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  • Räsänen, Joel; Huovinen, Joel; Korhonen, Ville E; Junkkari, Antti; Kastinen, Sami; Komulainen, Simo; Oinas, Minna; Avellan, Cecilia; Frantzen, Janek; Rinne, Jaakko; Ronkainen, Antti; Kauppinen, Mikko; Lönnrot, Kimmo; Perola, Markus; Koivisto, Anne M; Remes, Anne M; Soininen, Hilkka; Hiltunen, Mikko; Helisalmi, Seppo; Kurki, Mitja I; Jääskeläinen, Juha E; Leinonen, Ville (BioMed Central, 2020)
    Abstract Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
  • Välkki, Kirsi J; Thomson, Katariina H; Grönthal, Thomas S C; Junnila, Jouni J T; Rantala, Merja H J; Laitinen-Vapaavuori, Outi M; Mölsä, Sari H (BioMed Central, 2020)
    Abstract Background Surgical site infections (SSI) are associated with increased morbidity and mortality. To lower the incidence of SSI, antimicrobial prophylaxis is given 30–60 min before certain types of surgeries in both human and veterinary patients. However, due to the increasing concern of antimicrobial resistance, the benefit of antimicrobial prophylaxis in clean orthopaedic and neurosurgeries warrants investigation. The aims of this retrospective cross-sectional study were to review the rate of SSI and evaluate the compliance with antimicrobial guidelines in dogs at a veterinary teaching hospital in 2012–2016. In addition, possible risk factors for SSI were assessed. Results Nearly all dogs (377/406; 92.9%) received antimicrobial prophylaxis. Twenty-nine dogs (7.1%) did not receive any antimicrobials and only four (1.1%) received postoperative antimicrobials. The compliance with in-house and national protocols was excellent regarding the choice of prophylactic antimicrobial (cefazolin), but there was room for improvement in the timing of prophylaxis administration. Follow-up data was available for 89.4% (363/406) of the dogs. Mean follow-up time was 464 days (range: 3–2600 days). The overall SSI rate was 6.3%: in orthopaedic surgeries it was 6.7%, and in neurosurgeries it was 4.2%. The lowest SSI rates (0%) were seen in extracapsular repair of cranial cruciate ligament rupture, ulnar ostectomy, femoral head and neck excision, arthrotomy and coxofemoral luxation repair. The highest SSI rate (25.0%) was seen in arthrodesis. Omission of antimicrobials did not increase the risk for SSI (P = 0.56; OR 1.7; CI95% 0.4–5.0). Several risk factors for SSI were identified, including methicillin-resistant Staphylococcus pseudintermedius carriage (P = 0.02; OR 9.0; CI95% 1.4–57.9) and higher body temperature (P = 0.03; OR 1.69; CI95% 1.0–2.7; mean difference + 0.4 °C compared to dogs without SSI). Conclusions Antimicrobial prophylaxis without postoperative antimicrobials is sufficient to maintain the overall rate of SSI at a level similar to published data in canine clean orthopedic and neurosurgeries.
  • Majaluoma, Susa; Seppälä, Tellervo; Kautiainen, Hannu; Korhonen, Päivi (BioMed Central, 2020)
    Abstract Background Type D personality is a combination of high negative affectivity (NA) and high social inhibition (SI). This personality trait is suspected to impair cardiovascular patients’ recovery. The 2016 European Guidelines on cardiovascular disease prevention in clinical practice recommend screening of psychosocial risk factors as Type D personality. The aim of this study was to assess the relationship between Type D personality and Metabolic syndrome (MetS) in working-age female population. Methods Six hundred thirty-four female employees with mean age of 48 ± 10 years were evaluated. Type D personality and its components (NA) and (SI) were screened with DS14 questionnaire. The definition of MetS was based on measurements done by trained medical staff. We investigated the relationship between Mets and Type D personality, NA and SI using the logistic regression models adjusting for age, education years, leisure-time physical activity, smoking, alcohol use and depressive symptoms. Results The prevalence of Type D personality was 10.6% (n = 67) [95% CI: 8.3 to 13.2] and MetS 34.7% (n = 220). Type D personality or its subcomponents were not associated with MetS. Women with Type D personality had significantly worse quality of sleep and lower LTPA. They were also more often unsatisfied with their economic situation, they had more often depressive symptoms and psychiatric disorders than non-D type persons. There were no differences in risk factors for cardiovascular diseases. Conclusion Screening for Type D personality among working- age, reasonably healthy female population seems not to be practical method for finding persons with risk for cardiovascular disease.
  • Hublin, Christer; Haasio, Lassi; Kaprio, Jaakko (BioMed Central, 2020)
    Abstract Background Sleep deprivation is often claimed to be increasingly common, but most studies show small changes in sleep duration over the last decades. Our aim was to analyze long-term patterns in self-reported sleep duration in a population-based cohort. Methods Members of the Older Finnish Twin Cohort have responded to questionnaires in 1975 (N = 30,915 individuals, response rate 89%, mean age 36 years), 1981 (24,535, 84%, 41 years), 1990 (12,450, 77%, 44 years), and 2011 (8334, 72%, 60 years). Weibull regression models were used to model the effects of follow-up time and age simultaneously. Results Sleep duration has decreased in all adult age groups and in both genders. The mean duration was in men 7.57 h in 1975 and 7.39 in 2011, and in women 7.69 and 7.37, respectively. The decrease was about 0.5 min in men and 0.9 in women per year of follow-up. In the age-group 18–34 years, mean sleep length was 7.69 h in 1975 and 7.53 in 1990. Among 35–54-year-old it was 7.57 h in 1975 and 7.34 in 2011, and in the age group of 55+ year olds 7.52 and 7.38, correspondingly. The change was largest in middle-aged group: about 23 min or about 0.6 min per year of follow-up. Conclusions There has been a slight decrease in mean sleep duration during the 36-year follow-up. Although the sleep duration was longer in 1970s and 1980s, the probable main cause for the change in this study population is the effect of aging.
  • Hälli, Outi; Haimi-Hakala, Minna; Oliviero, Claudio; Heinonen, Mari (BioMed Central, 2020)
    Abstract Background Chronic pleurisy is a common finding in slaughtered pigs in post-mortem meat inspection. The prevalence of pleurisy has been increasing during the last decade also in Finland. The aim of this prospective case-control study was to search for environmental, infectious and management-related herd-level risk factors for pleurisy in the slaughterhouse. Altogether 46 Finnish pig herds, including 25 control (low pleurisy prevalence in meat inspection) and 21 case (high pleurisy) herds, were enrolled in the study and visited during the tenth week of the rearing period of finishing pigs. Herd personnel were asked about basic herd information, management and environmental factors. Selected pigs were examined clinically, environmental parameters were measured and 15 blood samples per herd were taken during herd visits. Antibodies against Actinobacillus pleuropneumonia serotype 2 (APP2) and ApxIV toxin and swine influenza virus were measured. After the slaughter of study pigs, meat inspection results of the batch were gathered from slaughterhouses. Multivariate logistic regression model was built to identify possible risk factors for a herd to be a case herd (i.e. having high pleurisy values). Results Finishing herd type and herd size were observed to act as risk factors. None of clinical signs of pigs, management-related factors or environmental measurements were associated with herd status. Conclusions As previously known, in endemic and subclinical infections such as APP, herd factors are important, but detailed risk factors seem to be difficult to identify.
  • Almangush, Alhadi; Mäkitie, Antti A; Hagström, Jaana; Haglund, Caj; Kowalski, Luiz P; Nieminen, Pentti; Coletta, Ricardo D; Salo, Tuula; Leivo, Ilmo (BioMed Central, 2020)
    Abstract Background Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC). Methods A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining. Results We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52–5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12–4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001). Conclusions Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice.
  • Hakola, Riina; Leino, Timo; Luukkonen, Ritva; Kauppi, Paula (BioMed Central, 2020)
    Abstract Background The focus in occupational health check-ups is in work and health, but they offer also a possibility to assess health behavior and give guidance e.g. on weight control. We wanted to study whether having occupational health checks-up, receiving physicians’ advice to change health behavior or participation in health promotion programs had an effect on obesity in a five-year follow-up from 1998 to 2003 in asthmatic and non-asthmatic workers. Methods Altogether 23,220 individuals aged 20–54 years were picked up from a randomized Finnish population sample. Univariate and multivariate logistic regression analysis was used to calculate the risk for obesity in 2003. The variables used in the modelling were gender, age, smoking, asthma, depression, and physical workload. Results Both asthmatic and non-asthmatic workers gained weight during the follow-up. Of the asthmatics 48 and 47% of the non-asthmatics had occupational health-check-up in the last 5 years. Of the asthmatics 18 and 14% of the non-asthmatics had received physician’s advice to change their health behavior (p < 0.001). Associated factors for obesity (BMI > 30) in 2003 were gender (men OR 1.19), older age (OR 1.25), smoking (OR 1.07) or depression (OR 1.44). Conclusions Results show that having occupational health checks-up or receiving physicians’ advice to change health behavior or participation in health promotion programs did not stop gain of weight during a five-year follow-up. Asthmatic workers did not differ from non-asthmatics. Male gender, older age, smoking, and depression were associated with obesity but not the physical workload.
  • Lado, Sara; Elbers, Jean P; Rogers, Mark F; Melo-Ferreira, José; Yadamsuren, Adiya; Corander, Jukka; Horin, Petr; Burger, Pamela A (BioMed Central, 2020)
    Abstract Background Immune-response (IR) genes have an important role in the defense against highly variable pathogens, and therefore, diversity in these genomic regions is essential for species’ survival and adaptation. Although current genome assemblies from Old World camelids are very useful for investigating genome-wide diversity, demography and population structure, they have inconsistencies and gaps that limit analyses at local genomic scales. Improved and more accurate genome assemblies and annotations are needed to study complex genomic regions like adaptive and innate IR genes. Results In this work, we improved the genome assemblies of the three Old World camel species – domestic dromedary and Bactrian camel, and the two-humped wild camel – via different computational methods. The newly annotated dromedary genome assembly CamDro3 served as reference to scaffold the NCBI RefSeq genomes of domestic Bactrian and wild camels. These upgraded assemblies were then used to assess nucleotide diversity of IR genes within and between species, and to compare the diversity found in immune genes and the rest of the genes in the genome. We detected differences in the nucleotide diversity among the three Old World camelid species and between IR gene groups, i.e., innate versus adaptive. Among the three species, domestic Bactrian camels showed the highest mean nucleotide diversity. Among the functionally different IR gene groups, the highest mean nucleotide diversity was observed in the major histocompatibility complex. Conclusions The new camel genome assemblies were greatly improved in terms of contiguity and increased size with fewer scaffolds, which is of general value for the scientific community. This allowed us to perform in-depth studies on genetic diversity in immunity-related regions of the genome. Our results suggest that differences of diversity across classes of genes appear compatible with a combined role of population history and differential exposures to pathogens, and consequent different selective pressures.
  • Konerding, Uwe; Bowen, Tom; Elkhuizen, Sylvia G; Faubel, Raquel; Forte, Paul; Karampli, Eleftheria; Malmström, Tomi; Pavi, Elpida; Torkki, Paulus (BioMed Central, 2020)
    Abstract Background Visits to the primary diabetes care provider play a central role in diabetes care. Therefore, patients should attend their primary diabetes care providers whenever a visit is necessary. Parameters that might affect whether this condition is fulfilled include accessibility (in terms of travel distance and travel time to the practice), as well as aspects of service quality (for example in-practice waiting time and quality of the provider’s communication with the patient). The relationships of these variables with the frequency of visits to the primary diabetes care provider are investigated. Methods The investigation is performed with questionnaire data of 1086 type 2 diabetes patients from study regions in England (213), Finland (135), Germany (218), Greece (153), the Netherlands (296) and Spain (71). Data were collected between October 2011 and March 2012. Data were analysed using log-linear Poisson regression models with self-reported numbers of visits in a year to the primary diabetes care provider as the criterion variable. Predictor variables of the core model were: country; gender; age; education; stage of diabetes; heart problems; previous stroke; problems with lower extremities; problems with sight; kidney problems; travel distance and travel time; in-practice waiting time; and quality of communication. To test region-specific characteristics, the interaction between the latter four predictor variables and study region was also investigated. Results When study regions are merged, travel distance and in-practice waiting time have a negative effect, travel time no effect and quality of communication a positive effect on visit frequency (with the latter effect being by far largest). When region specific effects are considered, there are strong interaction effects shown for travel distance, in-practice waiting time and quality of communication. For travel distance, as well as for in-practice waiting time, there are region-specific effects in opposite directions. For quality of communication, there are only differences in the strength with which visit frequency increases with this variable. Conclusions The impact of quality of communication on visit frequency is the largest and is stable across all study regions. Hence, increasing quality of communication seems to be the best approach for increasing visit frequency.
  • Vuorinen, Pekka J; Rokka, Mervi; Ritvanen, Tiina; Käkelä, Reijo; Nikonen, Soili; Pakarinen, Tapani; Keinänen, Marja (BioMed Central, 2020)
    Abstract Salmonines in the Baltic Sea and North American lakes suffer from thiamine (vitamin B1) deficiency, which is connected to an abundant lipid-rich diet containing substantial amounts of polyunsaturated fatty acids (PUFAs). In the Baltic region, this is known as the M74 syndrome. It affects both adult salmon (Salmo salar) and especially their offspring, impairing recruitment. However, very little is known about the thiamine and lipid metabolism of salmon during feeding and spawning migrations in the Baltic Sea. In this study, salmon females were sampled along the spawning run from the southern Baltic Proper in four locations at sea and finally at spawning in a river at the Bothnian Bay in a year with insignificant M74 mortality. Changes in concentrations of thiamine and its components in muscle, ovaries, and the liver and other biochemical indices potentially relating to lipid and fatty acid metabolism were investigated. The results provide further evidence of the role of peroxidation of PUFAs in eliciting thiamine deficiency in salmon: During the entire spawning run, the muscle total lipid content decreased by 50%, palmitic acid (16:0) by 62%, and docosahexaenoic acid (DHA, 22:6n-3) by 45%. The concentration of total thiamine decreased significantly until the spawning in the liver and ovaries, 66 and 70% respectively. In the muscle, the proportion of thiamine pyrophosphate of total thiamine increased with the use of muscular lipid stores. There was no trend in the concentration of total carotenoids during the spawning run. The doubling of the concentration of hepatic malondialdehyde indicated peroxidation of PUFAs, and the mobilisation of body lipids suppressed the activity of glucose-6-phosphate dehydrogenase, as consumed dietary lipids would also have done.
  • Raju, Sajan C; Viljakainen, Heli; Figueiredo, Rejane A O; Neuvonen, Pertti J; Eriksson, Johan G; Weiderpass, Elisabete; Rounge, Trine B (BioMed Central, 2020)
    Abstract Background The human microbiota contributes to health and well-being. Antimicrobials (AM) have an immediate effect on microbial diversity and composition in the gut, but next to nothing is known about their long-term contribution to saliva microbiota. Our objectives were to investigate the long-term impact of AM use on saliva microbiota diversity and composition in preadolescents. We compared the lifetime effects by gender and AMs. We used data from 808 randomly selected children in the Finnish Health In Teens (Fin-HIT) cohort with register-based data on AM purchases from the Social Insurance Institution of Finland. Saliva microbiota was assessed with 16S rRNA (V3-V4) sequencing. The sequences were aligned to the SILVA ribosomal RNA database and classified and counted using the mothur pipeline. Associations between AM use and alpha-diversity (Shannon index) were identified with linear regression, while associations between beta-diversity (Bray-Curtis dissimilarity) and low, medium or high AM use were identified with PERMANOVA. Results Of the children, 53.6% were girls and their mean age was 11.7 (0.4) years. On average, the children had 7.4 (ranging from 0 to 41) AM prescriptions during their lifespan. The four most commonly used AMs were amoxicillin (n = 2622, 43.7%), azithromycin (n = 1495, 24.9%), amoxicillin-clavulanate (n = 1123, 18.7%) and phenoxymethylpenicillin (n = 408, 6.8%). A linear inverse association was observed between the use of azithromycin and Shannon index (b − 0.015, p value = 0.002) in all children, the effect was driven by girls (b − 0.032, p value = 0.001), while not present in boys. Dissimilarities were marked between high, medium and low users of all AMs combined, in azithromycin users specifically, and in boys with amoxicillin use. Amoxicillin and amoxicillin-clavulanate use was associated with the largest decrease in abundance of Rikenellaceae. AM use in general and phenoxymethylpenicillin specifically were associated with a decrease of Paludibacter and pathways related to amino acid degradations differed in proportion between high and low AM users. Conclusions A systematic approach utilising reliable registry data on lifetime use of AMs demonstrated long-term effects on saliva microbiota diversity and composition. These effects are gender- and AM-dependent. We found that frequent lifelong use of AMs shifts bacterial profiles years later, which might have unforeseen health impacts in the future. Our findings emphasise a concern for high azithromycin use, which substantially decreases bacterial diversity and affects composition as well. Further studies are needed to determine the clinical implications of our findings. Video Abstract
  • Lloyd-Williams, Ffion; Hyseni, Lirije; Guzman-Castillo, Maria; Kypridemos, Chris; Collins, Brendan; Capewell, Simon; Schwaller, Ellen; O’Flaherty, Martin (BioMed Central, 2020)
    Abstract Background Stakeholder engagement is being increasingly recognised as an important way to achieving impact in public health. The WorkHORSE (Working Health Outcomes Research Simulation Environment) project was designed to continuously engage with stakeholders to inform the development of an open access modelling tool to enable commissioners to quantify the potential cost-effectiveness and equity of the NHS Health Check Programme. An objective of the project was to evaluate the involvement of stakeholders in co-producing the WorkHORSE computer modelling tool and examine how they perceived their involvement in the model building process and ultimately contributed to the strengthening and relevance of the modelling tool. Methods We identified stakeholders using our extensive networks and snowballing techniques. Iterative development of the decision support modelling tool was informed through engaging with stakeholders during four workshops. We used detailed scripts facilitating open discussion and opportunities for stakeholders to provide additional feedback subsequently. At the end of each workshop, stakeholders and the research team completed questionnaires to explore their views and experiences throughout the process. Results 30 stakeholders participated, of which 15 attended two or more workshops. They spanned local (NHS commissioners, GPs, local authorities and academics), third sector and national organisations including Public Health England. Stakeholders felt valued, and commended the involvement of practitioners in the iterative process. Major reasons for attending included: being able to influence development, and having insight and understanding of what the tool could include, and how it would work in practice. Researchers saw the process as an opportunity for developing a common language and trust in the end product, and ensuring the support tool was transparent. The workshops acted as a reality check ensuring model scenarios and outputs were relevant and fit for purpose. Conclusions Computational modellers rarely consult with end users when developing tools to inform decision-making. The added value of co-production (continuing collaboration and iteration with stakeholders) enabled modellers to produce a “real-world” operational tool. Likewise, stakeholders had increased confidence in the decision support tool’s development and applicability in practice.
  • Santio, Niina M; Vainio, Veera; Hoikkala, Tuuli; Mung, Kwan L; Lång, Mirka; Vahakoski, Riitta; Zdrojewska, Justyna; Coffey, Eleanor T; Kremneva, Elena; Rainio, Eeva-Marja; Koskinen, Päivi J (BioMed Central, 2020)
    Abstract Background The PIM family kinases promote cancer cell survival and motility as well as metastatic growth in various types of cancer. We have previously identified several PIM substrates, which support cancer cell migration and invasiveness. However, none of them are known to regulate cellular movements by directly interacting with the actin cytoskeleton. Here we have studied the phosphorylation-dependent effects of PIM1 on actin capping proteins, which bind as heterodimers to the fast-growing actin filament ends and stabilize them. Methods Based on a phosphoproteomics screen for novel PIM substrates, we have used kinase assays and fluorescence-based imaging techniques to validate actin capping proteins as PIM1 substrates and interaction partners. We have analysed the functional consequences of capping protein phosphorylation on cell migration and adhesion by using wound healing and real-time impedance-based assays. We have also investigated phosphorylation-dependent effects on actin polymerization by analysing the protective role of capping protein phosphomutants in actin disassembly assays. Results We have identified capping proteins CAPZA1 and CAPZB2 as PIM1 substrates, and shown that phosphorylation of either of them leads to increased adhesion and migration of human prostate cancer cells. Phosphorylation also reduces the ability of the capping proteins to protect polymerized actin from disassembly. Conclusions Our data suggest that PIM kinases are able to induce changes in actin dynamics to support cell adhesion and movement. Thus, we have identified a novel mechanism through which PIM kinases enhance motility and metastatic behaviour of cancer cells. Video abstract Graphical abstract
  • Hemminki, Kari; Srivastava, Aayushi; Rachakonda, Sivaramakrishna; Bandapalli, Obul; Nagore, Eduardo; Hemminki, Akseli; Kumar, Rajiv (BioMed Central, 2020)
    Abstract Background When germline mutations are suspected as causal in cancer, patient DNA may be sequenced to detect variants in relevant genes. If a particular mutation has not been reported in reliable family studies, genetic counselors are facing a dilemma of appropriately informing patients. Many sequencing facilities provide an interpretation of the findings based on the available sequence databases or on prediction tools that are curated from bioinformatics and mechanistic datasets. The counseling dilemma is exacerbated if the pedigree data are not informative but the in silico predictions suggest pathogenicity. Methods We present here a real world example of the c.256G > A CDKN2A variant, which was detected in one melanoma patient where two siblings were diagnosed with melanoma in situ. We investigated a detailed family history of the affected siblings in order to survey probability of the cancer risks within the context to this mutation. Results This c.256G > A CDKN2A variant was detected in one of the brothers and in the melanoma-free mother while the other brother in the family tested negative. The variant had been previously described in one patient from a melanoma family. In the family under investigation, the mother’s 16 first-and second-degree relatives had survived past the median onset age for melanoma and none presented melanoma. We tested the variant using multiple bioinformatic tools that all predicted deleteriousness of the variant. The genetic counseling report to the melanoma patient stated that the CDKN2A variant was ‘likely pathogenic’ and the disease was defined as ‘likely hereditary melanoma’. Conclusions The pedigree data showed at the most a low penetrance variant, which, if taken into consideration, might have altered the provided diagnosis. When dealing with ‘practically’ unknown variants the counselors would be advised to incorporate a detailed family history rather than basing predictions on functionality provided by sequencing facilities.
  • Dudel, Christian; Myrskylä, Mikko (BioMed Central, 2020)
    Abstract Background Markov models are a key tool for calculating expected time spent in a state, such as active life expectancy and disabled life expectancy. In reality, individuals often enter and exit states recurrently, but standard analytical approaches are not able to describe this dynamic. We develop an analytical matrix approach to calculating the expected number and length of episodes spent in a state. Methods The approach we propose is based on Markov chains with rewards. It allows us to identify the number of entries into a state and to calculate the average length of episodes as total time in a state divided by the number of entries. For sampling variance estimation, we employ the block bootstrap. Two case studies that are based on published literature illustrate how our methods can provide new insights into disability dynamics. Results The first application uses a classic textbook example on prednisone treatment and liver functioning among liver cirrhosis patients. We replicate well-known results of no association between treatment and survival or recovery. Our analysis of the episodes of normal liver functioning delivers the new insight that the treatment reduced the likelihood of relapse and extended episodes of normal liver functioning. The second application assesses frailty and disability among elderly people. We replicate the prior finding that frail individuals have longer life expectancy in disability. As a novel finding, we document that frail individuals experience three times as many episodes of disability that were on average twice as long as the episodes of nonfrail individuals. Conclusions We provide a simple analytical approach for calculating the number and length of episodes in Markov chain models. The results allow a description of the transition dynamics that goes beyond the results that can be obtained using standard tools for Markov chains. Empirical applications using published data illustrate how the new method is helpful in unraveling the dynamics of the modeled process.
  • Rissanen, Annu-Riikka S; Jernman, Riina M; Gissler, Mika; Nupponen, Irmeli; Nuutila, Mika E (BioMed Central, 2020)
    An amendment to this paper has been published and can be accessed via the original article.
  • Rissanen, Annu-Riikka S; Jernman, Riina M; Gissler, Mika; Nupponen, Irmeli K; Nuutila, Mika E (BioMed Central, 2020)
    An amendment to this paper has been published and can be accessed via the original article.
  • Rajamäki, Minna-Liisa; Sikorskaite-Gudziuniene, Sidona; Sarmah, Nandita; Varjosalo, Markku; Valkonen, Jari P T (BioMed Central, 2020)
    Abstract Background Infection of plants by viruses interferes with expression and subcellular localization of plant proteins. Potyviruses comprise the largest and most economically damaging group of plant-infecting RNA viruses. In virus-infected cells, at least two potyviral proteins localize to nucleus but reasons remain partly unknown. Results In this study, we examined changes in the nuclear proteome of leaf cells from a diploid potato line (Solanum tuberosum L.) after infection with potato virus A (PVA; genus Potyvirus; Potyviridae) and compared the data with that acquired for healthy leaves. Gel-free liquid chromatography–coupled to tandem mass spectrometry was used to identify 807 nuclear proteins in the potato line v2–108; of these proteins, 370 were detected in at least two samples of healthy leaves. A total of 313 proteins were common in at least two samples of healthy and PVA-infected leaves; of these proteins, 8 showed differential accumulation. Sixteen proteins were detected exclusively in the samples from PVA-infected leaves, whereas other 16 proteins were unique to healthy leaves. The protein Dnajc14 was only detected in healthy leaves, whereas different ribosomal proteins, ribosome-biogenesis proteins, and RNA splicing–related proteins were over-represented in the nuclei of PVA-infected leaves. Two virus-encoded proteins were identified in the samples of PVA-infected leaves. Conclusions Our results show that PVA infection alters especially ribosomes and splicing-related proteins in the nucleus of potato leaves. The data increase our understanding of potyvirus infection and the role of nucleus in infection. To our knowledge, this is the first study of the nuclear proteome of potato leaves and one of the few studies of changes occurring in nuclear proteomes in response to plant virus infection.
  • Pulkkinen, Maria; Jousela, Irma; Engblom, Janne; Salanterä, Sanna; Junttila, Kristiina (BioMed Central, 2020)
    Abstract Background The shortened length of hospital stays (LOS) requires efficient and patient-participatory perioperative nursing approaches to enable early and safe discharge from hospitals for patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). The primary aim of this study was to explore the effect comparative to standard perioperative care of a new perioperative practice model (NPPM) on the LOS and the time points of the surgical care process in patients undergoing THA and TKA under spinal anesthesia. The secondary aim was to find out if any subgroups with different response could be found. Methods Patients scheduled for elective, primary THA and TKA were assessed for eligibility. A two-group parallel randomized clinical trial was conducted with an intervention group (n = 230) and control group (n = 220), totaling 450 patients. The patients in the intervention group were each designated with one named anesthesia nurse, who took care of the patient during the entire perioperative process and visited the patient postoperatively. The patients in the control group received standard perioperative care from different nurses during their perioperative processes and without postoperative visits. The surgical care process time points for each study patient were gathered from the operating room management software and hospital information system until hospital discharge. Results We did not find any statistically significant differences between the intervention and control groups regarding to LOS. Only slight differences in the time points of the surgical care process could be detected. The subgroup examination revealed that higher age, type of arthroplasty and ASA score 3–4 all separately caused prolonged LOS. Conclusion We did not find the new perioperative practice model to shorten either length of hospital stays or the surgical care process in patients undergoing THA and TKA. Further studies at the subgroup level (gender, old age, and ASA score 3 and 4) are needed to recognize the patients who might benefit most from the NPPM. Trial registration This study was registered in NIH under registration number NCT02906033 , retrospectively registered September 19, 2016.
  • Lommi, Henri; Koponen, Ismo T (Springer International Publishing, 2020)
    An amendment to this paper has been published and can be accessed via the original article.

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