Aims
Salmonella infections are significant causes of foodborne outbreaks in the European Union. This study investigates a sudden increase in gastroenteritis patients in the hospital district of ...Central Finland in June 2021. The primary aim was to study the outbreak's magnitude and source of the outbreak.
Methods and Results
Epidemiological, microbiological, environmental and traceback investigations were conducted. Over 700 persons fell ill during the outbreak caused by Salmonella Typhimurium associated with a daycare lunch. Similar S. Typhimurium was found in the patients and a vegetable mix containing iceberg lettuce, cucumber and peas served during lunch. The traceback investigation revealed that the batch information of vegetables from the wholesaler was not complete. The wholesaler had received quality complaints about the iceberg lettuce from the central kitchen. The manufacturer did not test the suspected batch for Salmonella since the production plant had given a certificate declaring it Salmonella negative.
Conclusions
The most suspect ingredient was one batch of iceberg lettuce due to quality complaints. The lettuce had not been served in two daycare centres without cases. We recommend that in order to enable thorough microbiological investigation, institutional kitchens store the food samples separately as part of the internal quality control and that food items should always be tested when Salmonella contamination in an outbreak is suspected.
The purpose of this study was to describe what is known about HIV infection and other sexually transmitted diseases, infection transmission routes, care, and sources of information, from the ...viewpoint of men having sex with men.
National data (n = 2,072) was collected from June to August 2010 in Finland as part of a joint internet-based survey conducted in 38 countries (EMIS, European MSM Internet Sex Survey).
The respondents' age, place of residence, highest education and employment status were statistically significantly related to how often the respondent sought information on HIV, testing and treatments, and what they knew about infection transmission routes. The respondents' information seeking behavior was not seen as active regarding HIV infection and other sexually transmitted diseases.
We should also consider the possibility of using internet-based interventions, especially in smaller and northern catchment areas, in order to improve the knowledge level of men having sex with men.
Neglecting to provide older people with the care they need in residential care settings leads to human suffering and increased service needs. Research is lacking on neglect in older people's ...residential care and one way to assess the key issues is to study complaints. The aim of this study was to analyse official complaints related to allegations of neglect in residential care settings caring for older people in Finland. The data covered 317 complaints that were recorded in the national database in 2018 and 2019. The analysis of the complaints yielded 2,922 observations of neglect in older people's care in residential care settings. Based on our results, most of the complaints were made by family members when the patients were alive and their motivation was to improve the care their relative received, as well as the care of others, in the residential care home. The complaints focused on neglecting clinical care, including restricting older people's movements, not providing daily activities and not paying sufficient attention to their hygiene and secretions. Other complaints included issues relating to nutrition, medication, communication and issues that compromised their privacy, respect and dignity. Nearly three of four complaints identified staffing issues in relation to neglect and most of the complaints concerned private, rather than public, residential care homes. Although the complaints only concerned a small proportion of the annual care provided, more attention should be paid to care practices that prevent neglect in residential care and to multi‐level monitoring for dignified care.
Abstract
Soil RNA and DNA were coextracted along a contamination gradient at a landfarming field with aged crude oil contamination to investigate pollution-dependent differences in 16S rRNA and rRNA ...gene pools. Microbial biomass correlated with nucleic acid yields as well as bacterial community change, indicating that the same factors controlled community size and structure. In surface soil, bacterial community evenness, estimated through length heterogeneity PCR (LH-PCR) fingerprinting, appeared higher for RNA-based than for DNA-based communities. The RNA-based community profiles resembled the DNA-based communities of soil with a lower contamination level. Cloning-based identification of bacterial hydrocarbon-degrading taxa in the RNA pool, representing the viable community with high protein synthesis potential, indicated that decontamination processes still continue. Analyses of archaea revealed that only Thaumarchaeota were present in the aerobic samples, whereas more diverse communities were found in the compacted subsurface soil with more crude oil. For subsurface bacteria, hydrocarbon concentration explained neither the community structure nor the difference between RNA-based and DNA-based communities. However, rRNA of bacterial taxa associated with syntrophic and sulphate-reducing alkane degradation was detected. Although the same prokaryotic taxa were identified in DNA and RNA, comparison of the two nucleic acid pools can aid in the assessment of past and future restoration success.
Combined profiling and identification of prokaryotic communities based on both rRNA genes and rRNA provided added value for the assessment of long-term contaminated soil restoration success.
Combined profiling and identification of prokaryotic communities based on both rRNA genes and rRNA provided added value for the assessment of long-term contaminated soil restoration success.
Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed.
We characterized ...the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate FDR <0.25).
This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-30% of breast cancers but has low expression in normal tissue, making it attractive for targeted alpha therapy (TAT). ...HER2-positive breast cancer typically metastasizes to bone, resulting in incurable disease and significant morbidity and mortality. Therefore, new strategies for HER2-targeting therapy are needed. Here, we present the preclinical in vitro and in vivo characterization of the HER2-targeted thorium-227 conjugate (HER2-TTC) TAT in various HER2-positive cancer models. In vitro, HER2-TTC showed potent cytotoxicity in various HER2-expressing cancer cell lines and increased DNA double strand break formation and the induction of cell cycle arrest in BT-474 cells. In vivo, HER2-TTC demonstrated dose-dependent antitumor efficacy in subcutaneous xenograft models. Notably, HER2-TTC also inhibited intratibial tumor growth and tumor-induced abnormal bone formation in an intratibial BT-474 mouse model that mimics breast cancer metastasized to bone. Furthermore, a match in HER2 expression levels between primary breast tumor and matched bone metastases samples from breast cancer patients was observed. These results demonstrate proof-of-concept for TAT in the treatment of patients with HER2-positive breast cancer, including cases where the tumor has metastasized to bone.
The aim of this study was to examine the views of key experts on developing and using cost-effectiveness calculators to plan and evaluate health and wellbeing promotion interventions in health and ...social services. Data for this qualitative interview study were collected from 14 Finnish experts in health and wellbeing coordination, health and social service management and research and health economics in spring 2021. A semi-structured interview method with thematic analysis was used. The experts said that there is a need for cost-effectiveness evaluation tools that support local evidence-based decision-making. This would enable organizations to plan and allocate scarce resources for interventions that promote equitable and effective health and wellbeing. However, practical tools and calculators that enable users to make decisions based on the best available evidence are not widely used. Local decision-makers, researchers and service providers all need to be involved in agreeing goals and selecting the right target groups and measures. They also need to make decisions about the best available data sources and how to use calculators to define and evaluate outcomes. Cost-effectiveness calculators are needed for local evidence-based decision-making, so that municipalities can allocate scarce resources to effective services that increase the wellbeing and equality of residents. This requires key stakeholders to work together to plan, develop and evaluate comprehensive, easy-to-use cost-effectiveness calculators.
To evaluate the biocompatibility of a new muraglitazar-eluting polylactide copolymer stent and investigate its ability to prevent the formation of intimal hyperplasia.
Ten self-expandable ...muraglitazar-eluting poly-96 L/4D-lactic acid (PLA96) stents and 10 self-expandable control PLA96 stents were implanted into porcine common iliac arteries. After 28 days follow-up, all stent-implanted iliac arteries were harvested and prepared for quantitative histomorphometric analysis.
Angiographic analysis revealed that one control PLA96 stent had occluded and one had migrated. Histomorphometric analysis demonstrated that, with the control PLA96 stent, the luminal diameter and area were decreased versus the muraglitazar-eluting PLA96 stents (means ± standard error of the mean, 3.58 mm ± 0.34 vs 4.16 mm ± 0.14 and 9.83 mm(2) ± 2.41 vs 13.75 mm(2) ± 0.93, respectively). The control PLA96 stent induced more intimal hyperplasia than the bioactive muraglitazar-eluting PLA96 stent (557 µm ± 122 vs 361 µm ± 32). Vascular injury scores demonstrated only mild vascular trauma for both stents (muraglitazar-eluting, 0.68 ± 0.07; control, 0.75 ± 0.08). Inflammation scores also showed mild inflammation for both stents (muraglitazar-eluting, 1.05 ± 0.17; control, 1.23 ± 0.19).
This new muraglitazar-eluting PLA96 stent was shown to be biocompatible with a tendency for better patency and less intimal hyperplasia compared with the control PLA96 stents.
Radium-223 dichloride (radium-223, Xofigo®), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer with bone metastases. It is a ...calcium-mimetic that binds to hydroxyapatite in the bone and targets areas of increased bone turnover surrounding cancer lesions. It has been shown that osteoblasts incorporate Radium-223 into the bone matrix in vitro . Radium-223 inhibits disease progression by reducing tumor growth and tumor-induced pathological bone reaction in breast and prostate cancer mouse models. Multiple myeloma (MM) is a plasma-cell malignancy characterized by increased osteoclast and reduced or no osteoblast activity. Bortezomib (Velcade®), an approved treatment for MM, restores the impaired osteoblast activity in MM. Lenalidomide (Revlimid®) induces apoptosis in MM cells and disrupts the interaction between the myeloma cell and its microenvironment. Here, we report results including the effects of radium-223, bortezomib and their combination on mouse MM 5TGM1 cell proliferation in vitro . Furthermore, the anti-tumor effect of the combination of radium-223 with either bortezomib or lenalidomide on the bone lesions and tumor burden in the syngeneic 5TGM1 mouse MM model has been evaluated.
Proliferation assays were performed with the mouse MM 5TGM1 cells using CellTiter-Glo® Luminescent Cell Viability Assay. In vivo experiments were performed in the syngeneic 5TGM1 mouse MM model. This model recapitulates many features of human MM including monoclonal paraprotein as well as pronounced osteolytic bone lesions. In the combination study radium-223 and bortezomib, female 7-week-old C57BL/KaLwRij mice (n=15/group) were inoculated with 5TGM1 cells via tail vein. The administration of radium-223 (300 kBq/kg, single i.v. injection) and/or bortezomib (1 mg/kg i.p., twice a week) or vehicle control was initiated 26 days later. In addition, the effect of the combination of radium-223 and lenalidomide was tested in a separate experiment using an early therapeutic setting in the syngeneic 5TGM1 MM model. The development of osteolytic lesions was monitored by radiography. Tumor cell apoptosis and necrosis were analyzed in histological samples of the hind limbs. TRACP-stained osteoclasts were counted at the tumor-bone interface. Hind limbs were also used for total activity measurement performed by a gamma-counter. The whole-body anti-tumor effect was determined measuring paraprotein (IgG2b) concentration in serum samples in the in vivo studies.
Radium-223 inhibited proliferation of 5TGM1 cancer cells at 800 Bq/ml and bortezomib at 25 nM concentrations. Combination of radium-223 with bortezomib showed increased inhibition of cell proliferation in vitro . The 5TGM1 in vivo model demonstrated that both bortezomib and radium-223 decreased the tumor-induced osteolytic bone lesion area as monotherapy (p<0.05 and p<0.01, respectively), with the combination being more effective than either monotherapy alone (p<0.001). Bortezomib decreased the number of osteoclasts at the tumor-bone interface (p<0.05) and an additive decrease was observed with combination therapy with radium-223 (p<0.01) resulting in almost complete eradication of osteoclasts. The number of apoptotic cells was increased in the radium-223 group, and an increase of necrotic area was observed in the combination group of radium-223 and bortezomib. Tumor burden was lower in groups receiving either bortezomib or bortezomib and radium-223 combination as determined by serum paraprotein (IgG2b). Incorporation of radium-223 to bone was higher with combination therapy based on total activity measurements. All treatments were well tolerated in terms of fatal toxicities, cachexia and body weight loss.
In conclusion, radium-223 therapy in combination with bortezomib decreased the osteolytic lesion area, tumor burden and almost completely eradicated tumor-associated osteoclasts in the 5TGM1 mouse model of myeloma bone disease. The incorporation of radium-223 to bone matrix around tumor lesions was improved, possibly via induction of osteoblast activity by bortezomib. These data provide a strong rationale for combination of radium-223 and bortezomib as possible effective therapy in MM. This is currently investigated in a Phase Ib/II trial in patients with early relapsed MM (NCT02928029).
Suominen:Pharmatest Services Ltd.: Employment, Equity Ownership. Kähkönen:Pharmatest Services Ltd.: Employment. Mäki-Jouppila:Pharmatest Services Ltd.: Employment. Rissanen:Pharmatest Services Ltd.: Equity Ownership. Luostarinen:Pharmatest Services Ltd.: Employment. Fagerlund:Pharmatest Services Ltd.: Employment, Equity Ownership. Sjöholm:Aurexel Life Sciences Ltd.: Employment. Alhoniemi:Avoltus Oy: Employment. Kakonen:Aurexel Life Sciences Ltd.: Employment, Equity Ownership. Siemeister:Bayer AG: Employment, Equity Ownership, Patents & Royalties. Mumberg:Bayer AG: Employment, Equity Ownership, Patents & Royalties. Halleen:Pharmatest Services Ltd.: Employment, Equity Ownership. Ziegelbauer:Bayer AG: Employment, Equity Ownership, Patents & Royalties. Scholz:Bayer AG: Employment, Equity Ownership, Patents & Royalties.
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