Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.

Transition of young people with chronic conditions: a cross-sectional study of patient perceptions before and after transfer from pediatric to adult health care.

UNLABELLED: The aim of this study was to compare perceived barriers to and the most preferred age for successful transition to adult health care between young people with chronic disorders who had not yet transferred from pediatric to adult health care (pre-transfer) and those who had already transferred (post-transfer). In a cross-sectional study, we compared 283 pre-transfer with 89 post-transfer young people, using a 28-item questionnaire that focused on perceived barriers to transition and beliefs about the most preferred age to transfer. Feeling at ease with the pediatrician was the most important barrier to successful transition in both groups, but was rated significantly higher in the pre-transfer compared to the post-transfer group (OR = 2.03, 95 %CI 1.12-3.71). Anxiety and lack of information were the next most important barriers, rated equally highly by the two groups (OR = 0.67, 95 %CI 0.35-1.28 and OR = 0.71, 95 %CI 0.36-1.38, respectively). More than 80 % of the respondents in both groups reported that 16-19 years was the most preferred age to transfer; more than half of all the respondents reported 18-19 years and older as the most preferred age. CONCLUSION: Better transition planning through the provision of regular and more detailed information about adult health-care providers and the transition process could reduce anxiety and contribute to a more positive attitude to overcome perceived barriers to transition from young people's perspective. Young people's preferences about transferring to adult health care provide a challenge to those children's hospitals that transfer to adult health care at a younger age.

Social Support, Social and Temporal Comparisons Protect Well-Being and Health between 45 and 70 Years Old in Four Urban Communities

This study examined the impact of social support and of temporal and social comparisons on well-being and selfreported health in four capital cities: Paris, Berlin, Moscow and Beijing. Based on the lifespan control theory, an integrative model investigating the influence of these coping strategies, especially on the psychological regulation of health losses, was tested on 1141 respondents aged 45 to 70 years by using structural equation modelling with multigroup comparisons. Results indicated a good fit of the model to participants' responses. In all contexts, physical weaknesses favoured the use of social and temporal comparison strategies rather than social support. Moreover, across the cities, coping strategies were oriented more toward protecting self-evaluation of health than toward enhancement of well-being. Social comparison decreased the impact of physical weaknesses on health evaluation and on well-being in the four cities, but to a lesser extent in China. Results are discussed regarding the normative cross-cultural aspects that intervene during ageing in the four urban contexts.

Tackling Societal Challenges Related to Ageing and Transport Transition: An Introduction to Philosophical Principles of Causation Adapted to the Biopsychosocial Model

In geriatrics, driving cessation is addressed within the biopsychosocial model. This has broadened the scope of practitioners, not only in terms of assessing fitness to drive, but also by helping to maintain social engagements and provide support for transport transition. Causes can be addressed at different levels by adapting medication, improving physical health, modifying behaviour, adapting lifestyle, or bringing changes to the environment. This transdisciplinary approach requires an understanding of how different disciplines are linked to each other. This article reviews the philosophical principles of causality between fields and provides a framework for understanding causality within the biopsychosocial model. Understanding interlevel constraints should help practitioners overcome their differences, and favor transversal approaches to driving cessation.

Development of a population-based cost-effectiveness model of chronic graft versus host disease in Spain

Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. METHODS: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for ( 517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was 29,646 per life-year gained and 24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. CONCLUSION: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt.

Patients' Needs for Care in Public Mental Health: Unity and Diversity of Self-Assessed Needs for Care.

PURPOSE: Needs assessment is recognized to be a key element of mental health care. Patients tend to present heterogeneous profiles of needs. However, there is no consensus in previous research about how patients' needs are organized. This study investigates both general and specific dimensions of patients' needs for care. METHODS: Patients' needs were assessed with ELADEB, an 18-domain self-report scale. The use of a self-assessment scale represents a unique way of obtaining patients' perceptions. A patient-centered psychiatric practice facilitates empowerment as it is based on the patients' personal motivations, needs, and wants. Four seventy-one patients' profiles were analyzed through exploratory factor analysis. RESULTS: A four-factor bifactor model, including one general factor and three specific factors of needs, was most adequate. Specific factors were (a) "finances" and "administrative tasks"; (b) "transports," "public places," "self-care," "housework," and "food"; and (c) "family," "children," "intimate relationships," and "friendship." CONCLUSION: As revealed by the general factor, patients expressing urgent needs in some domains are also more susceptible to report urgent needs in several other domains. This general factor relates to high versus low utilizers of public mental healthcare. Patients also present specific needs in life domains, which are organized in three dimensions: management, functional disabilities, and familial and interpersonal relationships. These dimensions relate to the different types of existing social support described in the literature.

Older consumers adopting information and communication technology: Evaluating opportunities for health care applications

The purpose of this dissertation is to analyse older consumers' adoption of information and communication technology innovations, assess the effect of aging related characteristic, and evaluate older consumers' willingness to apply these technologies in health care services. This topic is considered important, because the population in Finland (as in other welfare states) is aging and thus offers a possibility for marketers, but on the other hand threatens society with increasing costs for healthcare. Innovation adoption has been under research from several aspects in both organizational and consumer research. In the consumer behaviour, several theories have been developed to predict consumer responses to innovation. The present dissertation carefully reviews previous research and takes a closer look at the theory of planned behaviour, technology acceptance model and diffusion of innovations perspective. It is here suggested that there is a possibility that these theories can be combined and complemented to predict the adoption of ICT innovations among aging consumers, taking the aging related personal characteristics into account. In fact, there are very few studies that have concentrated on aging consumers in the innovation research, and thus there was a clear indent for the present research. ICT in the health care context has been studied mainly from the organizational point of view. If the technology is thus applied for the communication between the individual end-user and service provider, the end-user cannot be shrugged off. The present dissertation uses empirical evidence from a survey targeted to 55-79 year old people from one city in Southern-Carelia. The empirical analysis of the research model was mainly based on structural equation modelling that has been found very useful on estimating causal relationships. The tested models were targeted to predict the adoption stage of personal computers and mobile phones, and the adoption intention of future health services that apply these devices for communication. The present dissertation succeeded in modelling the adoption behaviour of mobile phones and PCs as well as adoption intentions of future services. Perceived health status and three components behind it (depression, functional ability, and cognitive ability) were found to influence perception of technology anxiety. Better health leads to less anxiety. The effect of age was assessed as a control variable, in order to evaluate its effect compared to health characteristics. Age influenced technology perceptions, but to lesser extent compared to health. The analyses suggest that the major determinant for current technology adoption is perceived behavioural control, and additionally technology anxiety that indirectly inhibit adoption through perceived control. When focusing on future service intentions, the key issue is perceived usefulness that needs to be highlighted when new services are launched. Besides usefulness, the perception of online service reliability is important and affects the intentions indirectly. To conclude older consumers' adoption behaviour is influenced by health status and age, but also by the perceptions of anxiety and behavioural control. On the other hand, launching new types of health services for aging consumers is possible after the service is perceived reliable and useful.

A qualitative analysis of immigrant population health practices in the Girona Healthcare Region

The research we present here forms part of a two-phase project - one quantitative and the other qualitative - assessing the use of primary health care services. This paper presents the qualitative phase of said research, which is aimed at ascertaining the needs, beliefs, barriers to access and health practices of the immigrant population in comparison with the native population, as well as the perceptions of healthcare professionals. Moroccan and sub-Saharan were the immigrants to who the qualitative phase was specifically addressed. The aims of this paper are as follows: to analyse any possible implications of family organisation in the health practices of the immigrant population; to ascertain social practices relating to illness; to understand the significances of sexual and reproductive health practices; and to ascertain the ideas and perceptions of immigrants, local people and professionals regarding health and the health system. Methods: qualitative research based on discursive analysis. Data gathering techniques consisted of discussion groups with health system users and semi-structured individual interviews with healthcare professionals. The sample was taken from the Basic Healthcare Areas of Salt and Banyoles (belonging to the Girona Healthcare Region), the discussion groups being comprised of (a) 6 immigrant Moroccan women, (b) 7 immigrant sub-Saharan African women and (c) 6 immigrant and native population men (2 native men, 2 Moroccan men and 2 sub-Saharan men); and the semi-structured interviews being conducted with the following healthcare professionals: (a) 3 gynaecologists, (b) 3 nurses and 1 administrative staff. Results: use of the healthcare system is linked to the perception of not being well, knowledge of the healthcare system, length of time resident in Spain and interiorization of traditional Western medicine as a cure mechanism. The divergences found among the groups of immigrants, local people and healthcare professionals with regard to healthcare education, use of the healthcare service, sexual and reproductive healthcare and reticence with regard to being attended by healthcare personnel of the opposite sex demonstrate a need to work with the immigrant population as a heterogeneous group. Conclusions: the results we have obtained support the idea that feeling unwell is a psycho-social process, as it takes place within a specific socio-cultural situation and spans a range of beliefs, perceptions and ideas regarding symptomology and how to treat it

Machine Learning and Clinical Text. Supporting Health Information Flow

Fluent health information flow is critical for clinical decision-making. However, a considerable part of this information is free-form text and inabilities to utilize it create risks to patient safety and cost-­effective hospital administration. Methods for automated processing of clinical text are emerging. The aim in this doctoral dissertation is to study machine learning and clinical text in order to support health information flow.First, by analyzing the content of authentic patient records, the aim is to specify clinical needs in order to guide the development of machine learning applications.The contributions are a model of the ideal information flow,a model of the problems and challenges in reality, and a road map for the technology development. Second, by developing applications for practical cases,the aim is to concretize ways to support health information flow. Altogether five machine learning applications for three practical cases are described: The first two applications are binary classification and regression related to the practical case of topic labeling and relevance ranking.The third and fourth application are supervised and unsupervised multi-class classification for the practical case of topic segmentation and labeling.These four applications are tested with Finnish intensive care patient records.The fifth application is multi-label classification for the practical task of diagnosis coding. It is tested with English radiology reports.The performance of all these applications is promising. Third, the aim is to study how the quality of machine learning applications can be reliably evaluated.The associations between performance evaluation measures and methods are addressed,and a new hold-out method is introduced.This method contributes not only to processing time but also to the evaluation diversity and quality. The main conclusion is that developing machine learning applications for text requires interdisciplinary, international collaboration. Practical cases are very different, and hence the development must begin from genuine user needs and domain expertise. The technological expertise must cover linguistics,machine learning, and information systems. Finally, the methods must be evaluated both statistically and through authentic user-feedback.

Venäläistä rulettia – Nuorten perhesuunnittelun esteet ja tarpeet Pietarissa ja Riiassa

Latviassa ja Venäjällä heikko demografinen tilanne on lisännyt keskustelua seksuaali- ja kansalaisoikeuksista sekä valtion merkityksestä niiden toteuttamisessa. Väestöpolitiikassa näkyy yhteiskunnallinen tilanne sekä sen kyky ja mahdollisuudet huomioida nuorten perhesuunnitteluun liittyviä tarpeita. Huomion kohteena on myös palvelujärjestelmä ja siinä toteutuva yksilöllinen taso. Tutkin perhesuunnittelua kokonaisvaltaisesti, mikä ilmenee erilaisten polkuriippuvuuksien tarkasteluina. Mielenkiintoiseksi kohteen tekee entisten sosialististen valtioiden erityislaatuisen murroksen läpikäyminen. Perhesuunnittelu on osa seksuaali- ja ihmisoikeuksia. Siihen kuuluu seksuaaliterveydestä tiedottaminen ja ohjaus sekä siihen liittyvät toimenpiteet. Perhesuunnittelu sisältää niin sosiaaliset, kasvatukselliset kuin lääketieteellisetkin näkökulmat. Siihen liitetään myös moraalisia ja taloudellisia näkemyksiä, sekä politiikkaa ja henkilökohtaisuutta. Tutkimustehtäväni on nuorten perhesuunnittelun esteet ja tarpeet Riiassa ja Pietarissa. Sovellan metodologisena lähestymistapana sosiaalihistoriallista ja etnografista tutkimusotetta, jolloin perinteen vaikutusten, kulttuuristen rakenteiden ja yksilöllisten toimintatapojen ymmärtäminen mahdollistuu. Aineisto koostuu viranomaishaastatteluista sosialismin kaudella toteutuneesta sekä nykyisestä perhesuunnittelusta ja nuorten haastatteluista Pietarissa ja Riiassa. Perehdyn myös lisääntymisterveyteen liittyviin sanomalehtiartikkeleihin sekä Latviassa että Venäjällä. Lisäksi havainnoin seksuaalineuvontatilanteita Pietarissa. Sekä sosialismin aikana että nykyään painottuvat väestönkasvun odotukset, joita tuetaan sukupuoli- ja moraalikasvatuksen avulla. Perhesuunnittelun esteiden analyysin tuloksissa on nähtävissä sosiaalisten olosuhteiden ja rakenteiden merkitys. Jälkisosialistisesta riskiyhteiskunnasta puuttuvat yhteiskuntaan integroitumisen mahdollistavat instituutiot. Tämä ilmenee yhteiskunnallisena vastuuttomuutena. Universaalit palvelut ovat suurelta osin peräisin sosialismin ajalta. Kaupalliset yritykset tekevät lähinnä teknisiä, yksittäisiä ehkäisyvälineisiin liittyviä interventioita nuorten elämään. Teini-ikäiset jätetään oman harkintansa varaan. Latviassa perhesuunnitteluun liittyvä ennalta ehkäisevä toiminta on huomioitu uudessa lisääntymisterveyslaissa, mutta sen heikko toteutus tuo sen lähelle neuvostoaikaista kulttuurikonventiota, jossa määrällisillä suoritteilla ja sekundaaripreventiolla on arvoa. Venäjällä voimavarat kohdentuvat jälkihuollon palveluihin. Foucaultin valta-analyysi kertoo strategiasta, jossa ihminen sisäistää vallankäytön osaksi omaa ajatteluaan ja toimintaansa. Tässä näkökulmassa yksilöllinen, yhteiskunnallinen ja historiallinen ulottuvuus limittyvät toisiinsa. Vallan muodot ovat yhteiskunnan rakenteissa. Väestöpolitiikan avulla tuotetaan tietoa ja muovataan hallitsemisen kohteita. Osa haastatelluista nuorista omaksui yhteiskunnan passiivisuuden osaksi omaa toimintaansa. He eivät tiedostaneet palvelujärjestelmän puutteita eivätkä kyseenalaistaneet sen oikeutusta. Myös lehtiartikkelit ja viranomaishaastattelut tukivat osittain seksuaalikasvatuksen sivuuttamista. Silloin hyväksyttävänä totuutena pidettiin väestöpolitiikkaa, jossa on annettu tilaa populistisille suuntauksille. Sekä Latviassa että Venäjällä ilmaistiin tavoitteita väestön kasvusta. Kansainvälisten seksuaalioikeuksien maihinnousu ei ole poistanut ääri uskonnollisten ja osittain kansalaisjärjestöjen puitteissa tapahtuvaa perhesuunnittelun vastustusta. Näissä suuntauksissa vaikutetaan ihmisten moraaliin ja vastustetaan yhteiskunnan interventioita kieltämällä seksuaalikasvatus. Sosialismin aikana sosiaali- ja terveydenhuoltoa toteutettiin totalitaristisessa, suljetussa yhteiskunnassa tiukasti rajatuilla voimavaroilla. Tuolta ajalta peräisin oleva viranomaisten yleinen medikalisoitunut ja tekninen lähestymistapa estää osittain nuoren valtaistumista. Vieläkin heikko tiedottaminen ja puutteellinen koulutus vaikuttavat ammattilaisten keskuudessa. Yksi haitallisista perhesuunnitteluun kuuluvista uskomuksista oli hormonaalisen ehkäisyn aiheuttamat ongelmat. Lisäksi pelättiin heikkotasoisesti tehtyjen aborttien aiheuttavan hedelmättömyyttä. Uskomukset ovat eläneet vieläkin, kun osa asiantuntijoista kannusti ensimmäisen raskauden päättymistä synnytykseen. Näillä käsityksillä on ollut taipumus siirtyä sukupolvelta toiselle myös kansalaisten keskuudessa. Sukuyhteisöjen ja verkostojen oleellinen merkitys teini-ikäisen arjessa ja selviytymisessä painotti perinteistä sosialisaatiota. Uskomusten lisäksi nuorten heikko taloudellinen tilanne on ohjannut heitä ehkäisyssä luonnonmenetelmien käyttöön. Neuvostoaikainen seksuaalikielteisyyden perinne on vaikuttanut myös sukupolvien kyvyttömyyteen keskustella aiheesta. Yleisen ennaltaehkäisevän neuvonnan puuttuminen on suunnannut suurta osaa nuoria mallioppimiseen, jossa esimerkit ovat nousseet satunnaisista löydöistä. Toisaalta työntekijöiden neuvokkuus ja aloitteellisuus erilaisissa ohjaamistilanteissa, toimintatavoissa ja instituutioiden perustamisissa kuvaavat eettistä vastuunottoa ja paneutumista nuorten perhesuunnittelun toteutumiseen sekä sen mahdollisuuksiin. Perhesuunnitteluun liittyvän tiedonsaannin parantamiseksi viranomaiset ovat aloittaneet nuorten vertaisryhmiä. Lisäksi yhtenä uutena virallisena lähestymistapana oli neuvostoaikana kielletty psykoterapeuttisen suuntauksen avoin käyttöönotto. Myös nuorille suunnattuja palveluja niin lainsäädännön kuin instituutioiden tasolla on saatu aikaan. Nämä myönteiset tapaukset jäivät kuitenkin yksittäisiksi, osittain joidenkin työntekijöiden omakohtaisen sitoutumisen varaan toimiviksi. Tutkimuksessa nousee esiin yhteiskunnan vastuu erityisesti haavoittuvien ryhmien kohdalla. Nuoret ovat tiedoiltaan ja kokemuksiltaan heikossa asemassa. Sosiaalipoliittisesta näkökulmasta julkisilla ja ennaltaehkäisevillä palveluilla on keskeinen merkitys etenkin niiden kohdalla, jotka tarvitsevat runsaasti palveluja. Usein tähän ryhmään kuuluvat ovat passiivisia tiedon hakijoita. Tutkimus tuo esille perhesuunnittelun palvelujärjestelmään ja sen kohderyhmään kuuluvan moniulotteisuuden, jossa toisiinsa nivoutuvat kulttuuriset myytit, uskomukset, tabut, toimintatavat ja tietämys. Näiden polkujen avaaminen tässä tutkimuksessa edistää perhesuunnittelun esteiden tunnistamista ja niihin soveltuvien ratkaisukeinojen löytymistä.

Perceptions of health club exercise among middle-aged women

The goal of this Master’s Thesis is to investigate the typical perceptions of health club exercise among middle-aged women. This study is conducted for a Finnish health club Viva Wellness Club due to their interest to examine the perceived barriers of middle-aged women to exercise at their health club. In addition, the behavioral beliefs, normative beliefs, motivation and facilitating factors concerning health club exercise are studied. The social aspect of health clubs as social environments is taken into account. The study is conducted qualitatively with semi-structured interviews Eight customers from Viva Wellness Club are interviewed. The findings revealed that the consumers perceived health club exercise as important, effective, diverse and convenient. Despite the fact that some differences were found, the perceptions about exercise in general concurred with the contestants’ perceptions about health club exercise. The perceived barriers to health club exercise encompassed lack of time, tiredness, health restrictions, weather, family commitments and feelings of embarrassment about one’s appearance and condition.

Determinants of Bone Strength and Predictors of Hip Fracture among Finnish Adults. Results from the Health 2000 Survey and the Mini-Finland Health Survey

The objective of this thesis was to identify the determinants of bone strength and predictors of hip fracture in representative samples of Finnish adults. A secondary objective was to construct a simple multifactorial model for hip fracture prediction over a 10-year follow-up period. The study was based on the Health 2000 Survey conducted during 2000 to 2001 (men and women aged 30 years or over, n=6 035) and the Mini-Finland Health Survey conducted during 1978 to 1980 (women aged 45 years or over, n=2 039). Study subjects participated in health interviews and comprehensive health examination. In the Health 2000 Survey, bone strength was assessed by means of calcaneal quantitative ultrasound (QUS). The follow-up information about hip fractures was drawn from the National Hospital Discharge Register. In this study, age, weight, height, serum 25-hydroxyvitamin D (S-25(OH)D), physical activity, smoking and alcohol consumption as well as menopause and eventual HRT in women were found to be associated with calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS). Parity was associated with a decreased risk of hip fracture in postmenopausal women. Age, height, weight or waist circumference, quantitative ultrasound index (QUI), S-25(OH)D and fall-related factors, such as maximal walking speed, Parkinson’s disease, and the number of prescribed CNS active medication were significant independent predictors of hip fracture. At the population level, the incremental value of QUS appeared to be minor in hip fracture prediction when the fall-related risk factors were taken into account. A simple multifactorial model for hip fracture prediction presented in this study was based on readily available factors (age, gender, height, waist circumference, and fallrelated factors). Prospective studies are needed to test this model in patient-based study populations.

Animal model for age- and sex-related genotoxicity of diethylstilbestrol

Environmental xenoestrogens pose a significant health risk for all living organisms. There is growing evidence concerning the different susceptibility to xenoestrogens of developing and adult organisms, but little is known about their genotoxicity in pre-pubertal mammals. In the present study, we developed an animal model to test the sex- and age-specific genotoxicity of the synthetic estrogen diethylstilbestrol (DES) on the reticulocytes of 3-week-old pre-pubertal and 12-week-old adult BALB/CJ mice using the in vivo micronucleus (MN) assay. DES was administered intraperitoneally at doses of 0.05, 0.5, and 5 µg/kg for 3 days and animals were sampled 48, 72 and 96 h, and 2 weeks after exposure. Five animals were analyzed for each dose, sex, and age group. After the DES dose of 0.05 µg/kg, pre-pubertal mice showed a significant increase in MN frequency (P < 0.001), while adults continued to show reference values (5.3 vs 1.0 MN/1000 reticulocytes). At doses of 0.5 and 5 µg/kg, MN frequency significantly increased in both age groups. In pre-pubertal male animals, MN frequency remained above reference values for 2 weeks after exposure. Our animal model for pre-pubertal genotoxicity assessment using the in vivo MN assay proved to be sensitive enough to distinguish age and sex differences in genome damage caused by DES. This synthetic estrogen was found to be more genotoxic in pre-pubertal mice, males in particular. Our results are relevant for future investigations and the preparation of legislation for drugs and environmentally emitted agents, which should incorporate specific age and gender susceptibility.

Evaluation of a new mathematical model to describe Clostridium perfringens growth during the cooling of cooked ground beef

A mathematical model previously developed to study microbial growth in food products under an isothermal environment was adapted to a time-varying temperature regime. The resulting model was applied to study the growth of Clostridium perfringens in meat products. This micro-organism is of particular relevance to public health and economy due to the loss of productivity caused by it. Results showed a similar performance of the model used compared to the Baranyi model under an isothermal situation and a slightly better performance under a non-isothermal temperature profile.

Roles of keratins in intestinal health and disease

Intermediate filament keratins (K) play a pivotal role in protein targeting and epithelialcytoprotection from stress as evidenced by keratin mutations predisposing to human liver and skin diseases and possibly inflammatory bowel disease (IBD). The K8-null (K8-/-) mice exhibit colonic phenotype similar to IBD and marked spontaneous colitis, epithelial hyperproliferation, decreased apoptosis, mistargeting of proteins leading to defective ion transport and diarrhea. The K8-heterozygote (K8+/-) mouse colon appears normal but displays a defective sodium (Na+) and chloride (Cl-) transport similar to, but milder than K8-/-. Characterization of K8+/- colon revealed ~50% less keratins (K7, K8, K19, K20) compared to K8 wild type (K8+/+). A similar ~50% decrease was seen in K8+/- mRNA levels as compared to K8+/+, while the mRNA levels for the other keratins were unaltered. K8+/- keratins were arranged in a normal colonic crypt expression pattern, except K7 which was expressed at the top of crypts in contrast to K8+/+. The K8+/- colon showed mild hyperplasia but no signs of inflammation and no resistance to apoptosis. Experimental colitis induced by using different concentrations of dextran sulphate sodium (DSS) showed that K8+/- mice are slightly more sensitive to induced colitis and showed a delayed recovery compared to K8+/+. Hence, the K8+/- mouse with less keratins and without inflammation, provided a novel model to study direct molecular mechanisms of keratins in intestinal homeostasis and ion transport. Different candidate ion transporters for a possible role in altered ion transport seen in the K8-/- and K8+/- mouse colon were evaluated. Besides normal levels of CFTR, PAT-1 and NHE-3, DRA mRNA levels were decreased 3-4-fold and DRA protein nearly entirely lost in K8-/- caecum, distal and proximal colon compared to K8+/+. In K8+/- mice, DRA mRNA levels were unaltered while decreased DRA protein level and patchy distribution was detected particularly in the proximal colon and as compared to K8+/+. DRA was similarly decreased when K8 was knocked-down in Caco-2 cells, confirming that K8 levels modulate DRA levels in an inflammation-independent manner. The dramatic loss of DRA in colon and caecum of K8-/- mice was responsible for the chloride transport defect. The milder ion transport in K8+/- colon might be related to DRA suggesting a role for K8 in regulation of DRA expression and targeting. The current study demonstrates the importance of keratins in stress protection and cell signaling. Furthermore, we have also successfully developed a novel, simple, fast, cost effective, non-invasive in vivo imaging method for the early diagnosis of murine colitis with specificity for both genetic and experimental colitis. The said modality provides continuous measurements of reactive oxygen and nitrogen species (RONS) and minimizes the use of an increased number of experimental animals by using a luminal derivative chemiluminescent probe, L-012 which provides a cost-effective tool to study the level and longitudinal progression of colitis.