribute to this weakening.