Pharmaceutical emissions on the example of the Baltic Sea catchment: comparing measurements with multi-tier predictive models.

Currently, there is uncertainty about emissions of pharmaceuticals into larger closed ecosystems that are at risk such as the Baltic Sea. There is an increasing need for selecting the right strategies on advanced wastewater treatment. This study analysed 35 pharmaceuticals and iodinated X-ray contrast media in effluents from 82 Wastewater Treatment Plants (WWTPs) across Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Poland and Sweden.

Elimination of HPV-associated oropharyngeal cancers in Nordic countries.

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50-69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980's. The recent implementation of school-based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries.

Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.

We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each.

Alkane and wax ester production from lignin-related aromatic compounds.

Lignin has potential as a sustainable feedstock for microbial production of industrially relevant molecules. However, the required lignin depolymerization yields a heterogenic mixture of aromatic monomers that are challenging substrates for the microorganisms commonly used in the industry. Here, we investigated the properties of lignin-related aromatic compounds (LRAs), namely coumarate, ferulate, and caffeate, in the synthesis of biomass and products in an LRA-utilizing bacterial host Acinetobacter baylyi ADP1.

Synthetic metabolic pathway for the production of 1-alkenes from lignin-derived molecules.

Background: Integration of synthetic metabolic pathways to catabolically diverse chassis provides new opportunities for sustainable production. One attractive scenario is the use of abundant waste material to produce a readily collectable product, which can reduce the production costs. Towards that end, we established a cellular platform for the production of semivolatile medium-chain α-olefins from lignin-derived molecules: we constructed 1-undecene synthesis pathway in Acinetobacter baylyi ADP1 using ferulate, a lignin-derived model compound, as the sole carbon source for both cell growth and product synthesis.

Production of alkanes from CO by engineered bacteria.

Background: Microbial biosynthesis of alkanes is considered a promising method for the sustainable production of drop-in fuels and chemicals. Carbon dioxide would be an ideal carbon source for these production systems, but efficient production of long carbon chains from CO is difficult to achieve in a single organism. A potential solution is to employ acetogenic bacteria for the reduction of CO to acetate, and engineer a second organism to convert the acetate into long-chain hydrocarbons.

Metabolic pairing of aerobic and anaerobic production in a one-pot batch cultivation.

Background: The versatility of microbial metabolic pathways enables their utilization in vast number of applications. However, the electron and carbon recovery rates, essentially constrained by limitations of cell energetics, are often too low in terms of process feasibility. Cocultivation of divergent microbial species in a single process broadens the metabolic landscape, and thus, the possibilities for more complete carbon and energy utilization.

Improved fatty aldehyde and wax ester production by overexpression of fatty acyl-CoA reductases.

Background: Fatty aldehydes are industrially relevant compounds, which also represent a common metabolic intermediate in the microbial synthesis of various oleochemicals, including alkanes, fatty alcohols and wax esters. The key enzymes in biological fatty aldehyde production are the fatty acyl-CoA/ACP reductases (FARs) which reduce the activated acyl molecules to fatty aldehydes. Due to the disparity of FARs, identification and in vivo characterization of reductases with different properties are needed for the construction of tailored synthetic pathways for the production of various compounds.

Human Papillomavirus (HPV) Prevalence in Male Adolescents 4 Years After HPV-16/18 Vaccination.

We assessed human papillomavirus (HPV) prevalence among HPV-16/18-vaccinated and unvaccinated Finnish male adolescents participating in chlamydia screening 4 years after vaccination with AS04-adjuvanted HPV-16/18 vaccine in 2007-2009. Previously vaccinated (n = 395) or unvaccinated (n = 149) male adolescents were enrolled in 12 municipalities. First-void urine samples were tested for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 66, and 68, and prevalence rates for HPV-16/18, and HPV-11/16/18/31/33/45 were reduced profoundly (0% vs 2.

Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma.

Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses.

Proprotein convertase expression in the fat body is essential for a normal antimicrobial peptide response and bacterial host defense.

Invading pathogens provoke robust innate immune responses in Dipteran insects, such as In a systemic bacterial infection, a humoral response is induced in the fat body. Gram-positive bacteria trigger the Toll signaling pathway, whereas gram-negative bacterial infections are signaled the immune deficiency (IMD) pathway. We show here that the RNA interference-mediated silencing of -a member of the proprotein convertase enzyme family-specifically in the fat body, results in a reduction in the expression of antimicrobial peptides.

Production of long chain alkyl esters from carbon dioxide and electricity by a two-stage bacterial process.

Microbial electrosynthesis (MES) is a promising technology for the reduction of carbon dioxide into value-added multicarbon molecules. In order to broaden the product profile of MES processes, we developed a two-stage process for microbial conversion of carbon dioxide and electricity into long chain alkyl esters. In the first stage, the carbon dioxide is reduced to organic compounds, mainly acetate, in a MES process by Sporomusa ovata.

Twin-layer biosensor for real-time monitoring of alkane metabolism.

Intracellular metabolic sensors can be used for efficient screening and optimization of microbial cell factories. In particular, the sensors are useful in acquiring information about pathway dynamics and bottlenecks in a straightforward manner. Here, we developed a twin-layer biosensor that functions simultaneously at two levels: through transcription factor mediated sensing and enzyme-metabolite interaction, providing insights into the dynamics of alkane metabolism.

The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables.

Constant pattern of relapse in primary central nervous lymphoma patients treated with high-dose methotrexate combinations. A Finnish retrospective study.

Background: Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome is poor.

Material And Methods: We performed a hospital-based retrospective analysis to evaluate the long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL patients.

[Childhood and adolescent cancer was cured--how to support health in adulthood?].

The number of long-term survivors after cancer therapy in childhood and young adulthood is increasing. Accordingly, life-long follow-up of significant health problems related to the given cancer therapy is needed as only one third of the survivors will remain free of any physical or psychosocial late effects. At present, national activity is needed to establish a uniform follow-up clinic service to support education, diagnostics, therapy and rehabilitation of these long-term adverse effects after cancer therapy at young age.

Diffuse large B cell lymphoma derived from nodular lymphocyte predominant Hodgkin lymphoma presents with variable histopathology.

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL.

Three randomised phase I/IIa trials of 5% cis-urocanic acid emulsion cream in healthy adult subjects and in patients with atopic dermatitis.

New treatment modalities are needed in atopic dermatitis. We evaluated the pharmacokinetics, safety, tolerability, and efficacy of topical cis-urocanic acid (cis-UCA) cream in randomised vehicle-controlled double-blinded clinical trials. The subjects received 5% cis-UCA emulsion cream and control vehicle on volar forearms after right-left randomisation.

Neointimal coverage and vasodilator response to titanium-nitride-oxide-coated bioactive stents and everolimus-eluting stents in patients with acute coronary syndrome: insights from the BASE-ACS trial.

Incomplete stent endothelialization is associated with late and very late stent thrombosis. In a post hoc analysis of the BASE-ACS trial, we sought to assess neointimal coverage and coronary flow reserve (CFR) 9 months after implantation of titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). In the BASE-ACS trial, 827 patients with ACS were randomized to receive either BAS or EES.

Bioremediation trial on aged PCB-polluted soils--a bench study in Iceland.

Polychlorinated biphenyls (PCBs) pose a threat to the environment due to their high adsorption capacity to soil organic matter, stability and low reactivity, low water solubility, toxicity and ability to bioaccumulate. With Icelandic soils, research on contamination issues has been very limited and no data has been reported either on PCB degradation potential or rate. The goals of this research were to assess the bioavailability of aged PCBs in the soils of the old North Atlantic Treaty Organization facility in Keflavík, Iceland and to find the best biostimulation method to decrease the pollution.

Effects of ospemifene on drug metabolism mediated by cytochrome P450 enzymes in humans in vitro and in vivo.

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism.

Effects of cytochrome P450 inhibitors and inducers on the metabolism and pharmacokinetics of ospemifene.

Purpose: The objectives were to determine the cytochrome P450 (CYP) enzymes involved in the metabolism of ospemifene and its main hydroxylated metabolites and to examine the effects of CYP inhibitors and inducers on ospemifene pharmacokinetics.

Methods: In vitro metabolism studies were conducted using human liver microsomes; CYP-selective inhibitors and CYP-specific substrates were used to determine the roles of nine CYP isoforms in ospemifene metabolism. Two Phase 1 clinical trials were conducted in healthy postmenopausal women; crossover designs examined the effects of pretreatment with the CYP modulators rifampicin, ketoconazole, fluconazole and omeprazole on ospemifene pharmacokinetics.

Cold-related cardiorespiratory symptoms among subjects with and without hypertension: the National FINRISK Study 2002.

Background: Exposure to cold weather increases blood pressure (BP) and may aggravate the symptoms and influence the prognosis of subjects with a diagnosis of hypertension. We tested the hypothesis that subjects with hypertension alone or in combination with another cardiovascular disease (CVD) experience cold-related cardiorespiratory symptoms more commonly than persons without hypertension. This information is relevant for proper treatment and could serve as an indicator for predicting wintertime morbidity and mortality.