Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Complications after pediatric percutaneous endoscopic gastrostomy: comparison of the push and pull technique.

Purpose: Various complications are associated with percutaneous endoscopic gastrostomy (PEG) procedures in children. The push technique is being increasingly used, but its complications are insufficiently characterized. We aimed to assess all complications related to PEG procedures and compare the safety of the pull and push techniques. Methods: Retrospective review of consecutive pediatric patients who underwent PEG between 2002 and 2020. Results: In total, 216 children underwent 217 PEG procedures. The push technique was used in 138 (64%) cases, and the pull technique in 79 (36%) cases. The median follow-up time was 6.1 (0.1-18.3) years. The complication rate was high (57%) and patients experienced complications years after the procedure. Overall, 51% and 67% of patients experienced complications in the push and pull groups, respectively. The rates of minor and major complications were higher in the pull group than in the push group (63% vs 48%, p=0.028; and 11% vs 6%, p=0.140, respectively). Reoperation was also more common in the pull group (17% vs 7%, p=0.020). Conclusions: The overall complication rate of PEG procedures is high. Fortunately, most complications are mild and do not require reoperations. The increasing push technique appears to be safer than the traditional pull technique. Significant long-term morbidity is related to gastrostomies in children.

Mental health service diversity and work disability: associations of mental health service system characteristics and mood disorder disability pensioning in Finland.

PURPOSE: Public mental health services (MHS) are crucial in preventing psychiatric disability pensions (DP). We studied the associations between mood disorder DP risk and the characteristics of Finnish municipalities' MHS provision using the ESMS-R mapping tool and Finnish population registers, based on first-time granted mood disorder DPs between 2010 and 2015. METHODS: The final data set included 13,783 first-time mood disorder DP recipients and 1088 mental health service units in 104 municipalities. We focused on five different MHS types: all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. Three factors for each MHS type were studied: service resources, richness, and diversity index. Negative binomial regression models were used in the analysis. RESULTS: In all the municipalities, higher service richness and diversity regarding all MHS, outpatient care and local services with gatekeeping were associated with a lower DP risk. In urban municipalities, service richness was mainly associated with lower DP risk, and in semi-urban municipalities service diversity and resources were primarily associated with lower DP risk in outpatient care and local services with gatekeeping. In rural municipalities, DP risk indicated no association with MHS factors. CONCLUSION: The organization and structure of MHS play a role in psychiatric disability pensioning. MHS richness and diversity are associated with lower mood disorder DP in specific societal contexts indicating their role as quality indicators for regional MHS. The diversity of service provision should be accounted for in MHS planning to offer services matching population needs.

Tensorial Principal Component Analysis in Detecting Temporal Trajectories of Purchase Patterns in Loyalty Card Data: Retrospective Cohort Study.

BACKGROUND: Loyalty card data automatically collected by retailers provide an excellent source for evaluating health-related purchase behavior of customers. The data comprise information on every grocery purchase, including expenditures on product groups and the time of purchase for each customer. Such data where customers have an expenditure value for every product group for each time can be formulated as 3D tensorial data. OBJECTIVE: This study aimed to use the modern tensorial principal component analysis (PCA) method to uncover the characteristics of health-related purchase patterns from loyalty card data. Another aim was to identify card holders with distinct purchase patterns. We also considered the interpretation, advantages, and challenges of tensorial PCA compared with standard PCA. METHODS: Loyalty card program members from the largest retailer in Finland were invited to participate in this study. Our LoCard data consist of the purchases of 7251 card holders who consented to the use of their data from the year 2016. The purchases were reclassified into 55 product groups and aggregated across 52 weeks. The data were then analyzed using tensorial PCA, allowing us to effectively reduce the time and product group-wise dimensions simultaneously. The augmentation method was used for selecting the suitable number of principal components for the analysis. RESULTS: Using tensorial PCA, we were able to systematically search for typical food purchasing patterns across time and product groups as well as detect different purchasing behaviors across groups of card holders. For example, we identified customers who purchased large amounts of meat products and separated them further into groups based on time profiles, that is, customers whose purchases of meat remained stable, increased, or decreased throughout the year or varied between seasons of the year. CONCLUSIONS: Using tensorial PCA, we can effectively examine customers' purchasing behavior in more detail than with traditional methods because it can handle time and product group dimensions simultaneously. When interpreting the results, both time and product dimensions must be considered. In further analyses, these time and product groups can be directly associated with additional consumer characteristics such as socioeconomic and demographic predictors of dietary patterns. In addition, they can be linked to external factors that impact grocery purchases such as inflation and unexpected pandemics. This enables us to identify what types of people have specific purchasing patterns, which can help in the development of ways in which consumers can be steered toward making healthier food choices.

Patterns of mental health services and mood disorder disability pensions: a standard comparison of Finland's three largest hospital districts.

INTRODUCTION: Mental disorders are one of the most common and disabling health conditions worldwide. There is however no consensus on the best practice of system level mental health services (MHS) provision, in order to prevent e.g. mood disorder disability pensions (DPs). We analyzed the MHS provision between Finland's three largest hospital districts Helsinki and Uusimaa (HUS), Southwest Finland and Pirkanmaa, with known differences in mood disorder DP risk but presumably equal rates of mood disorder prevalence. METHODS: We used public MHS data analyzed with the standardized DEscription and Evaluation of Services and DirectoriEs for Long Term Care (DESDE-LTC) mapping tool, focusing on all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. We also collected demographic data based on the European Socio-Demographic Schedule (ESDS). As a novel approach, the Gini-Simpson Diversity Index (GSDI) was calculated for the districts. RESULTS: Evident differences were observed regarding the districts' MHS factors. As the hospital district with lower DP risk, HUS was characterized by the highest level of regional socioeconomic prosperity as well as high service richness and diversity. With a nationally average DP risk, Southwest Finland had the highest number of MHS personnel in full-time equivalents (FTE) per 100 000 inhabitants. Pirkanmaa, with a higher DP risk, had overall the lowest service richness and the lowest FTE of the three districts in all MHS, outpatient care and local services with gatekeeping. CONCLUSIONS: Our findings indicate that greater richness and diversity of MHS, especially in outpatient and community-based settings, may serve as indicators of a balanced, high-quality service system that is more effective in preventing mood disorder DP and meeting the different needs of the population. In addition, the need for sufficient resourcing in all MHS and outpatient services is indicated. We suggest using diversity indices to complement the measuring and reporting of regional service variation.

Socioeconomic status, psychotherapy duration, and return to work from disability due to common mental disorders.

OBJECTIVE: Low socioeconomic status (SES) is a risk factor for work disability due to common mental disorders (CMDs), one possible reason being inequal use of services. Psychotherapy is an evidence-based treatment for CMDs. This study examines socioeconomic and sociodemographic differences in psychotherapy attendance and an association of psychotherapy duration with return to work (RTW). METHODS: The study subjects (N = 12,263) were all Finnish citizens granted a disability pension (DP) due to CMDs in 2010-2012. Numbers of psychotherapy sessions (maximum 200) were collected from the nine-year interval around the DP grant. Socioeconomic and sociodemographic differences in psychotherapy duration (dependent variable) among DP recipients were studied using multinomial logistic regression models, likewise, the association between psychotherapy duration and RTW (dependent variable) among temporary DP recipients was examined. RESULTS: Higher SES, female gender, and younger age were positively associated with attending longer psychotherapies and surpassing the early treatment termination level (>10 sessions). Attending 11-60 psychotherapy sessions was positively associated with full RTW and partial RTW, whereas longer psychotherapies were not. Early termination was positively associated with partial RTW only. CONCLUSION: This study demonstrates varying tendencies among CMD patients from different backgrounds to attend long rehabilitative psychotherapies, which may create inequalities in RTW.

Impact of the first response unit on prehospital on-scene time among paramedic-suspected stroke patients: a retrospective before-after cohort study in Finland.

BACKGROUND: Revascularization of an occluded artery by either thrombolysis or mechanical thrombectomy is a time-critical intervention in ischaemic stroke. Each link in the stroke chain of survival should minimize the delay to definitive treatment in every possible way. In this study, we investigated the effect of routine dispatch of a first response unit (FRU) on prehospital on-scene time (OST) on stroke missions. METHODS: Medical dispatch of FRU together with an emergency medical service (EMS) ambulance was a routine strategy in the Tampere University Hospital area before 3 October 2018, after which the FRU has only been dispatched to medical emergencies on the decision of an EMS field commander. This study presents a retrospective before-after analysis of 2,228 paramedic-suspected strokes transported by EMSs to Tampere University Hospital. We collected data from EMS medical records from April 2016 to March 2021, and used statistical tests and binary logistic regression to detect the associations between the variables and the shorter and longer half of OSTs. RESULTS: The median OST of stroke missions was 19 min, IQR [14-25] min. The OST decreased when the routine use of the FRU was discontinued (19 [14-26] min vs. 18 [13-24] min, p < 0.001). The median OST with the FRU being the first at the scene (n = 256, 11%) was shorter than in cases where the FRU arrived after the ambulance (16 [12-22] min vs. 19 [15-25] min, p < 0.001). The OST with a stroke dispatch code was shorter than with non-stroke dispatches (18 [13-23] min vs. 22 [15-30] min, p < 0.001). The OST for thrombectomy candidates was shorter than that for thrombolysis candidates (18 [13-23] min vs. 19 [14-25], p = 0.01). The shorter half of OSTs were associated with the FRU arriving first at the scene, stroke dispatch code, thrombectomy transportation and urban location. CONCLUSION: The routine dispatch of the FRU to stroke missions did not decrease the OST unless the FRU was first to arrive at the scene. In addition, a correct stroke identification in the dispatch centre and thrombectomy candidate status decreased the OST.

Health check attendance association with health and study-related factors: a register-based cohort study of Finnish university entrants.

BACKGROUND: General health checks are an established component of preventive health care in many countries. Declining participation rates have raised concerns in health care providers. Understanding the reasons for attendance and non-attendance is necessary to improve the preventive health care system. The aim of this study was to examine health- and study-related factors associated with university entrants' health check attendance. METHODS: Since 2009, an electronic health questionnaire (eHQ) has been conducted yearly to all Finnish university entrants by the Finnish Student Health Service (FSHS) to screen students for a general health check. The questionnaire comprises 26 questions about health, health habits and studying. The study population consisted of the 3346 entrants from the 2011-2012 academic year who were referred to a health check based on their eHQ responses. The eHQ data were linked with health check attendance information. Multivariable logistic regression was used to study the associations between the questionnaire responses and non-attendance of the health check. RESULTS: Male sex (OR 1.6, 95% CI % 1.4-1.9) and low engagement with studies (OR 1.5, 95% CI 1.2-2.0) were the variables most strongly associated with non-attendance. Having low state of mind was negatively associated with health check non-attendance thus enhanced the health-check attendance (OR 0.6, 95% CI 0.5-0.8). CONCLUSIONS: The results suggest that providing health checks in student health care may serve as a way of reaching students with health concerns. However, motivating males and smokers to attend general health checks continue to be a challenge also in a university student population. That low engagement with studies associates with health check non-attendance points to need to improve collaboration between universities and student health care.

Socioeconomic factors and use of psychotherapy in common mental disorders predisposing to disability pension.

BACKGROUND: Research in high-income countries has identified low socioeconomic status as a risk factor for disability pension (DP) due to common mental disorders (CMDs). Psychotherapy is an evidence-based treatment for the majority of CMDs along with medication and it is often targeted to prevent work disability. This study examines socioeconomic differences in the use of rehabilitative psychotherapy in Finland, where citizens have universal health coverage, but psychotherapy is partly dependent on personal finance. METHODS: The study subjects (N = 22,501) were all the Finnish citizens granted a DP due to CMD between 2010 and 2015 and a comparison group (N = 57,732) matched based on age, gender, and hospital district. Socioeconomic differences in psychotherapy use were studied using logistic regression models. Socioeconomic status was defined by education, income, and occupation. Age, gender, and family status were also examined. RESULTS: A lower level of education, lower occupational status (blue-collar worker), male gender, and older age, were associated with less frequent psychotherapy use, in both groups. Education was the strongest component of socioeconomic status associated with psychotherapy use, but the role of income was not straightforward. Unemployment when approaching DP, but not otherwise, was a risk factor for not receiving rehabilitative psychotherapy. Socioeconomic disparities were not any smaller among CMD patients approaching DP than in the comparison group. CONCLUSION: This study demonstrates the disparity in the provision of psychotherapy for CMD patients, even on the verge of DP with an acute need for services. This disparity is partly related to a complex interplay of socioeconomic factors and the service system characteristics. Factors predisposing to unequal access to mental health services are presumably diverse and should be studied further.

Association between university students' two-staged health screening and student health care utilisation: register based observational study.

OBJECTIVES: The aim of this study was to explore how university students' participation in a two-staged health screening at the beginning of university studies associates with student health care utilisation in a 6-year follow-up. DESIGN: Nationwide, observational, register-based cohort study with a 6-year follow-up. SETTING: Student health care in Finland. Finnish Student Health Service (FSHS) provides statutory student health services to university students in Finland. The two-staged health screening of FSHS includes the electronic health questionnaire (eHQ) provided annually to university entrants and a subsequent health check, when necessary, based on students eHQ response. PARTICIPANTS: A national cohort of university entrants from the 2011-2012 academic year (N=15 723) was assessed. After exclusions the study population consisted of 12 972 students, n (female)=7368, n (male)=5604. OUTCOME MEASURES: The primary outcome measures were students' health service utilisation pattern obtained by clustering analyses method and the students' participation in different stages of the health examination process. RESULTS: Four distinguishable health care utilisation patterns were identified: (1) constant low use, (2) constant high use, (3) increasing use and (4) decreasing use. The students' OR for belonging to the constant high use group was significantly higher among females (OR 4.0, 95% CI 3.5 to 4.6) and students who attended the health check (OR 4.7, 95% CI 3.9 to 5.6). CONCLUSIONS: Participating in the two-staged health screening was associated with increase in health care utilisation. The process detects students with health problems.

Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study.

Aims: Altered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity. Methods: Serum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers. Results: Correlations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations. Conclusions: In cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored. Trial registry number: NCT00179777.

Contextual and mental health service factors in mental disorder-based disability pensioning in Finland - a regional comparison.

BACKGROUND: We investigated the regional differences in all mental disorder disability pensions (DP) between 2010 and 2015 in Finland, and separately in mood disorders and non-affective psychotic disorder DP. We also studied the contribution of several district-level contextual and mental health service factors to mental disorder DP. METHODS: Subjects were all those granted mental disorder DP for the first time between 2010 and 2015 in Finland (N = 36,879). Associations between the district-level contextual and mental health service factors and regional DP risks collected from the year 2015 were studied with negative binomial regression analysis in the Finnish hospital districts. The population number on the age (18 to 65 years), gender, occupational status and residential hospital district of the Finnish population from 2015 was used as exposure in the model. RESULTS: Significant differences in the regional mental disorder DP risks between and within hospital districts did not appear to follow the traditional Finnish health differences. A lower risk of DP was associated with contextual indicators of higher regional socioeconomic level. Furthermore, population density as a proxy for access to mental health services indicated a higher regional DP risk for lower density in all mental (IRR 1.10; 95% CI 1.06-1.14) and mood disorder (IRR 1.12; 95% CI 1.08-1.16) DP. Both the highest and the lowest regional numbers of all mental health outpatient visits were associated with a higher DP risk in all mental and mood disorder DP, whereas particularly low regional numbers of inpatient treatment periods and of patients were associated with a lower risk of DP. CONCLUSIONS: In this comprehensive population-level study, we found evidence of significant regional variation in mental disorder DP and related district-level factors. This variation may at least partly relate to differences in regional mental health service systems and treatment practices. Adapting to the needs of the local population appears to be indicated for both regional mental health service systems and treatment practices to achieve optimal performance.

Serum fatty acids and risk of developing islet autoimmunity: A nested case-control study within the TRIGR birth cohort.

BACKGROUND: Circulating fatty acids have been linked to development of type 1 diabetes. OBJECTIVES: To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children. METHODS: A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. The present study included 244 case children positive for at least two islet autoantibodies (ICA, IAA, GADA, and IA-2A) and two control children were matched for country and age. Proportions of 26 serum fatty acids at cord blood and at 6, 12, and 18 months of age were assessed using gas-chromatography. RESULTS: The average proportions of the following fatty acids were associated with an increased risk of islet autoimmunity, adjusted for sex, HLA risk, and maternal type 1 diabetes: pentadecanoic acid (15:0) (OR 3.41: 95% CI 1.70, 6.85), heptadecanoic acid (iso 17:0) (2.64: 1.62, 4.28) and (anteiso 17:0) (2.27: 1.39, 3.70), stearic acid (18:0) (23.8: 2.32, 244.6), and conjugated linoleic acid (18:2n-7) (2.60: 1.47, 4.59). Breastfeeding and not having maternal type 1 diabetes were positively associated with levels of the above-mentioned fatty acids. N-3 fatty acids were not consistently associated with islet autoimmunity. CONCLUSIONS: We found direct associations of pentadecanoic acid, heptadecanoic acid, stearic acid, and conjugated linoleic acid with the risk of islet autoimmunity. Further studies are needed to understand the complex role of fatty acids in the development of type 1 diabetes.

Associations between e-health questionnaire responses, health checks and graduation: Finnish register-based study of 2011-2012 university entrants.

OBJECTIVE: To evaluate the association between health and study-related factors measured by an Electronic Health Questionnaire (eHQ), participation in a health examination process and graduation in a university student population. DESIGN: Nationwide, retrospective, register-based cohort study with a 6-year follow-up. SETTING: Student health care in Finland. Finnish Student Health Service (FSHS) provides statutory student health services to university students in Finland. The health examination process of FSHS includes the eHQ provided annually to university entrants and a subsequent health check when necessary based on students' eHQ response. PARTICIPANTS: A national cohort of university entrants from the 2011-2012 academic year (n=14 329, n (female)=8075, n (male)=6254). OUTCOME MEASURES: The primary outcome measure was graduation, measured based on whether a student had completed a bachelor's, licentiate or master's degree during the 6-year follow-up. RESULTS: Some 72% of the women and 60% of the men had graduated during the follow-up. The predictors in the eHQ associated with non-graduation differed by sex. Among the women's low enthusiasm about studies (OR 2.6, 95% CI 1.9 to 3.6), low engagement with studies (OR 2.5, 95% CI 1.8 to 3.4) and daily smoking (OR 1.9, 95% CI 1.4 to 2.6) were the strongest predictors to non-graduation. Among the men, low engagement with studies (OR 3.7, 95% CI 2.5 to 5.5) and obesity (body mass index≥35) (OR 4.0, 95% CI 1.9 to 8.8) were the strongest predictors to non-graduation. Not attending the health check when referred was associated with non-graduation in both sexes: the OR for not graduating was 1.6 (95% CI 1.3 to 1.9) in women and 1.3 (95% CI 1.0 to 1.6) in men. CONCLUSIONS: Engagement and enthusiasm about studying in the first year are important predictors of graduation and therefore a potential intervention target. Health promotion initiatives conducted early in the studies may have a positive effect on students' academic achievement.

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response.

Socioeconomic factors in disability retirement due to mental disorders in Finland.

BACKGROUND: Previous research has identified low socioeconomic status (SES) as an epidemiological risk factor for early retirement and disability pension (DP) due to mental disorders. This study aims to examine these associations in greater detail, with separate consideration of the risk factors for mood disorders (F30-39) and non-affective psychotic disorder (F20-29) DP. METHODS: In this case-control setting the subjects (N = 36 879) were all those granted DP due to a mental disorder for the first time between 2010 and 2015 in Finland. All the subjects were matched with three controls for their gender, age and hospital district (N = 94 388). Three measures of dimensions of SES were used: education, income and occupational status, as well as family type as a control factor. Differences between DP recipients and controls, and between diagnostic groups, were studied using calculated characteristics and conditional logistic regression models. RESULTS: DP recipients often lived alone and had low educational and income levels. These characteristics were more prominent in non-affective psychotic disorder than in mood disorder DP. In white-collar occupational groups, the risk of DP was greater compared with blue-collar workers. Students were associated with the highest level of risk for all mental and mood disorder DPs. CONCLUSIONS: We found evidence of SES factors associating with mental disorder-related severe loss of working and studying ability in a disorder-specific way. Notably, white-collar workers had an increased risk of mental disorder DP. This could be related to the psychosocially demanding contemporary working life in non-manual work.

Screening University Students for Health Checks With an Electronic Health Questionnaire in Finland: Protocol for a Retrospective, Register-Based Cohort Study.

BACKGROUND: Health questionnaires and health checks are an established part of preventive health care services in Finland. However, only very limited research of these has been conducted. The Finnish Student Health Service (FSHS) provides primary health care services to all bachelor's and master's degree university students (approximately 134,500 students) in Finland. FSHS's statutory health examination process of university entrants includes an electronic health questionnaire (eHQ) and, based on the students' eHQ responses, a subsequent health check if necessary. To our knowledge, no previous studies have been published on the use of questionnaires for screening students for general health checks. OBJECTIVE: The general aim of the study is to evaluate the health examination process of university entrants. The objectives are to determine how students' self-reported health in the eHQ and participation in the health examination process are associated with graduation, mental health problems, and the use of student health care services. METHODS: This is an ongoing, nationwide, retrospective, register-based cohort study with a 6-year follow-up. The study population is the cohort of university entrants (N=15,723) from the 2011-2012 academic year. These students were sent the eHQ, which consisted of 26 questions about health, health habits, social relations, and studying. Based on the eHQ responses, students were referred to one of the following interventions: (1) a health check, (2) an appointment other than a health check (eg, physiotherapy), or (3) electronic feedback to support a healthy lifestyle, when the other interventions were not necessary. Multiple comparisons will be made within these groups using logistic regression. The primary outcome variables are graduation, having a mental health problem, and attending a health check. The use of FSHS health care services will be studied with the cluster analysis method. The data have been obtained from three nationwide registers: the eHQ register, the medical records of FSHS, and the Higher education achievement register. The data have been linked using personal identity codes. RESULTS: As of August 2019, the data collection and processing are complete and the statistical analyses are in progress. Preliminary results are expected in autumn 2019. Further publications are expected in 2020, and two PhD theses are expected to be completed by the end of 2022. CONCLUSIONS: Studying practical procedures in primary health care is highly important for resource allocation and the development of evidence-based processes. This study will be the first to assess the usage of a health questionnaire in screening students for health checks. The findings of this study will contribute to the field of preventive health care. The main practical implication is the development of the FSHS's health examination process. We hypothesize that participation in the health examination process enhances academic achievement and the detection of university students' mental health problems early on in their studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14535.

In-vitro dissolution characteristics and human adipose stem cell response to novel borophosphate glasses.

The main drawbacks of traditional silicate bioactive glasses are their narrow hot forming domain and noncongruent dissolution. In this article, we report on new borophosphate glasses [xMn Om + (100 - x) (47.5P2 O5 + 2.5B2 O3 + 10Na2 O + 20CaO + 20SrO)], Mn Om being CuO, Ag2 O, and CeO2 , having high thermal processability, hence suitable for fiber drawing and sintering into scaffolds. Furthermore, the glasses dissolve congruently in simulated body fluid (SBF) and TRIS buffer solution, eventually leading to the precipitation of a reactive layer. Human adipose stem cells (hASC) were cultured in media enriched with glass extract at different dilutions, to investigate the optimal ion concentration for cell survival. Cells grew in all the extracts, except in the undiluted Cu-doped glass extract. At dilution 1:10, the lactate dehydrogenase (LDH) activity and cell proliferation were comparable to the control, while at 1:100, the cells proliferated faster than the control. Thus, the reference (undoped), Ag and Ce-doped glasses were found to be suitable for cell viability and proliferation. Cytotoxicity assessments using the LDH assay indeed revealed the high cytotoxicity of the Cu extract. This raises questions about the use of Cu in bioactive glasses and its optimal concentration as a dopant.

Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors.

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-κB, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be 'sensed' as pathogens by immune cells.

Vipie: web pipeline for parallel characterization of viral populations from multiple NGS samples.

BACKGROUND: Next generation sequencing (NGS) technology allows laboratories to investigate virome composition in clinical and environmental samples in a culture-independent way. There is a need for bioinformatic tools capable of parallel processing of virome sequencing data by exactly identical methods: this is especially important in studies of multifactorial diseases, or in parallel comparison of laboratory protocols. RESULTS: We have developed a web-based application allowing direct upload of sequences from multiple virome samples using custom parameters. The samples are then processed in parallel using an identical protocol, and can be easily reanalyzed. The pipeline performs de-novo assembly, taxonomic classification of viruses as well as sample analyses based on user-defined grouping categories. Tables of virus abundance are produced from cross-validation by remapping the sequencing reads to a union of all observed reference viruses. In addition, read sets and reports are created after processing unmapped reads against known human and bacterial ribosome references. Secured interactive results are dynamically plotted with population and diversity charts, clustered heatmaps and a sortable and searchable abundance table. CONCLUSIONS: The Vipie web application is a unique tool for multi-sample metagenomic analysis of viral data, producing searchable hits tables, interactive population maps, alpha diversity measures and clustered heatmaps that are grouped in applicable custom sample categories. Known references such as human genome and bacterial ribosomal genes are optionally removed from unmapped ('dark matter') reads. Secured results are accessible and shareable on modern browsers. Vipie is a freely available web-based tool whose code is open source.