Articles from BioMed Central


Recent Submissions

  • Tonetto, Leonardo; Lagerspetz, Eemil; Yi Ding, Aaron; Ott, Jörg; Tarkoma, Sasu; Nurmi, Petteri (Springer Berlin Heidelberg, 2021)
    Abstract Mobility is a fundamental characteristic of human society that shapes various aspects of our everyday interactions. This pervasiveness of mobility makes it paramount to understand factors that govern human movement and how it varies across individuals. Currently, factors governing variations in personal mobility are understudied with existing research focusing on explaining the aggregate behaviour of individuals. Indeed, empirical studies have shown that the aggregate behaviour of individuals follows a truncated Lévy-flight model, but little understanding exists of the laws that govern intra-individual variations in mobility resulting from transportation choices, social interactions, and exogenous factors such as location-based mobile applications. Understanding these variations is essential for improving our collective understanding of human mobility, and the factors governing it. In this article, we study the mobility laws of location-based gaming—an emerging and increasingly popular exogenous factor influencing personal mobility. We analyse the mobility changes considering the popular PokémonGO application as a representative example of location-based games and study two datasets with different reporting granularity, one captured through location-based social media, and the other through smartphone application logging. Our analysis shows that location-based games, such as PokémonGO, increase mobility—in line with previous findings—but the characteristics governing mobility remain consistent with a truncated Lévy-flight model and that the increase can be explained by a larger number of short-hops, i.e., individuals explore their local neighborhoods more thoroughly instead of actively visiting new areas. Our results thus suggest that intra-individual variations resulting from location-based gaming can be captured by re-parameterization of existing mobility models.
  • Bolomsky, Arnold; Vogler, Meike; Köse, Murat C; Heckman, Caroline A; Ehx, Grégory; Ludwig, Heinz; Caers, Jo (BioMed Central, 2021)
    An amendment to this paper has been published and can be accessed via the original article.
  • Reponen, Elina; Rundall, Thomas G; Shortell, Stephen M; Blodgett, Janet C; Juarez, Angelica; Jokela, Ritva; Mäkijärvi, Markku; Torkki, Paulus (BioMed Central, 2021)
    Abstract Background Reliable benchmarking in Lean healthcare requires widely relevant and applicable domains for outcome metrics and careful attention to contextual levels. These levels have been poorly defined and no framework to facilitate performance benchmarking exists. Methods We systematically searched the Pubmed, Scopus, and Web of Science databases to identify original articles reporting benchmarking on different contextual levels in Lean healthcare and critically appraised the articles. Scarcity and heterogeneity of articles prevented quantitative meta-analyses. We developed a new, widely applicable conceptual framework for benchmarking drawing on the principles of ten commonly used healthcare quality frameworks and four value statements, and suggest an agenda for future research on benchmarking in Lean healthcare. Results We identified 22 articles on benchmarking in Lean healthcare on 4 contextual levels: intra-organizational (6 articles), regional (4), national (10), and international (2). We further categorized the articles by the domains in the proposed conceptual framework: patients (6), employed and affiliated staff (2), costs (2), and service provision (16). After critical appraisal, only one fifth of the articles were categorized as high quality. Conclusions When making evidence-informed decisions based on current scarce literature on benchmarking in healthcare, leaders and managers should carefully consider the influence of context. The proposed conceptual framework may facilitate performance benchmarking and spreading best practices in Lean healthcare. Future research on benchmarking in Lean healthcare should include international benchmarking, defining essential factors influencing Lean initiatives on different levels of context; patient-centered benchmarking; and system-level benchmarking with a balanced set of outcomes and quality measures.
  • Kemp, Kirsi; Mertanen, Reija; Niemi-Murola, Leila; Lehtonen, Lasse; Castrén, Maaret (BioMed Central, 2021)
  • Laine, Merja K; Kautiainen, Hannu; Gissler, Mika; Pennanen, Pirjo; Eriksson, Johan G (BioMed Central, 2021)
    Abstract Background The impact of gestational diabetes mellitus (GDM) on the duration of breastfeeding varies between shortening and no impact. Breastfeeding seems to reduce both maternal and offspring risk for type 2 diabetes and offspring risk for overweight or obesity later in life. The aim of our study was to evaluate in primiparous women whether GDM had an influence on the duration of breastfeeding, and further, to evaluate the factors that influenced on the duration of breastfeeding. Methods The study cohort (N = 1089) consisted of all primiparous women with a Finnish background excluding women with pre-existing diabetes mellitus who lived in the city of Vantaa, Finland, gave birth to a singleton living child between 2009 and 2015, and with valid data on breastfeeding available. The diagnosis of GDM was based on a standard 75 g 2-h oral glucose tolerance test. Data were obtained from Finnish national registers and from the medical records of the city of Vantaa. Results No differences were observed in the duration of breastfeeding between women diagnosed with GDM and without GDM, 7.5 (Standard Deviation [SD] 3.7) months versus 7.9 (SD 3.5) months (p = 0.17). Women diagnosed with GDM breastfed boys for a longer duration than girls (maternal age, pre-pregnancy body mass index, marital status, educational attainment, duration of pregnancy, and smoking habits adjusted p = 0.042). Women who breastfed < 6 months were younger, were more likely smokers, had shorter education, and higher pre-pregnancy body mass index than women who breastfed over 6 months (p <  0.001 for linearity). Conclusions In primiparous women GDM did not influence breastfeeding duration. The positive health effects of breastfeeding should be emphasized especially in young, overweight and less educated women in order to minimize the risk of obesity and type 2 diabetes for themselves and their offspring.
  • Sarhadi, Virinder; Mathew, Binu; Kokkola, Arto; Karla, Tiina; Tikkanen, Milja; Rautelin, Hilpi; Lahti, Leo; Puolakkainen, Pauli; Knuutila, Sakari (BioMed Central, 2021)
    Abstract Background Gastric adenocarcinoma is associated with H. pylori infection and inflammation that can result in the dysbiosis of gastric microbiota. The association of intestinal microbiota with gastric adenocarcinoma subtypes or with gastric gastrointestinal stromal tumors (GIST) is however not well known. Therefore, we performed 16S rRNA gene sequencing on DNA isolated from stool samples of Finnish patients and controls to study differences in microbiota among different histological subtypes of gastric adenocarcinoma, gastric GIST and healthy controls. Results We found that gut microbiota alpha diversity was lowest in diffuse adenocarcinoma patients, followed by intestinal type and GIST patients, although the differences were not significant compared to controls. Beta-diversity analysis however showed significant differences in microbiota composition for all subtypes compared to controls. Significantly higher abundance of Enterobacteriaceae was observed in both adenocarcinoma subtypes, whereas lower abundance of Bifidobacteriaceae was seen only in diffuse adenocarcinoma and of Oscillibacter in intestinal adenocarcinoma. Both GIST and adenocarcinoma patients had higher abundance of Enterobacteriaceae and lower abundance of Lactobacillaceae and Oscillibacter while lower abundance of Lachnoclostridium, Bifidobacterium, Parabacteroides and Barnesiella was seen only in the adenocarcinoma patients. Conclusions Our analysis shows association of higher Enterobacteriaceae abundance with all types of gastric tumors. Therefore it could be potentially useful as a marker of gastric malignancies. Lower gut microbiota diversity might be indicative of poorly differentiated, invasive, advanced or aggressive tumors and could possibly be a prognostic marker for gastric tumors.
  • Zetterman, Teemu; Markkula, Ritva; Partanen, Juhani V; Miettinen, Teemu; Estlander, Ann-Mari; Kalso, Eija (BioMed Central, 2021)
    Abstract Background Fibromyalgia (FM) patients are likely to differ from healthy controls in muscle activity and in reactivity to experimental stress. Methods We compared psychophysiological reactivity to cognitive stress between 51 female FM patients aged 18 to 65 years and 31 age- and sex-matched healthy controls. They underwent a 20-minute protocol consisting of three phases of relaxation and two phases of cognitive stress. We recorded surface electromyography normalized to maximum voluntary muscle contraction (%EMG), the percentage of time with no muscle activity (EMG rest time), and subjective pain and stress intensities. We compared group reactivity using linear modelling and adjusted for psychological and life-style factors. Results The FM patients had a significantly higher mean %EMG (2.2 % vs. 1.0 %, p < 0.001), pain intensity (3.6 vs. 0.2, p < 0.001), and perceived stress (3.5 vs. 1.4, p < 0.001) and lower mean EMG rest time (26.7 % vs. 47.2 %, p < 0.001). In the FM patients, compared with controls, the pain intensity increased more during the second stress phase (0.71, p = 0.028), and the %EMG decreased more during the final relaxation phase (-0.29, p = 0.036). Within the FM patients, higher BMI predicted higher %EMG but lower stress. Leisure time physical activity predicted lower %EMG and stress and higher EMG rest time. Higher perceived stress predicted lower EMG rest time, and higher trait anxiety predicted higher pain and stress overall. Conclusions Our results suggest that repeated cognitive stress increases pain intensity in FM patients. FM patients also had higher resting muscle activity, but their muscle activity did not increase with pain. Management of stress and anxiety might help control FM flare-ups. Trial registration Retrospectively registered on ( NCT03300635 ).
  • Wang, Lijie; Mohammadnejad, Afsaneh; Li, Weilong; Lund, Jesper; Li, Shuxia; Clemmensen, Signe; Timofeeva, Maria; Soerensen, Mette; Mengel-From, Jonas; Christensen, Kaare; Hjelmborg, Jacob; Tan, Qihua (BioMed Central, 2021)
    Abstract Background Epigenetic inactivation of O6-methylguanine DNA-methyltransferase (MGMT) is associated with increased sensitivity to alkylating chemotherapeutic agents in glioblastoma patients. The genetic background underlying MGMT gene methylation may explain individual differences in treatment response and provide a clue to a personalized treatment strategy. Making use of the longitudinal twin design, we aimed, for the first time, to estimate the genetic contributions to MGMT methylation in a Danish twin cohort. Methods DNA-methylation from whole blood (18 monozygotic (MZ) and 25 dizygotic (DZ) twin pairs) repeated 10 years apart from the Longitudinal Study of Aging Danish Twins (LSADT) were used to search for genetic and environmental contributions to DNA-methylation at 170 CpG sites of across the MGMT gene. Both univariate and bivariate twin models were applied. The intraclass correlations, performed on cross-sectional data (246 MZ twin pairs) from an independent study population, the Middle-Aged Danish Twins (MADT), were used to assess the genetic influence at each CpG site of MGMT for replication. Results Univariate twin model revealed twelve CpG sites showing significantly high heritability at intake (wave 1, h2 > 0.43), and seven CpG sites with significant heritability estimates at end of follow-up (wave 2, h2 > 0.5). There were six significant CpG sites, located at the gene body region, that overlapped among the two waves (h2 > 0.5), of which five remained significant in the bivariate twin model, which was applied to both waves. Within MZ pair correlation in these six CpGs from MADT demarks top level of genetic influence. There were 11 CpGs constantly have substantial common environmental component over the 10 years. Conclusions We have identified 6 CpG sites linked to the MGMT gene with strong and persistent genetic control based on their DNA methylation levels. The genetic basis of MGMT gene methylation could help to explain individual differences in glioblastoma treatment response and most importantly, provide references for mapping the methylation Quantitative Trait Loci (meQTL) underlying the genetic regulation.
  • Sampieri, Gianluca; Namavarian, Amirpouyan; Levin, Marc; Philteos, Justine; Lee, Jong W; Koskinen, Anni; Lin, Vincent; Lee, John (BioMed Central, 2021)
    Abstract Objective Noise in operating rooms (OR) can have negative effects on both patients and surgical care workers. Noise can also impact surgical performance, team communication, and patient outcomes. Such implications of noise have been studied in orthopedics, neurosurgery, and urology. High noise levels have also been demonstrated in Otolaryngology-Head and Neck Surgery (OHNS) procedures. Despite this, no previous study has amalgamated the data on noise across all OHNS ORs to determine how much noise is present during OHNS surgeries. This study aims to review all the literature on noise associated with OHNS ORs and procedures. Methods Ovid Medline, EMBASE Classic, Pubmed, SCOPUS and Cochrane databases were searched following PRISMA guidelines. Data was collected on noise measurement location and surgery type. Descriptive results and statistical analysis were completed using Stata. Results This search identified 2914 articles. Final inclusion consisted of 22 studies. The majority of articles analyzed noise level exposures during mastoid surgery (18/22, 82%). The maximum noise level across all OHNS ORs and OHNS cadaver studies were 95.5 a-weighted decibels (dBA) and 106.6 c-weighted decibels (dBC), respectively (P = 0.2068). The mean noise level across all studies was significantly higher in OHNS cadaver labs (96.9 dBA) compared to OHNS ORs (70.1 dBA) (P = 0.0038). When analyzed together, the mean noise levels were 84.9 dBA. Conclusions This systematic review demonstrates that noise exposure in OHNS surgery exceeds safety thresholds. Further research is needed to understand how noise may affect team communication, surgical performance and patient outcomes in OHNS ORs. Graphical abstract
  • Aho, Velma T E; Houser, Madelyn C; Pereira, Pedro A B; Chang, Jianjun; Rudi, Knut; Paulin, Lars; Hertzberg, Vicki; Auvinen, Petri; Tansey, Malú G; Scheperjans, Filip (BioMed Central, 2021)
    Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
  • Cândido, Marcus V; Syrjä, Pernillä; Hanifeh, Mohsen; Lepajõe, Jaan; Salla, Kati; Kilpinen, Susanne; Noble, Peter-John M; Spillmann, Thomas (BioMed Central, 2021)
    Abstract Background Gastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations. Results The online survey included 232 responses. Logistic regression analysis recognized an association of vomiting with gagging, poor appetite and change in attitude. Recruitment for endoscopy included 16 BSD in Group A (mean age 9.1 ± 1.8 years, mean CCECAI = 3.1 ± 2.2 and signs of GER); and 11 in Group B (mean age 9.8 ± 1.4 years, CCECAI = 0, no signs of GER). Seven (25.9%) of the 27 BSD (Group A 4/16, Group B 3/11) had leukopenia. Serum C-reactive protein tended to be increased with more advanced GC (P = 0.063). Frequency of GC, mucosal atrophy, mucous metaplasia, or glandular dysplasia did not differ between groups. GC was frequently diagnosed (6/27), even without clinical signs (2/11). The odds ratio for vomiting (OR = 9.9; P = 0.016) was increased only when glandular dysplasia was present. GC was associated with mucous metaplasia (P = 0.024) and glandular dysplasia (P = 0.006), but not with mucosal atrophy (P = 1). Conclusions GC can develop as an occult disease, associated with metaplasia and dysplasia of the gastric mucosa. Suggestive clinical signs, notably vomiting, should warrant timely endoscopy in BSD. Extensive endoscopic screening of asymptomatic dogs remains, however, unrealistic. Therefore, biomarkers of mucosal pathology preceding clinical illness are needed to support an indication for endoscopy and enable early diagnosis of GC.
  • Karjalainen, Piia; Santalahti, Päivi; Aronen, Eeva T; Kiviruusu, Olli (BioMed Central, 2021)
    Abstract Background This randomized controlled trial (RCT) evaluated the long-term effectiveness of the Incredible Years® (IY) Parenting Program in modifying children’s externalizing problems among families in Child Protection Services (CPS) and using other special support services. We also examined whether parent-reported effects of the IY® generalize to the daycare/school setting as reported by teachers. Methods Participants in the study were 3–7-year-old children with behavioural problems (N = 102 at baseline, N = 89 at one-year follow-up). Participants were randomized to intervention (N = 50) and control groups (N = 52) after the baseline assessment. The intervention group received 19-week IY® Parenting Program. The effectiveness of the intervention was analyzed using linear mixed model. Results Our previously reported pre-post intervention effects on CBCL (Child Behavior Checklist) and ECBI (Eyberg Child Behavior Inventory) were not sustained to the one-year follow-up. Child conduct problems decreased from baseline to follow-up in both intervention and control groups. The positive changes were not observed at daycare/school from baseline to post-intervention or to the one-year follow-up, and there were no significant differences in changes between the groups. Conclusions Evidence-based parenting program IY® seems to be an effective intervention for child conduct problems in the short term in families in the CPS context, but sustaining the positive effects and generalizing them to the daycare/school context are challenging. Trial registration: The trial is registered in the registry (NCT03239990), Registered August 4th, 2017;
  • Ferrannini, Giulia; De Bacquer, Dirk; Vynckier, Pieter; De Backer, Guy; Gyberg, Viveca; Kotseva, Kornelia; Mellbin, Linda; Norhammar, Anna; Tuomilehto, Jaakko; Wood, David; Rydén, Lars (BioMed Central, 2021)
    Abstract Background Gender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients. Methods The study population (n = 16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012–2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016–2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age. Results Known diabetes was more common among women (32.9%) than men (28.4%, p < 0.0001). OGTT (n = 8655) disclosed IGT in 17.2% of women vs. 15.1% of men (p = 0.004) and diabetes in 13.4% of women vs. 14.6% of men (p = 0.078). In both known diabetes and newly detected dysglycaemia groups, women were older, with higher proportions of hypertension, dyslipidaemia and obesity. HbA1c was higher in women with known diabetes. Recommended targets of physical activity, blood pressure and cholesterol were achieved by significantly lower proportions of women than men. Women with known diabetes had higher risk for the endpoint than men (age-adjusted HR 1.22; 95% CI 1.04–1.43). Conclusions Guideline-recommended risk factor control is poorer in dysglycemic women than men. This may contribute to the worse prognosis in CAD women with known diabetes.
  • Duru, Ilhan C; Bucur, Florentina I; Andreevskaya, Margarita; Nikparvar, Bahareh; Ylinen, Anne; Grigore-Gurgu, Leontina; Rode, Tone M; Crauwels, Peter; Laine, Pia; Paulin, Lars; Løvdal, Trond; Riedel, Christian U; Bar, Nadav; Borda, Daniela; Nicolau, Anca I; Auvinen, Petri (BioMed Central, 2021)
    Abstract Background High-pressure processing (HPP) is a commonly used technique in the food industry to inactivate pathogens, including L. monocytogenes. It has been shown that L. monocytogenes is able to recover from HPP injuries and can start to grow again during long-term cold storage. To date, the gene expression profiling of L. monocytogenes during HPP damage recovery at cooling temperature has not been studied. In order identify key genes that play a role in recovery of the damage caused by HPP treatment, we performed RNA-sequencing (RNA-seq) for two L. monocytogenes strains (barotolerant RO15 and barosensitive ScottA) at nine selected time points (up to 48 h) after treatment with two pressure levels (200 and 400 MPa). Results The results showed that a general stress response was activated by SigB after HPP treatment. In addition, the phosphotransferase system (PTS; mostly fructose-, mannose-, galactitol-, cellobiose-, and ascorbate-specific PTS systems), protein folding, and cobalamin biosynthesis were the most upregulated genes during HPP damage recovery. We observed that cell-division-related genes (divIC, dicIVA, ftsE, and ftsX) were downregulated. By contrast, peptidoglycan-synthesis genes (murG, murC, and pbp2A) were upregulated. This indicates that cell-wall repair occurs as a part of HPP damage recovery. We also observed that prophage genes, including anti-CRISPR genes, were induced by HPP. Interestingly, a large amount of RNA-seq data (up to 85%) was mapped to Rli47, which is a non-coding RNA that is upregulated after HPP. Thus, we predicted that Rli47 plays a role in HPP damage recovery in L. monocytogenes. Moreover, gene-deletion experiments showed that amongst peptidoglycan biosynthesis genes, pbp2A mutants are more sensitive to HPP. Conclusions We identified several genes and mechanisms that may play a role in recovery from HPP damage of L. monocytogenes. Our study contributes to new information on pathogen inactivation by HPP.
  • Wang, Yunsheng; Kukko, Antero; Hyyppä, Eric; Hakala, Teemu; Pyörälä, Jiri; Lehtomäki, Matti; El Issaoui, Aimad; Yu, Xiaowei; Kaartinen, Harri; Liang, Xinlian; Hyyppä, Juha (Springer Singapore, 2021)
    Abstract Background Current automated forest investigation is facing a dilemma over how to achieve high tree- and plot-level completeness while maintaining a high cost and labor efficiency. This study tackles the challenge by exploring a new concept that enables an efficient fusion of aerial and terrestrial perspectives for digitizing and characterizing individual trees in forests through an Unmanned Aerial Vehicle (UAV) that flies above and under canopies in a single operation. The advantage of such concept is that the aerial perspective from the above-canopy UAV and the terrestrial perspective from the under-canopy UAV can be seamlessly integrated in one flight, thus grants the access to simultaneous high completeness, high efficiency, and low cost. Results In the experiment, an approximately 0.5 ha forest was covered in ca. 10 min from takeoff to landing. The GNSS-IMU based positioning supports a geometric accuracy of the produced point cloud that is equivalent to that of the mobile mapping systems, which leads to a 2–4 cm RMSE of the diameter at the breast height estimates, and a 4–7 cm RMSE of the stem curve estimates. Conclusions Results of the experiment suggested that the integrated flight is capable of combining the high completeness of upper canopies from the above-canopy perspective and the high completeness of stems from the terrestrial perspective. Thus, it is a solution to combine the advantages of the terrestrial static, the mobile, and the above-canopy UAV observations, which is a promising step forward to achieve a fully autonomous in situ forest inventory. Future studies should be aimed to further improve the platform positioning, and to automatize the UAV operation.
  • Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Pulkki, Kari; Turkia, Heidi; Sabell, Tuija; Tolppanen, Heli; Jurkko, Raija; Hongisto, Mari; Kataja, Anu; Sionis, Alessandro; Silva-Cardoso, Jose; Banaszewski, Marek; DiSomma, Salvatore; Mebazaa, Alexandre; Haapio, Mikko; Lassus, Johan (Springer International Publishing, 2021)
    Abstract Background Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p < 0.001) and 5.2 (95% CI 2.8–9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. Trial registration: NCT01374867 at , registered 16 Jun 2011—retrospectively registered
  • Dixit, Pragyesh; Kokate, Shrikant B; Poirah, Indrajit; Chakraborty, Debashish; Smoot, Duane T; Ashktorab, Hassan; Rout, Niranjan; Singh, Shivaram P; Bhattacharyya, Asima (BioMed Central, 2021)
    Abstract Background Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression. Methods H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay. Results Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine6 (Ser6) and threonine279 (Thr279). Phosphorylation of Siah2 was mediated by MRCKβ, a Ser/Thr protein kinase. MRCKβ was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKβ could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKβ and use of proteasomal inhibitor MG132 could rescue MRCKβ from Siah2-mediated degradation. Ser6 and Thr279 phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells. Conclusions Increased level of Ser6 and Thr279-phosphorylated-Siah2 and downregulated MRCKβ were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKβ-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.
  • Marttinen, Maiju K; Kautiainen, Hannu; Haanpää, Maija; Pohjankoski, Heini; Hintikka, Jukka; Kauppi, Markku J (BioMed Central, 2021)
    Abstract Background Pain is a frequent and inevitable factor affecting the quality of life among older people. Several studies have highlighted the ineffectiveness of treating chronic pain among the aged population, and little is known about the prevalence of analgesics administration among community-dwelling older adults. The objective was to examine older adults’ prescription analgesic purchases in relation to SF-36 pain in a population-based setting. Methods One thousand four hundred twenty community-dwelling citizens aged 62–86 years self-reported SF-36 bodily pain (pain intensity and pain-related interference) scores for the previous 4 weeks. The Social Insurance Institution of Finland register data on analgesic purchases for 6 months prior to and 6 months after the questionnaire data collection were considered. Special interest was focused on factors related to opioid purchases. Results Of all participants, 84% had purchased prescription analgesics during 1 year. NSAIDs were most frequently purchased (77%), while 41% had purchased paracetamol, 32% opioids, 17% gabapentinoids, and 7% tricyclic antidepressants. Age made no marked difference in purchasing prevalence. The number of morbidities was independently associated with analgesic purchases in all subjects and metabolic syndrome also with opioid purchases in subjects who had not reported any pain. Discussion Substantial NSAID and opioid purchases emerged. The importance of proper pain assessment and individual deliberation in terms of analgesic contraindications and pain quality, as well as non-pharmacological pain management, need to be highlighted in order to optimize older adults’ pain management.
  • Long, Di; Mackenbach, Johan; Martikainen, Pekka; Lundberg, Olle; Brønnum-Hansen, Henrik; Bopp, Matthias; Costa, Giuseppe; Kovács, Katalin; Leinsalu, Mall; Rodríguez-Sanz, Maica; Menvielle, Gwenn; Nusselder, Wilma (BioMed Central, 2021)
    Abstract Purpose To study the trends of smoking-attributable mortality among the low and high educated in consecutive birth cohorts in 11 European countries. Methods Register-based mortality data were collected among adults aged 30 to 79 years in 11 European countries between 1971 and 2012. Smoking-attributable deaths were estimated indirectly from lung cancer mortality rates using the Preston-Glei-Wilmoth method. Rate ratios and rate differences among the low and high-educated were estimated and used to estimate the contribution of inequality in smoking-attributable mortality to inequality in total mortality. Results In most countries, smoking-attributable mortality decreased in consecutive birth cohorts born between 1906 and 1961 among low- and high-educated men and high-educated women, but not among low-educated women among whom it increased. Relative educational inequalities in smoking-attributable mortality increased among both men and women with no signs of turning points. Absolute inequalities were stable among men but slightly increased among women. The contribution of inequality in smoking-attributable mortality to inequality in total mortality decreased in consecutive generations among men but increased among women. Conclusions Smoking might become less important as a driver of inequalities in total mortality among men in the future. However, among women, smoking threatens to further widen inequalities in total mortality.
  • Akujärvi, Anu; Repo, Anna; Akujärvi, Altti M; Liski, Jari (Springer Singapore, 2021)
    Abstract Background Increasing the use of forest harvest residues for bioenergy production reduces greenhouse emissions from the use of fossil fuels. However, it may also reduce carbon stocks and habitats for deadwood dependent species. Consequently, simple tools for assessing the trade-offs of alternative management practices on forest dynamics and their services to people are needed. The objectives of this study were to combine mapping and simulation modelling to investigate the effects of forest management on ecosystem services related to carbon cycle in the case of bioenergy production; and to evaluate the suitability of this approach for assessing ecosystem services at the landscape level. Stand level simulations of forest growth and carbon budget were combined with extensive multi-source forest inventory data across a southern boreal landscape in Finland. Stochastic changes in the stand age class distribution over the study region were simulated to mimic variation in management regimes. Results The mapping framework produced reasonable estimates of the effects of forest management on a set of key ecosystem service indicators: the annual carbon stocks and fluxes of forest biomass and soil, timber and energy-wood production and the coarse woody litter production over a simulation period 2012–2100. Regular harvesting, affecting the stand age class distribution, was a key driver of the carbon stock changes at a landscape level. Extracting forest harvest residues in the final felling caused carbon loss from litter and soil, particularly with combined aboveground residue and stump harvesting. It also reduced the annual coarse woody litter production, demonstrating negative impacts on deadwood abundance and, consequently, forest biodiversity. Conclusions The refined mapping framework was suitable for assessing ecosystem services at the landscape level. The procedure contributes to bridging the gap between ecosystem service mapping and detailed simulation modelling in boreal forests. It allows for visualizing ecosystem services as fine resolution maps to support sustainable land use planning. In the future, more detailed models and a wider variety of ecosystem service indicators could be added to develop the method.

View more