Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR)=0.8, 95% confidence interval (CI)=0.5–1.1) nor for latent antibodies (RR=0.6, 95% CI=0.1–2.7). Similar risks were seen when analysis was restricted to case–control sets with at least 2 years lag before diagnosis (RR=0.8, 95% CI=0.5–1.2 and RR=0.9, 95% CI=0.1–4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM

Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Publisher Copyright: © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.Peer reviewe

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2–8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA

Increasing prevalence and high incidence of celiac disease in elderly people: A population-based study

<p>Abstract</p> <p>Background</p> <p>Celiac disease may emerge at any age, but little is known of its appearance in elderly people. We evaluated the prevalence of the condition in individuals over 55 years of age, and determined the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s).</p> <p>Methods</p> <p>The study based on prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002. A second screening in the same population was carried out in 2005, comprising now 2216 individuals. Positive tissue transglutaminase antibodies were confirmed with small bowel biopsy.</p> <p>Results</p> <p>Within three years the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. Five new cases were found among patients previously seronegative; two had minor abdominal symptoms and three were asymptomatic. The incidence of celiac disease in 2002–2005 was 0.23%, giving an annual incidence of 0.08% in this population.</p> <p>Conclusion</p> <p>The prevalence of celiac disease was high in elderly people, but the symptoms were subtle. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may develop even in the elderly. Increased alertness to the disorder is therefore warranted.</p

Mikrobilääkeresistenssi ja -jäämät nautatilalla - vaikutukset ympäristöön ja terveyteen (NAMI)

Tässä Ruokaviraston (ennen Elintarviketurvallisuusvirasto Evira), Luken ja SYKEn yhteisprojektissa tutkittiin mikrobilääkejäämien ja resistenttien suolistobakteerien kulkeutumista lääkityistä lypsylehmistä navettaympäristön kautta lantavarastoihin. Lisäksi arvioitiin niiden leviämistä lannan peltolevitysten välityksellä luonnon eliöihin sekä elintarviketuotantoketjussa. Projektissa tutkittiin myös anaerobisen mesofiilisen mädätyksen vaikutuksia lannassa oleviin mikrobilääkejäämiin ja resistentteihin suolistobakteereihin sekä toisaalta lannan mikrobilääkejäämien vaikutusta mädädysprosessin toimintaan. Lisäksi arvioitiin erilaisten lannan prosessointitapojen elinkaarisia ympäristövaikutuksia sekä vaikutuksia mikrobilääkejäämiin ja -resistenssiin. Resistentit ja moniresistentit suolistobakteerit kulkeutuivat lypsykarjatilalla lantavarastoihin, mutta ne eivät rikastuneet lantaketjussa. Lypsykarjan lietelannasta mitattiin hyvin pieniä pitoisuuksia mikrobilääkkeitä. Lääkittyjen eläinten sonnasta ja virtsasta taas mitattiin hoidon aikana hyvin korkeita pitoisuuksia mikrobilääkejäämiä, jolloin niistä muodostuvissa (kuivissa) lannoissa voi olla korkeita paikallisia pitoisuuksia mikrobilääkkeitä. Suomessa myös mikrobilääkkeillä lääkittyjen eläinten lannat levitetään pääosin käsittelemättöminä kasvinravinteiksi pelloille, jolloin lannan mukana voi levitä mikrobilääkejäämiä ja resistenttejä suolistobakteereita. Luonnon eliöt voivat altistua lannassa oleville mikrobilääkkeille ja resistenteille suolistobakteereille myös Suomen olosuhteissa. Lääkittyjen eläinten lantojen lannoitekäyttöä käsittelemättömänä tulisi arvioida kriittisesti. Mesofiilinen anaerobinen mädätys voi vähentää mikrobilääkejäämiä lannasta, mutta ei välttämättä hajota niitä. Se vähentää elävien suolistobakteerien määrää lannassa, mutta merkittävää vaikutusta resistenttien E. coli -bakteerien osuuteen ei havaittu. Erilaiset lannankäsittelytavat voivat kuitenkin soveltua – ravinteiden kierrätyksen ja energiantuoton lisäksi – mikrobilääkejäämien ja resistenssin torjumiseen, ja niitä tulisikin tässä tarkoituksessa tutkia tarkemmin Suomessa.I detta samprojekt mellan Livsmedelsverket (före detta Livsmedelssäkerhetsverket Evira), Luke och SYKE undersöktes spridningen av resthalter av antimikrobiella läkemedel och resistenta tarmbakterier från behandlade mjölkkor till gödsellager via ladugårdsmiljön. Därtill uppskattades spridningen till organismer i naturen via gödselspridning på åkrar samt i livsmedelskedjan. I projektet undersöktes även effekten av anaerob mesofil rötning på resthalter av antimikrobiella medel i gödsel och resistenta tarmbakterier samt även effekten av resthalter av antimikrobiella medel på rötningsprocessen. Dessutom analyserades livscykeln för miljöpåverkan av de olika gödselbearbetningsmetoderna samt effekterna på resthalter av antimikrobiella medel och resistens. Resistenta och multiresistenta tarmbakterier spreds på mjölkgården till gödsellagren, men anrikades inte i gödselkedjan. Mycket små halter av antimikrobiella medel uppmättes i mjölkkornas flytgödsel. Men mycket höga resthalter av antimikrobiella medel uppmättes i gödsel och urin medan djuren behandlades, och då kan det finnas höga lokala halter av antimikrobiella medel i deras (torr)gödsel. I Finland sprids gödsel även av antibiotikabehandlade djur till största delen obehandlad som växtnäring på åkrar, och då kan resthalter av antimikrobiella medel och resistenta tarmbakterier spridas med gödseln. Organismer i naturen kan utsättas för antimikrobiella medel i gödsel och resistenta tarmbakterier även i finländska förhållanden. Användningen av obehandlad gödsel från medicinerade djur borde utvärderas kritiskt. Mesofil anaerob rötning kan minska på mängden resthalter av antimikrobiella medel i gödseln, men bryter inte nödvändigtvis ned dem. Den minskar på mängden levande tarmbakterier i gödseln, men ingen betydande effekt på andelen resistenta E.coli-bakterier påvisades. Olika sätt att behandla gödsel kan ändå, utöver återvinning av näringsämnen och energiproduktion, lämpa sig för bekämpning av antimikrobiella resthalter och resistens, och de borde undersökas mera detaljerat i Finland i det syftet.This study was conducted by Finnish Food Authority (formerly Finnish Food Safety Authority Evira), Natural Resources Institute Finland Luke and Finnish Environment Institute SYKE in 2015–2018. The aims of the study were to examine how antimicrobial residues and antimicrobial-resistant E. coli bacteria spread via the manure chain from the dairy cows treated with antimicrobials to the farm environment and manure storages. Furthermore, the dissemination routes to the surrounding environment, ecosystems and back to the food chain in Finnish conditions were profiled. The effect of mesophilic anaerobic digestion process on the level of antimicrobial residues and antimicrobial-resistant E. coli was examined and, conversely, the effect of antimicrobial residues on the process as well. Finally, the life-cycle of different manure handling and processing methods, and their potential effects on nutrient recycling, energy production, antimicrobial residues and resistant bacteria were evaluated. Resistant and multi-resistant E. coli spread to the manure storages, although enrichment in their proportion over the manure chain was not detected. Only minor concentrations of antimicrobial residues were measured from the liquid manure. Instead, very high concentrations of antimicrobial residues were measured from the faeces, urine and milk of dairy cows medicated with antimicrobials, which may lead to high local concentrations in (dry) manures composed of them. In Finland, there is no withdrawal period for manure of medicated animals to be used as a fertilizer. Therefore, manures may contain antimicrobial residues, as well as resistant bacteria, which disseminate to the environment when applied to the fields. Animals and plants may be exposed to antimicrobial residues and resistant bacteria in agricultural and natural ecosystems in Finnish conditions as well. Therefore, fertilizer usage of faeces, urine and milk excreted by animals treated with antimicrobials should be subjected to critical assessment. Treating the manure with mesophilic anaerobic digestion may reduce the concentration of antimicrobial residues but does not necessarily destroy them. Furthermore, the process reduced the number of total E. coli bacteria, although it did not have an effect on the proportion of resistant E. coli. Along with energy production and nutrient recycling, different manure handling and processing methods may, however, be suitable for destroying and reducing antimicrobial residues and resistant bacteria from manure, and substantially reduce the emission of antimicrobial residues and resistant bacteria to the environment, as well as to the food chain. The aspect of tackling the spread of antimicrobial resistance is to be considered when manure processing methods are developed in Finland

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case–cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1–8.2) and HPV 18 (OR=4.4; 95%CI=1.1–17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer

MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), numbers 2008/03232-1 (to L.L. Villa) and 2012/09746-2 (to M.G. Discacciati and S.S. Maria-Engler) and National Counsel of Technological and Scientific Development pharmaceutical innovation (CNPQ-INCT-if; to S.S. Maria-Engler)

Oral contraceptive use before first birth and risk of breast cancer: a case control study

BACKGROUND: The aim of this study was first, to investigate whether women starting oral contraceptive (OC) use at a young age and before first birth have an increased risk for breast cancer and second, to report difficulties encountered in studying long-term health impacts of medical technologies. METHODS: Breast cancers occurring up until 1997 among 37153 Helsinki students born between 1946 and 1960 were identified by record linkage from the Finnish Cancer Registry; for each cancer case, five age-matched random controls were picked from the same student population. Those who had used the Helsinki Student Health Service (HSHS) at least three times (150 cases and 316 controls) form the final study subjects. Data on OC use and background characteristics were collected from patient records, and data on live births were derived from the population register. Odds ratios (OR) were adjusted for number of births, smoking and sports activity. RESULTS: Compared to the few non-users, OC users had a higher risk of breast cancer: the adjusted OR was 2.1 (95% confidence interval 1.1–4.2). Among OC users, no statistically significant differences in risk of breast cancer were found in regard to starting age or first birth, but small numbers made confidence intervals wide. Even though we had chosen students to be our study group, the population turned out to be unsuitable to answer our research question: most women had started their OC use old (at the age of 20 or later) and there were very few unexposed (almost all had used OC and before their first birth). CONCLUSIONS: Because adoption of the modern pattern of OC use was not common among students, it is unlikely that the impact of early and extended OC use can be studied before 2010, when women born in the 1960s are 40 to 50 years old

Policy drivers of international entrepreneurship in Europe

The diversity of countries and cultures in Europe necessitates an international outlook for most businesses. This paper examines the internationalisation of business in Europe through a literature review on international entrepreneurship theory. The role of the individual business owner and of business and interorganisational activity in facilitating the internationalisation of businesses in Europe is discussed by utilising the theoretical framework of international entrepreneurship and by putting forward three main propositions. The main aim and intent of this paper is to understand how the policies of individual governments and institutions such as the European Union help businesses in Europe to internationalise, with particular emphasis on businesses in the Baltic region. The paper discusses policy implications and suggestions for future research, which highlight the importance for firms in Europe of focussing on international markets.<br /