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Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

Boreal forest floor emits biogenic volatile organic compounds (BVOCs) from the understorey vegetation and the heterogeneous soil matrix, where the interactions of soil organisms and soil chemistry are complex. Earlier studies have focused on determining the net exchange of VOCs from the forest floor. This study goes one step further, with the aim of separately determining whether the photosynthesized carbon allocation to soil affects the isoprenoid production by different soil organisms, i.e., decomposers, mycorrhizal fungi, and roots. In each treatment, photosynthesized carbon allocation through roots for decomposers and mycorrhizal fungi was controlled by either preventing root ingrowth (50 µm mesh size) or the ingrowth of roots and fungi (1 µm mesh) into the soil volume, which is called the trenching approach. Isoprenoid fluxes were measured using dynamic (steady-state flow-through) chambers from the different treatments. This study aimed to analyze how important the understorey vegetation is as a VOC sink. Finally, a statistical model was constructed based on prevailing temperature, seasonality, trenching treatments, understory vegetation cover, above canopy photosynthetically active radiation (PAR), soil water content, and soil temperature to estimate isoprenoid fluxes. The final model included parameters with a statistically significant effect on the isoprenoid fluxes. The results show that the boreal forest floor emits monoterpenes, sesquiterpenes, and isoprene. Monoterpenes were the most common group of emitted isoprenoids, and the average flux from the non-trenched forest floor was 23 µg m−2 h−1. The results also show that different biological factors, including litterfall, carbon availability, biological activity in the soil, and physico-chemical processes, such as volatilization and absorption to the surfaces, are important at various times of the year. This study also discovered that understorey vegetation is a strong sink of monoterpenes. The statistical model, based on prevailing temperature, seasonality, vegetation effect, and the interaction of these parameters, explained 43 % of the monoterpene fluxes, and 34–46 % of individual α-pinene, camphene, β-pinene, and Δ3-carene fluxes.

Pyramidal cells in layer V of the neocortex are one of the most widely studied neuron types in the mammalian brain. Due to their role as integrators of feedforward and cortical feedback inputs, they are well-positioned to contribute to the symptoms and pathology in mental disorders—such as schizophrenia—that are characterized by a mismatch between the internal perception and external inputs. In this modeling study, we analyze the input/output properties of layer V pyramidal cells and their sensitivity to modeled genetic variants in schizophrenia-associated genes. We show that the excitability of layer V pyramidal cells and the way they integrate inputs in space and time are altered by many types of variants in ion-channel and Ca2+ transporter-encoding genes that have been identified as risk genes by recent genome-wide association studies. We also show that the variability in the output patterns of spiking and Ca2+ transients in layer V pyramidal cells is altered by these model variants. Importantly, we show that many of the predicted effects are robust to noise and qualitatively similar across different computational models of layer V pyramidal cells. Our modeling framework reveals several aspects of single-neuron excitability that can be linked to known schizophrenia-related phenotypes and existing hypotheses on disease mechanisms. In particular, our models predict that single-cell steady-state firing rate is positively correlated with the coding capacity of the neuron and negatively correlated with the amplitude of a prepulse-mediated adaptation and sensitivity to coincidence of stimuli in the apical dendrite and the perisomatic region of a layer V pyramidal cell. These results help to uncover the voltage-gated ion-channel and Ca2+ transporter-associated genetic underpinnings of schizophrenia phenotypes and biomarkers.

Up until the 1960s and 1970s, diarrhea, malabsorption syndrome, and failure to thrive were the presenting symptoms and signs of celiac disease (CD) in young infants; however this disease was also at the same time reported to be disappearing. Indeed, clinical childhood CD was seen to transform into a milder form, resulting in an upward shift in age at diagnosis during the 1970s (and years later for many countries). This changing pattern of CD presentation then altered the epidemiology of the disease, with major differences between and within countries observed. An awareness of the changing clinical nature of CD and use of case-finding tools to detect even clinically silent CD became an important factor in this changing epidemiology. Countries report both low and high prevalence but it seems to be on the increase resulting in a population-based level of 1–2%. This paper discusses the potential causes and environmental factors behind these observed clinical changes, identifying new clues from different studies published at the time this transformation took place. For instance, it was found that breastfeeding postponed the diagnosis of the disease but did not altogether prevent it. Moreover, gluten introduction at a young age, specifically at the mean age of 2 months, seemed to also have a clear impact in inducing malabsorption syndrome and failure to thrive in young infants in addition to other factors such as gluten intake volume and type of cereal present in the weaning food. Further, the impact of cow's milk and its high osmolarity might have played an important role; humanized milk formulas were not yet invented. Future epidemiological studies on the contributing environmental factors to the shift in CD presentation are thus recommended for countries in which these changing clinical features are still being observed.

The brain is the most complex of human organs, and the pathophysiology underlying abnormal brain function in psychiatric disorders is largely unknown. Despite the rapid development of diagnostic tools and treatments in most areas of medicine, our understanding of mental disorders and their treatment has made limited progress during the last decades. While recent advances in genetics and neuroscience have a large potential, the complexity and multidimensionality of the brain processes hinder the discovery of disease mechanisms that would link genetic findings to clinical symptoms and behavior. This applies also to schizophrenia, for which genome-wide association studies have identified a large number of genetic risk loci, spanning hundreds of genes with diverse functionalities. Importantly, the multitude of the associated variants and their prevalence in the healthy population limit the potential of a reductionist functional genetics approach as a stand-alone solution to discover the disease pathology. In this review, we outline the key concepts of a “biophysical psychiatry,” an approach that employs large-scale mechanistic, biophysics-founded computational modelling to increase transdisciplinary understanding of the pathophysiology and strive toward robust predictions. We discuss recent scientific advances that allow a synthesis of previously disparate fields of psychiatry, neurophysiology, functional genomics, and computational modelling to tackle open questions regarding the pathophysiology of heritable mental disorders. We argue that the complexity of the increasing amount of genetic data exceeds the capabilities of classical experimental assays and requires computational approaches. Biophysical psychiatry, based on modelling diseased brain networks using existing and future knowledge of basic genetic, biochemical, and functional properties on a single neuron to a microcircuit level, may allow a leap forward in deriving interpretable biomarkers and move the field toward novel treatment options.

Oral lesions in the bit area are common in horses, but not comprehensively studied in harness racing horses. This study describes the type and occurrence of oral soft tissue lesions in the area affected by the bit, hereafter called the bit area, in trotters after a race. Based on our results, we suggest a system for scoring lesions according to size, type (bruise or wound), age, and depth (superficial or deep). The data was collected during a welfare program for trotters, conducted by The Finnish Trotting and Breeding Association (Suomen Hippos ry). The rostral part of the mouth of 261 horses (151 Standardbreds, 78 Finnhorses, and 32 ponies) was examined after a race in a systematic manner, using a bright light source without sedation or a mouth gag. The lip commissures (outside and inside), bars of the mandible, buccal area near the second upper premolar teeth, tongue, and hard palate were visually examined; bars of the mandible were also palpated. Points were assigned to every lesion and then added together, such that each horse got an acute lesion score. Based on the score, the horses were divided into four groups (A—D) as follows: Group A, no lesions; B, mild lesions; C, moderate lesions; D, severe lesions. Of all the horses examined, 84% (219/261) had acute lesions in the bit area. In total, 21% (55/261) had mild lesions, 43% (113/261) had moderate lesions, and 20% (51/261) had severe lesions. Visible bleeding outside the mouth was observed in 2% (6/261) of the horses. Further, 5% of the horses (13/261) had blood on the bit when it was removed from the mouth, even though no blood was visible outside the mouth. In conclusion, soft tissue lesions in the bit area were common in the Finnish trotters examined. Moreover, the absence of blood outside the mouth does not rule out serious injuries inside the mouth. The scoring system presented can be used for evaluating the severity of oral lesions in different equestrian disciplines and populations to allow for comparable data across studies.

In the northern hemisphere, boreal forests are a major source of biogenic volatile organic compounds (BVOCs), which drive atmospheric processes and lead to cloud formation and changes in the Earth’s radiation budget. Although forest vegetation is known to be a significant source of BVOCs, the role of soil and the forest floor, and especially interannual variations in fluxes, remains largely unknown due to a lack of long-term measurements. Our aim was to determine the interannual, seasonal and diurnal dynamics of boreal forest floor volatile organic compound (VOC) fluxes and to estimate how much they contribute to ecosystem VOC fluxes. We present here an 8-year data set of forest floor VOC fluxes, measured with three automated chambers connected to the quadrupole proton transfer reaction mass spectrometer (quadrupole PTR-MS). The exceptionally long data set shows that forest floor fluxes were dominated by monoterpenes and methanol, with relatively comparable emission rates between the years. Weekly mean monoterpene fluxes from the forest floor were highest in spring and in autumn (maximum 59 and 86 μg m-2 h-1, respectively), whereas the oxygenated VOC fluxes such as methanol had highest weekly mean fluxes in spring and summer (maximum 24 and 79 μg m-2 h-1, respectively). Although the chamber locations differed from each other in emission rates, the inter-annual dynamics were very similar and systematic. Accounting for this chamber location dependent variability, temperature and relative humidity, a mixed effects linear model was able to explain 79–88% of monoterpene, methanol, acetone, and acetaldehyde fluxes from the boreal forest floor. The boreal forest floor was a significant contributor in the forest stand fluxes, but its importance varies between seasons, being most important in autumn. The forest floor emitted 2–93% of monoterpene fluxes in spring and autumn and 1–72% of methanol fluxes in spring and early summer. The forest floor covered only a few percent of the forest stand fluxes in summer.

Edible insect rearing could provide one alternative for protein production by having a smaller environmental impact than traditional livestock farming due to insects' ability to convert organic side streams. Currently, the insect rearing industry utilizes soybeans as a major source of protein in the feeds. Protein-rich by-products of food industry could be used to replace them in insect feeds, but it is not known if they also meet the insects' nutritional requirements. Our study evaluated the growth performance of two widely used edible cricket species, Acheta domesticus and Gryllus bimaculatus (Orthoptera: Gryllidae), on 18 experimental diets. The experimental diets included commercial chicken feeds and cricket diets, where soybean was partly and completely replaced with by-products from food industry: potato protein, barley mash, barley feed, compressed leftover of turnip rape and mix of broad bean and pea on three levels of protein. We found that the high- and medium-protein turnip rape and barley mash diets produced the highest yield and an increase in all performance variables. Overall, the high- and medium-protein diets produced the highest yield, growth and fastest development. Our results showed that by-products of food industry could be utilized as a part of the cricket feeds and thus advance the goals of circular economy.

Bone metastases are prevalent in many common cancers such as breast, prostate, and lung cancers, and novel therapies for treating bone metastases are needed. Human immune system-engrafted models are used in immuno-oncology (IO) studies for subcutaneous cancer cell or patient-derived xenograft implantations that mimic primary tumor growth. Novel efficacy models for IO compounds on bone metastases need to be established. The study was performed using CIEA NOG (NOG) mice engrafted with human CD34+ hematopoietic stem cells (huNOG) and age-matched immunodeficient NOG mice. Bone phenotyping was performed to evaluate baseline differences. BT-474 human breast cancer cells were inoculated into the tibia bone marrow, and cancer-induced bone changes were monitored by X-ray imaging. Bone content and volume were analyzed by dual X-ray absorptiometry and microcomputed tomography. Tumor-infiltrating lymphocytes (TILs) and the expression of immune checkpoint markers were analyzed by immunohistochemistry. Bone phenotyping showed no differences in bone architecture or volume of the healthy bones in huNOG and NOG mice, but the bone marrow fat was absent in huNOG mice. Fibrotic areas were observed in the bone marrow of some huNOG mice. BT-474 tumors induced osteoblastic bone growth. Bone lesions appeared earlier and were larger, and bone mineral density was higher in huNOG mice. huNOG mice had a high number of human CD3-, CD4-, and CD8-positive T cells and CD20-positive B cells in immune-related organs. A low number of TILs and PD-1-positive cells and low PD-L1 expression were observed in the BT-474 tumors at the endpoint. This study reports characterization of the first breast cancer bone growth model in huNOG mice. BT-474 tumors represent a “cold” tumor with a low number of TILs. This model can be used for evaluating the efficacy of combination treatments of IO therapies with immune-stimulatory compounds or therapeutic approaches on bone metastatic breast cancer.

Osteolytic bone disease is a hallmark of multiple myeloma (MM) mediated by MM cell proliferation, increased osteoclast activity, and suppressed osteoblast function. The proteasome inhibitor bortezomib targets MM cells and improves bone health in MM patients. Radium-223 dichloride (radium-223), the first targeted alpha therapy approved, specifically targets bone metastases, where it disrupts the activity of both tumor cells and tumor-supporting bone cells in mouse models of breast and prostate cancer bone metastasis. We hypothesized that radium-223 and bortezomib combination treatment would have additive effects on MM. In vitro experiments revealed that the combination treatment inhibited MM cell proliferation and demonstrated additive efficacy. In the systemic, syngeneic 5TGM1 mouse MM model, both bortezomib and radium-223 decreased the osteolytic lesion area, and their combination was more effective than either monotherapy alone. Bortezomib decreased the number of osteoclasts at the tumor–bone interface, and the combination therapy resulted in almost complete eradication of osteoclasts. Furthermore, the combination therapy improved the incorporation of radium-223 into MM-bearing bone. Importantly, the combination therapy decreased tumor burden and restored body weights in MM mice. These results suggest that the combination of radium-223 with bortezomib could constitute a novel, effective therapy for MM and, in particular, myeloma bone disease.

The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1, 2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in Hif-p4h-1−/−, Hif-p4h-2 hypomorph and Hif-p4h-3−/− mice. Only Hif-p4h-2 hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs.

This article describes initiatives implemented in Finland to create an online learning environment for studying geographic information systems (GIS). A development project produced an online GIS tool called PaikkaOppi, aimed at promoting GIS studies and spatial thinking skills in upper secondary schools. The project is reviewed through analysis of its technical and pedagogical backgrounds and a description of how it was established and how the pilot phase has been implemented. The article also presents some of the key insights, notes and findings from the first pilot courses.

Purpose: This paper aims to study the visibilization of learning in the context of developing a new collaborative practice, knotworking, in building design. The case under study describes the process of learning from the initiation of knotworking to its experimentation. The implementation of new building information modeling tools acted as an impetus for this development. Design/Methodology/Approach: The research is based on activity-theoretically oriented ethnographic research. The four analytical steps created by Engeström (1999) for analyzing the expansive visibilization of learning are applied in the analysis. Findings: The envisioning of the idea of knotworking involved the first and the second steps of visibilization. First, a flowchart made the ideal process of design visible and triggered a discussion on the problems and requirements emerging in the project members' work. Second, an idea for a new type of collaboration was introduced as a solution to these problems and requirements. Planning the knotworking experiment and explicating the associated design instruments involved the third step of expansive visibilization. The fourth step of visibilization took place during the experiment of knotworking in a design project. Practical Implications: Two other knotworking projects have already been conducted, and plans have been made to commercialize knotworking in building design. New technical tools have been developed for energy calculation and the comparison of alternative design requirements. Social Implications: Knotworking can improve the collaboration between designers with positive implications on the quality of a building design process. Originality/Value: Development and learning are studied as a longitudinal process in the construction industry.

Herein, it has been shown that betulin can be transformed into its biologically active oxo-derivatives (betulone, betulinic and betulonic aldehydes) by liquid-phase oxidation over supported silver catalysts under mild conditions. In order to identify the main factors determining the catalytic behavior of nanosilver catalysts in betulin oxidation, silver was deposited on various alumina supports (γ-alumina and boehmite) using deposition–precipitation with NaOH and incipient wetness impregnation methods, followed by treatment in H2 or O2. Silver catalysts and the corresponding supports were characterized by X-ray diffraction, nitrogen physisorption, inductively coupled plasma optical emission spectroscopy, photoelectron spectroscopy and transmission electron microscopy. It was found that the support nature, preparation and treatment methods predetermine not only the average Ag nanoparticles size and their distribution, but also the selectivity of betulin oxidation, and thereby, the catalytic behavior of Ag catalysts. In fact, the support nature had the most considerable effect. Betulin conversion, depending on the support, increased in the following order: Ag/boehmite < Ag/boehmite (calcined) < Ag/γ-alumina. However, in the same order, the share of side reactions catalyzed by strong Lewis acid centers of the support also increased. Poisoning of the latter by NaOH during catalysts preparation can reduce side reactions. Additionally, it was revealed that the betulin oxidation catalyzed by nanosilver catalysts is a structure-sensitive reaction.

Heavy metal contamination was identified in groundwater monitoring wells surrounding a waste deposit facility at the Rönnskär Cu–Pb–Zn smelter in Skellefteå, Northern Sweden, as well as in brackish water and sediments from the nearby harbor. Following an investigative study of the surrounding area, brackish water from the Baltic Sea and sediments from a nearby harbor were also determined to be contaminated. This study investigated the ranges of isotopic compositions of four elements (Cd, Cu, Pb, and Zn) in smelter materials (ores, products, and waste) and polluted groundwater sediments of the affected area. The study’s objective was to evaluate the variability of the polluting source and identify possible isotope fractionation. This study further assesses the viability of using isotopic information to identify the source of the pollutant. These data were used in combination with multi-element screening analysis and multivariate statistical techniques. Expanding the number of elements utilized in isotope tracing empowers our abilities to decipher the source(s) and the extent of environmental exposure from contamination events related to mining and refining operations.

Abstract Background Regular physical activity (PA) confers many positive effects on health and well-being. Sedentary behavior (SB), in turn, is a risk factor for health, regardless of the level of moderate to vigorous PA. The present study describes the levels of objectively measured SB, breaks in SB, standing still and PA among Finnish adults. Methods This cross-sectional analysis is based on the sub-sample of the population-based Health 2011 Study of Finnish adults. The study population consisted of 18-to-85-year old men and women who wore a waist-worn triaxial accelerometer (Hookie AM 20) for at least 4 days, for at least 10 h per day (n = 1587) during a week. PA and SB were objectively assessed from the raw accelerometric data using novel processing and analysis algorithms with mean amplitude deviation as the processing method. The data was statistically analyzed using cross-tabulations, analysis of variance and analysis of covariance. Results The participants were on average 52 years old, 57 % being women. Participants were sedentary 59 % of their waking wear time, mainly sitting. They spent 17 % of the time standing still, 15 % in light intensity PA, 9 % in moderate PA and less than 1 % in vigorous PA. Participants aged 30–39 years had the highest number of breaks in SB per day. Younger participants (

Abstract Background The current political agenda aims to promote active environments and physical activity while commuting to work, but research on it has provided mixed results. This study examines whether the proximity of green space and people’s residence in different travel-related urban zones contributes to commuting physical activity. Methods Population-based cross-sectional health examination survey, Health 2011 study, and geographical information system (GIS) data were utilized. The GIS data on green space and travel-related urban zones were linked to the individuals of the Health 2011 study, based on their home geocoordinates. Commuting physical activity was self-reported. Logistic regression models were applied, and age, gender, education, leisure-time and occupational physical activity were adjusted. Analyses were limited to those of working age, living in the core-urban areas of Finland and having completed information on commuting physical activity (n = 2 098). Results Home location in a pedestrian zone of a main centre (odds ratio = 1.63; 95 % confidence interval = 1.06–2.51) or a pedestrian zone of a sub-centre (2.03; 1.09–3.80) and higher proportion of cycling and pedestrian networks (3.28; 1.71–6.31) contributed to higher levels of commuting physical activity. The contribution remained after adjusting for all the environmental attributes and individuals. Based on interaction analyses, women living in a public transport zone were almost two times more likely to be physically active while commuting compared to men. A high proportion of recreational green space contributed negatively to the levels of commuting physical activity (0.73; 0.57–0.94) after adjusting for several background factors. Based on interaction analyses, individuals aged from 44 to 54 years and living in sub-centres, men living in pedestrian zones of sub-centres, and those individuals who are physically inactive during leisure-time were less likely to be physically active while commuting. Conclusions Good pedestrian and cycling infrastructure may play an important role in promoting commuting physical activity among the employed population, regardless of educational background, leisure-time and occupational physical activity. Close proximity to green space and a high proportion of green space near the home may not be sufficient to initiate commuting physical activity in Finland, where homes surrounded by green areas are often situated in car-oriented zones far from work places.

Background: We evaluated the prevalence of psychiatric disorders in mild traumatic brain injury (MTBI) patients and investigated psychiatric comorbidity in relation to subjective symptoms and return to work (RTW). Methods: We recruited 103 MTBI patients (mean age 40.8 years, SD 3.1) prospectively from University Hospital. The patients were followed up for one year. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) and Extended Glasgow Outcome Scale (GOSE) were administered one month after MTBI. Three months after MTBI, any psychiatric disorders were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Psychiatric disorders were diagnosed in 26 patients (25.2%). The most common disorders were previous/current depression. At three months, there was no difference between patients with psychiatric disorders versus those without them in RTW (95.7% vs. 87.3%, p = 0.260) or at least in part-time work (100% vs. 94.4%, p = 0.245). In Kaplan–Meier analysis, the median time to RTW was 10 days for both groups. The median RPQ score was 13.0 (Interquartile range (IQR) 6.5–19.0) in patients with a psychiatric disorder compared to 8.5 (IQR 2.3–14.0) in those without one (p = 0.021); respectively, the median GOSE was 7.0 (IQR 7.0–8.0) compared to 8.0 (IQR 7.0–8.0, p = 0.003). Conclusions: Approximately every fourth patient with MTBI had a psychiatric disorder. These patients reported more symptoms, and their functional outcome measured with GOSE at one month after MTBI was worse. However, presence of any psychiatric disorder did not affect RTW. Early contact and adequate follow-up are important when supporting the patient’s return to work.

Rodents are known to be reservoir hosts for a plethora of zoonotic viruses and therefore play a significant role in the dissemination of these pathogens. We trapped three vole species (Microtus arvalis, Alexandromys oeconomus and Microtus agrestis) in northeastern Poland, all of which are widely distributed species in Europe. Using immunofluorescence assays, we assessed serum samples for the presence of antibodies to hantaviruses, arenaviruses and cowpox viruses (CPXV). We detected antibodies against CPXV and Puumala hantavirus (PUUV), the overall seroprevalence of combined viral infections being 18.2% [10.5–29.3] and mostly attributed to CPXV. We detected only one PUUV/TULV cross-reaction in Microtus arvalis (1.3% [0.1–7.9]), but found similar levels of antibodies against CPXV in all three vole species. There were no significant differences in seroprevalence of CPXV among host species and age categories, nor between the sexes. These results contribute to our understanding of the distribution and abundance of CPXV in voles in Europe, and confirm that CPXV circulates also in Microtus and Alexandromys voles in northeastern Poland.

Developing shoots, i.e., sprouts, and older needles of Norway spruce (Picea abies (L.) Karst.) have traditionally been used for medicinal purposes due to the high content of vitamins and antioxidants. Currently, sprouts are available as, for example, superfood and supplements. However, end-product quality and nutritive value may decline in the value-chain from raw material sourcing to processing and storage. We studied (1) impacts of different drying and extraction methods on nutritional composition and antioxidative properties of sprouts and needles, (2) differences between sprouts and needles in nutritional composition and microbiological quality, and (3) production scale quality of the sprouts. Additionally, (4) sprout powder was applied in products (ice-cream and sorbet) and consumer acceptance was evaluated. According to our results, older needles have higher content of dry matter, energy, and calcium, but lower microbial quality than sprouts. Sprouts showed a higher concentration of vitamin C, magnesium, potassium, and phosphorus than older needles. Freeze-drying was the best drying method preserving the quality of both sprouts and needles, e.g., vitamin C content. The antioxidative activity of the sprout extracts were lower than that of needles. Ethanol-water extraction resulted in a higher content of active compounds in the extract than water extraction. Sensory evaluation of food products revealed that on average, 76% of consumers considered sprout-containing products very good or good, and a creamy product was preferred over a water-based sorbet.

The aim of this study was to find new sustainable, Nordic natural antioxidant sources, develop subcritical water extraction (SWE) process for recovering the antioxidant compounds from the most potential raw materials, and to test their antioxidative effects in meat products. The antioxidant capacities of water and 50% ethanol (aq) extracts of 13 berry, grain, and horticultural plant materials as well as hexane/ethanol extracted stilbene fractions from pine heartwood and spruce inner bark were measured in hydrophilic and lipophilic systems. Tree, bilberry leaf (BL), and sea buckthorn leaf (SBL) extracts showed the highest antioxidant capacities. BL and SBL were selected for the development of SWE. The optimal conditions for recovering maximal antioxidative capacities were 110 °C/1 min for SBL and 120 °C/1 min for BL. Dried BL and SBL and the respective optimized subcritical water extracts were applied in chicken slices and pork sausage, and their ability to prevent lipid oxidation was evaluated during 8 and 20 days storage, respectively, at 6 °C. All tested plant ingredients effectively prevented lipid oxidation in the products compared to the control samples. Sensory acceptance of the plant ingredients was good, especially in the chicken product. To our knowledge, this is the first study to assess the antioxidant effects of SW extracted berry leaves in meat products.

Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.

Volatile organic compounds (VOCs) play an essential role in climate change and air pollution by modulating tropospheric oxidation capacity and providing precursors for ozone and aerosol formation. Arctic permafrost buries large quantities of frozen soil carbon, which could be released as VOCs with permafrost thawing or collapsing as a consequence of global warming. However, due to the lack of reported studies in this field and the limited capability of the conventional measurement techniques, it is poorly understood how much VOCs could be emitted from thawing permafrost and the chemical speciation of the released VOCs. Here we apply a Vocus proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF) in laboratory incubations for the first time to examine the release of VOCs from thawing permafrost peatland soils sampled from Finnish Lapland. The warming-induced rapid VOC emissions from the thawing soils were mainly attributed to the direct release of old, trapped gases from the permafrost. The average VOC fluxes from thawing permafrost were four times as high as those from the active layer (the top layer of soil in permafrost terrain). The emissions of less volatile compounds, i.e. sesquiterpenes and diterpenes, increased substantially with rising temperatures. Results in this study demonstrate the potential for substantive VOC releases from thawing permafrost. We anticipate that future global warming could stimulate VOC emissions from the Arctic permafrost, which may significantly influence the Arctic atmospheric chemistry and climate change.

Indirect work of school psychologists has not actualized itself widely in everyday practices. To understand this contradiction, the working environment of school psychologists, that is, the school, is worthy of closer examination. In the present study, we wanted to find out which factors affect school professionals' perceptions of school psychologists' functions. School professionals (teachers, principals, school nurses, and physicians) in 67 regular education schools in Finland filled in a questionnaire. To examine how the various characteristics of schools and school professionals predict differences in perceptions, we used multilevel regression modeling. School professionals consider almost every function of school psychologists rather important--school-level work least so. The perceptions of various professional groups, especially principals, special education teachers, school nurses, and classroom teachers, differed from each other. In addition, the amount of personal cooperation with the school psychologist was positively related with the perceptions of the importance of assessment, consultative, and school-level functions. The school-level findings revealed that the general amount of school psychological service in the school received was negatively related to the perceived importance of therapy function. The extent to which psychologists and school administration are advocates for indirect functions of school psychologist is one potential topic for further research.

Lasten oikeudet sairaalassa pohjautuvat YK:n lapsen oikeuksien julistukseen. Lapsen oi-keudet sairaalassa vahvistavat lapsen osallisuutta omaan hoitoonsa ja terveydenhuollon yksilöllisempää palvelukulttuuria. Opinnäytetyön tarkoituksena oli kuvata, miten lasten oikeuksia kunnioitetaan terveyttä edistävässä sairaalassa. Tavoitteena oli arvioida lasten oikeuksien kunnioittamista kansainvälisen arviointimittarin avulla hoitohenkilökunnan näkökulmasta. Opinnäytetyössä käytetty itsearvioinnin mittari The Self-Evaluation Model and Tool for respect in children (SEMT) on kehitetty vuonna 2004 alkaneen kansainväli-sen tutkimuksen tuloksena. Opinnäytetyö toteutettiin määrällisenä tutkimuksena. Aineis-to kerättiin Keski-Suomen Keskussairaalan lasten vastuualueelta lääkäreiltä ja hoitohenki-lökunnalta sähköisellä kyselykaavakkeella Webropol-ohjelmalla. Keskeisiä kehittämistarpeita kyselyyn vastanneiden mielestä olivat tarve lisäkoulutukselle ja suunnitelmalle lasten oikeuksien tiettyjen osa-alueiden (kuten tasapuolisen hoitoon pääsyn ja lastensuojelullisten toimien) toteutumisen jatkuvasta arvioinnista. Koulutusta kaivattiin standardeihin lapsen oikeuksista sairaalassa, monikulttuuriseen hoitotyöhön, leikin hyödyntämiseen hoito- ja tutkimustilanteissa sekä kuolevan lapsen kohtaamiseen ja kivun hoitoon. Lapsen iän ja kehitystason mukaisen tietoisen suostumuksen huomioi-miseen koettiin tarvetta toimintaohjeille. Toimintaohjeiden kautta lapsen osallisuus voi vahvistua. Lapsen osallisuuden lisääminen yksiköiden toiminnan ja palvelun kehittämi-sessä koettiin myös tärkeäksi. Organisaation sitoutuminen lasten oikeuksiin tulisi olla näkyvämpää, mm. lapsille jaettavan materiaalin ja oikeuksien esillä olemisen kautta. Olennaiseksi koettiin organisaation sitoutuminen periaatteisiin sekä jatkuva arviointi ja laadunhallinta organisaation sisällä. Opinnäytetyön tuloksia voidaan hyödyntää kehitet-täessä sairaalan perhehoitotyötä ja lapsen oikeuksien toteutumista sairaalan yksiköissä.

Artikkelissa tarkastellaan suomalaisen koulunkäynnin muutoksia viimeisen 80 vuoden aikana yhdestä suvusta kootun muisteluaineiston kautta ja avulla. Muisteluaineisto nostaa esille yksityiskohtaisia ja arkisia, muistelijoilleen merkityksellisiä asioita koulunkäyntiin, koulumatkoihin ja kaverisuhteisiin liittyen. Kouluaika näyttäytyy aineistossa nostalgisen muistelun, koulukurin ja ahkeruuden ihanteiden sekä koululaisten omaa toimijuutta korostavan muistelun kautta. Suomalaisen koulujärjestelmän muutokset tulevat muisteluaineistossa näkyväksi muistelijoiden omakohtaisten kokemusten sekä yhdessä muistelun metodologisissa konteksteissa. Kouluaikojen ja koulukulttuurin muisteleminen oli osa jokaisen suvun jäsenen jaettua kokemusmaailmaa, mikä koettiin monipaikkaista sukua yhdistävänä tekijänä koko muisteluprosessissa.

Health and medicine are key areas of sociological specialization, but in the face of rapid global challenges, they are changing. The need for change is becoming more and more urgent and the relevance of some of the traditional approaches, frameworks and theoretical perspectives should be evaluated. The aim of this article is to reflect on this issue and to explore what could be done in response to scientific and societal developments. We argue that more innovative approaches and better research questions would guide us to be more responsive as medical sociologists. In particular, we think that interdisciplinary and translative work hold untapped potentials for our field.

BackgroundCardiovascular disease is a major cause of morbidity and mortality in COPD patients. Systemic inflammation associated with COPD, is often hypothesised as a causal factor. p38 mitogen-activated protein kinases play a key role in the inflammatory pathogenesis of COPD and atherosclerosis.ObjectivesThis study sought to evaluate the effects of losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on vascular inflammation and endothelial function in chronic obstructive pulmonary disease (COPD) patients with systemic inflammation (defined by plasma fibrinogen >2·8g/l).MethodsThis was a randomised, double-blind, placebo-controlled, Phase II trial that recruited COPD patients with plasma fibrinogen >2.8g/l. Participants were randomly assigned by an online program to losmapimod 7·5mg or placebo tablets twice daily for 16 weeks. Pre- and post-dose 18F-Fluorodeoxyglucose positron emission tomography co-registered with computed tomography (FDG PET/CT) imaging of the aorta and carotid arteries was performed to quantify arterial inflammation, defined by the tissue-to-blood ratio (TBR) from scan images. Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD).ResultsWe screened 160 patients, of whom, 36 and 37 were randomised to losmapimod or placebo. The treatment effect of losmapimod compared to placebo was not significant, at -0·05 for TBR (95% CI: -0·17, 0·07), p = 0·42, and +0·40% for FMD (95% CI: -1·66, 2·47), p = 0·70. The frequency of adverse events reported was similar in both treatment groups.ConclusionsIn this plasma fibrinogen-enriched study, losmapimod had no effect on arterial inflammation and endothelial function at 16 weeks of treatment, although it was well tolerated with no significant safety concerns. These findings do not support the concept that losmapimod is an effective treatment for the adverse cardiovascular manifestations of COPD.

Several studies have found that the loss of a child is associated with psychiatric health problems, yet few studies examined whether child loss influences psychotropic medication use. This study examined short- and long-term use of psychotropic medication, both before and after the death of a child, and its potential effect modifiers.A random sample of 205,456 parents, including 902 bereaved parents, were selected from a Finnish total population registry. The analyses were based on linear regressions using generalised estimation equations (GEE) and adjusted for sociodemographic factors. Annual psychotropic use was defined as having purchased prescribed psychotropic medication between 1996 and2012. Bereaved parents were followed for four years prior to and up to four years after the death of their child. An increase in the use of antidepressants and anxiolytics was found in parents following their loss. The highest percentage of use was found around one year after bereavement, followed by a steady decrease although this remained higher than the level of use among non-bereaved four years after the death. Between 20-25% of bereaved mothers and 10-15% of bereaved fathers used antidepressants or anxiolytics one year after bereavement while the corresponding number in non-bereaved was 5-10%. An increase in psychotropic medication was also found several years before the disease-related loss of a child.The use of psychotropic medication is markedly higher among parents after losing a child. Patterns of use leading up to and following the death of a child should be further examined in relation to clinical risk factors so as to identify at risk populations.Bereavement, child death, psychotropic medication, death, child, register, Finland.

Modern society is facing great challenges due to pollution and increased carbon dioxide (CO2) emissions. As part of solving these challenges, the use of renewable energy sources and electric vehicles (EVs) is rapidly increasing. However, increased dynamics have triggered problems in balancing energy supply and consumption demand in the power systems. The resulting uncertainty and unpredictability of energy production, consumption, and management of peak loads has caused an increase in costs for energy market actors. Therefore, the means for studying the balancing of local smart grids with EVs is a starting point for this paper. The main contribution is a simulation-based approach which was developed to enable the study of the balancing of local distribution grids with EV batteries in a cost-efficient manner. The simulation-based approach is applied to enable the execution of a distributed system with the simulation of a local distribution grid, including a number of charging stations and EVs. A simulation system has been constructed to support the simulation-based approach. The evaluation has been carried out by executing the scenario related to balancing local distribution grids with EV batteries in a step-by-step manner. The evaluation results indicate that the simulation-based approach is able to facilitate the evaluation of smart grid– and EV-related communication protocols, control algorithms for charging, and functionalities of local distribution grids as part of a complex, critical cyber-physical system. In addition, the simulation system is able to incorporate advanced methods for monitoring, controlling, tracking, and modeling behavior. The simulation model of the local distribution grid can be executed with the smart control of charging and discharging powers of the EVs according to the load situation in the local distribution grid. The resulting simulation system can be applied to the study of balancing local smart grids with EV batteries. Based on the evaluation results, it is estimated that the simulation-based approach can provide an essential, safe, and cost-efficient method for the evaluation of complex, critical cyber-physical systems, such as smart grids.

Sample barcoding facilitates the analysis of tens or even hundreds of samples in a single next-generation sequencing (NGS) run, but more efficient methods are needed for high-throughput barcoding and size-trimming of long PCR products. Here we present a two-step PCR approach for barcoding followed by pool shearing, adapter ligation, and 5′ end selection for trimming sets of DNA templates of any size. Our new trimming method offers clear benefits for phylogenetic studies, since targeting exactly the same region maximizes the alignment and enables the use of operational taxonomic unit (OTU)-based algorithms.

Phytoplankton is the basis for aquatic food webs and mirrors the water quality. Conventionally, phytoplankton analysis has been done using time consuming and partly subjective microscopic observations, but next generation sequencing (NGS) technologies provide promising potential for rapid automated examination of environmental samples. Because many phytoplankton species have tough cell walls, methods for cell lysis and DNA or RNA isolation need to be efficient to allow unbiased nucleic acid retrieval. Here, we analyzed how two phytoplankton preservation methods, three commercial DNA extraction kits and their improvements, three RNA extraction methods, and two data analysis procedures affected the results of the NGS analysis. A mock community was pooled from phytoplankton species with variation in nucleus size and cell wall hardness. Although the study showed potential for studying Lugol-preserved sample collections, it demonstrated critical challenges in the DNA-based phytoplankton analysis in overall. The 18S rRNA gene sequencing output was highly affected by the variation in the rRNA gene copy numbers per cell, while sample preservation and nucleic acid extraction methods formed another source of variation. At the top, sequence-specific variation in the data quality introduced unexpected bioinformatics bias when the sliding-window method was used for the quality trimming of the Ion Torrent data. While DNA-based analyses did not correlate with biomasses or cell numbers of the mock community, rRNA-based analyses were less affected by different RNA extraction procedures and had better match with the biomasses, dry weight and carbon contents, and are therefore recommended for quantitative phytoplankton analyses.

The Saami are the only indigenous population in Europe and their traditional living area is northern Scandinavia. Hearing impairment (HI) among Saami has not been studied before. The objective was to investigate the presence and type of HI among Saami adults, aged 49–77 years (median age 61 years), living in northern Finland. In addition, the presence of self-reported hearing difficulties, difficulties to hear in background noise and tinnitus were studied. An epidemiological, cross-sectional study encompassing a structured interview, otological examination and audiometry was performed. Bilateral HI was present in 42.9% of men and 29.4% of women, when HI was defined as a pure tone average (PTA) of at least 20 dB hearing level (HL) or more at the frequencies of 0.5, 1, 2 and 4 kHz. In one or both ears (worse ear hearing level, WEHL0.5,1,2,4≥20 dB HL) HI was present in 61.8% of men and 42.2% of women. Sensorineural high frequency hearing impairment was found to be most common. Nearly half (46.9%) of the study subjects reported hearing problems and more than half (55.6%) reported difficulties in following conversation in background noise. Measured HI and subjective hearing difficulties are common among the Saami adults. The healthcare personnel working in this area should be aware of the hearing problems of the Saami population. Abbreviations: ARHI, Age-related hearing impairment; PTA, Pure tone average; HI, Hearing impairment; HL, Hearing level; BEHL, Better ear hearing level; WEHL, Worse ear hearing level; CI, Confidence interval

The unemployed more often suffer from depression than the employed. We examined whether mental health deterioration occurs already before unemployment implicating health selection, or whether it mostly occurs after becoming exposed to the experience rendering causal explanations more likely.We used nationally representative Finnish register data to examine changes in depressive morbidity as measured by antidepressant medication in 1995-2009 over four years before and since a new onset of unemployment (N = 28 000) at the age of 30-60 compared to the employed (N = 124 136). We examined separately those who became continuously long-term unemployed, intermittently unemployed and unemployed with eventual re-employment in the second, third or fourth year since the year of onset. Annual repeated measurements were analysed using generalised estimation equations.Among the employed antidepressant medication increased slowly but steadily over the study period and it was mainly at a lower level than among the unemployed. In the four years leading to unemployment there was excess increase in medication that was generally stronger among those with longer duration of the eventual unemployment experience. During unemployment medication decreased in all groups except among the intermittently unemployed. By the first year of re-employment antidepressant medication reached a level similar to that among the employed and afterwards followed no consistent trend.The associations of unemployment and re-employment with depressive morbidity appear to be largely driven by health selection. The question of potential causal associations remains unresolved for intermittent unemployment in particular.

In the search for novel anticancer drugs, the potassium channel KV10.1 has emerged as an interesting cancer target. Here, we report a new group of KV10.1 inhibitors, namely the purpurealidin analogs. These alkaloids are produced by the Verongida sponges and are known for their wide variety of bioactivities. In this study, we describe the synthesis and characterization of 27 purpurealidin analogs. Structurally, bromine substituents at the central phenyl ring and a methoxy group at the distal phenyl ring seem to enhance the activity on KV10.1. The mechanism of action of the most potent analog 5 was investigated. A shift of the activation curve to more negative potentials and an apparent inactivation was observed. Since KV10.1 inhibitors can be interesting anticancer drug lead compounds, the effect of 5 was evaluated on cancerous and non-cancerous cell lines. Compound 5 showed to be cytotoxic and appeared to induce apoptosis in all the evaluated cell lines.