The intention to make preconception lifestyle changes in men: Associated socio-demographic and psychosocial factors.

OBJECTIVE: To determine which socio-demographic and psychosocial factors are associated with the intention for preconception healthily behavioral changes in the general population of reproductive-aged men. DESIGN: A cross-sectional, multicenter study. SETTING: Four secondary schools, 4 Public Centers for Social Welfare, 7 Community Health Centers, and online. All data was collected in the X. PARTICIPANTS: A convenience sample of 304 reproductive-aged men were recruited between July 2015 and July 2016. MEASUREMENTS AND FINDINGS: An existing questionnaire was adapted and validated to assess the intention, self-efficacy, attitude, social influence, knowledge, and barriers towards 10 preconception health behaviors. Simple and multiple logistic and linear regression analyses were performed. The overall intention to make preconception lifestyle changes was high (median score: 0.7 on the 0-1 scale). The multiple linear regression revealed that self-efficacy (p < 0.001), social influence of the close social environment (p = 0.02), and attitude (p = 0.05) were associated with a higher intention score. Experiencing negative emotions and beliefs about pre-pregnancy preparations was associated with less intention for preconception health behaviors (p = 0.001). None of the socio-demographic factors was significantly associated with the intention score. KEY CONCLUSIONS: The overall intention to make preconception lifestyle changes was high, and associated with different psychosocial factors including self-efficacy, social influence, and attitude. IMPLICATIONS FOR PRACTICE: Preconception interventions should target the identified factors to improve preconception health behaviors in men and negative emotions and beliefs about preconception. Interventions about preconception health care should primarily suggest that men bear the same responsibility as women, which will address the current gender politics and could have -in second instance- a positive outcome on pregnancy outcomes. Because socio-demographic characteristics were of no influence, a general approach should be used.

Barriers and facilitators to the provision of preconception care by healthcare providers: A systematic review.

BACKGROUND: Healthcare providers play an important role in providing preconception care to women and men of childbearing age. Yet, the provision of preconception care by healthcare providers remains low. OBJECTIVES: To provide an overview of barriers and facilitators at multiple levels that influence the provision of preconception care by healthcare providers. DESIGN: A mixed-methods systematic review. DATA SOURCES: PubMed, Web of Science, CINAHL, The Cochrane Library, and EMBASE were systematically searched up to April 27, 2017. The search strategy contained MeSH terms and key words related to preconception care and healthcare providers. Reference lists of included studies and systematic reviews on preconception care were screened. REVIEW METHODS: Publications were eligible if they reported on barriers and facilitators influencing the provision of preconception care by healthcare providers. Data were extracted by two independent reviewers using a data extraction form. Barriers and facilitators were organized based on the social ecological model. The methodological quality of included studies was evaluated using the Critical Appraisal Skills Programme Qualitative checklist for qualitative studies, the Quality Assessment Tool for quantitative studies, and the Mixed Methods Appraisal Tool for mixed methods studies. RESULTS: Thirty-one articles were included. Barriers were more reported than facilitators. These were situated at provider level (unfavourable attitude and lack of knowledge of preconception care, not working in the field of obstetrics and gynaecology, lack of clarity on the responsibility for providing preconception care) and client level (not contacting a healthcare provider in the preconception stage, negative attitude, and lack of knowledge of preconception care). Limited resources (lack of time, tools, guidelines, and reimbursement) were frequently reported at the organizational and societal level. CONCLUSIONS: Healthcare providers reported more barriers than facilitators to provide preconception care, which might explain why the provision of preconception care is low. To overcome the different client, provider, organizational, and societal barriers, it is necessary to develop and implement multilevel interventions.

Psychometric properties of the Dutch version of the London Measure of Unplanned Pregnancy in women with pregnancies ending in birth.

OBJECTIVE: To evaluate the psychometric properties of the Dutch version of the London Measure of Unplanned Pregnancy in women with pregnancies ending in birth. METHODS: A two-phase psychometric evaluation design was set-up. Phase I comprised the translation from English into Dutch and pretesting with 6 women using cognitive interviews. In phase II, the reliability and validity of the Dutch version of the LMUP was assessed in 517 women giving birth recently. Reliability (internal consistency) was assessed using Cronbach's alpha, inter-item correlations, and corrected item-total correlations. Construct validity was assessed using principal components analysis and hypothesis testing. Exploratory Mokken scale analysis was carried out. RESULTS: 517 women aged 15-45 completed the Dutch version of the LMUP. Reliability testing showed acceptable internal consistency (alpha = 0.74, positive inter-item correlations between all items, all corrected item-total correlations >0.20). Validity testing confirmed the unidimensional structure of the scale and all hypotheses were confirmed. The overall Loevinger's H coefficient was 0.57, representing a 'strong' scale. CONCLUSION: The Dutch version of the LMUP is a reliable and valid measure that can be used in the Dutch-speaking population in Belgium to assess pregnancy planning. Future research is necessary to assess the stability of the Dutch version of the LMUP, and to evaluate its psychometric properties in women with abortions.

Preconception lifestyle changes in women with planned pregnancies.

OBJECTIVES: (1) to study preconception lifestyle changes and associated factors in women with planned pregnancies; (2) to assess the prevalence of risk factors for adverse pregnancy outcomes in women not reporting any preconception lifestyle changes; and (3) to explore the need for and use of preconception-related advice. DESIGN: secondary data analysis of a cross-sectional study about pregnancy planning. SETTING: six Flemish Hospitals (Belgium). PARTICIPANTS: four hundred and thirty women with a planned pregnancy ending in birth. MEASUREMENTS: preconception lifestyle changes were measured during the first 5 days postpartum using the validated London Measure of Unplanned Pregnancy. The following changes were assessed: folic acid or multivitamin intake, smoking reduction or cessation, alcohol reduction or cessation, caffeine reduction or cessation, eating more healthily, achieving a healthier weight, obtaining medical or health advice, or another self-reported preconception lifestyle change. FINDINGS: most women (83%) that planned their pregnancy reported ≥1 lifestyle change in preparation for pregnancy. Overall, nulliparous women (OR 2.18, 95% CI 1.23-3.87) and women with a previous miscarriage (OR 2.44, 95% CI 1.14-5.21) were more likely to prepare for pregnancy, while experiencing financial difficulties (OR 0.20, 95% CI 0.04-0.97) or having a lower educational level (OR 0.56, 95% CI 0.32-0.99) decreased the likelihood of preparing for pregnancy. Half of the women (48%) obtained advice about preconception health, and 86% of these women received their advice from a professional caregiver. Three-quarters (77%) of the women who did not improve their lifestyle before conceiving reported one or more risk factors for adverse pregnancy outcomes. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: multiparous women and women of lower socio-economic status were less likely to change their lifestyle before conception. Strategies to promote preconception health in these women need to be tailored to their needs and characteristics to overcome barriers to change. It may be advantageous to reach these women through non-medical channels, such as schools or other community organizations.

Blood protein biomarkers as diagnostic tool for ischemic stroke: a systematic review.

AIM: This systematic review provides a summary of the blood protein biomarkers that have been studied for the diagnosis of acute ischemic stroke. MATERIALS & METHODS: An extensive MEDLINE (using PubMed) and Web of Knowledge search was performed. From the 354 articles found, 42 were eligible for further analysis and 25 protein biomarkers were examined. RESULTS: Though many candidate blood-based protein biomarkers were examined, only two could significantly differentiate ischemic stroke patients from healthy controls, stroke mimics and hemorrhagic stroke patients. CONCLUSION: The blood protein biomarkers, brain natriuretic peptide (BNP) and S100B, were promising biomarkers in diagnosing ischemic stroke. They could be used in cases of diagnostic uncertainty and/or when less experienced healthcare personnel are involved.

Advanced midwifery practice: An evolutionary concept analysis.

AIM: the concept of 'advanced midwifery practice' is explored to a limited extent in the international literature. However, a clear conception of advanced midwifery practice is vital to advance the discipline and to achieve both internal and external legitimacy. This concept analysis aims to clarify advanced midwifery practice and identify its components. METHODS: a review of the literature was executed using Rodgers' evolutionary method of concept analysis to analyze the attributes, references, related terms, antecedents and consequences of advanced midwifery practice. RESULTS: an international consensus definition of advanced midwifery practice is currently lacking. Four major attributes of advanced midwife practitioners (AMPs) are identified: autonomy in practice, leadership, expertise, and research skills. A consensus was found on the need of preparation at master's level for AMPs. Such midwives have a broad and internationally varied scope of practice, fulfilling different roles such as clinicians, clinical and professional leaders, educators, consultants, managers, change agents, researchers, and auditors. Evidence illustrating the important part AMPs play on a clinical and strategic level is mounting. KEY CONCLUSIONS: the findings of this concept analysis support a wide variety in the emergence, titles, roles, and scope of practice of AMPs. Research on clinical and strategic outcomes of care provided by AMPs supports further implementation of these roles. As the indistinctness of AMPs' titles and roles is one of the barriers for implementation, a clear conceptualization of advanced midwifery practice seems essential for successful implementation. IMPLICATIONS FOR PRACTICE: an international debate and consensus on the defining elements of advanced midwifery practice could enhance the further development of midwifery as a profession and is a prerequisite for its successful implementation. Due to rising numbers of AMPs, extension of practice and elevated quality requirements in healthcare, more outcomes research exclusively evaluating the contribution of AMPs to healthcare becomes possible and desirable.

Preconception-related needs of reproductive-aged women.

OBJECTIVE: to assess women׳s interest in preconception care, their organisational preferences, and their preconception-related information and support needs. DESIGN: cross-sectional study design. SETTING: participants were recruited online through social media and discussion forums for issues relating to (in)fertility, pregnancy and parenting, and at the Women׳s Clinic of Ghent University Hospital. PARTICIPANTS: 242 reproductive-aged women with a desire to have (more) children. FINDINGS: the majority of women (75%) wanted to receive preconception care in the future. Gynaecologists (93%) were the preferred source of preconception care, followed by midwives (73%) and general practitioners (63%). Most women wanted information about lifestyle, environmental exposures, working conditions and medical issues. Information needs were higher among women with (history of) mental illness [odds ratio (OR) 3.50, 95% confidence interval (CI) 1.08-11.36], (history of) eye and otolaryngological problems (OR 2.22, 95% CI 0.95-5.21) and overweight (OR 2.22, 95% CI 1.01-4.93). A few women indicated that they needed preconception-related support. Overweight women reported greater need for lifestyle-related support compared with women of healthy weight (p=0.001). KEY CONCLUSIONS: reproductive-aged women are interested in preconception care, and would prefer to receive this care directly from a professional caregiver. Most women had high preconception-related information needs and lower support needs. IMPLICATIONS FOR PRACTICE: although women reported that they would prefer to receive preconception care from gynaecologists, the results indicate that midwives can also play an important role in the provision of preconception care. They would need further training to improve their knowledge, skills and awareness regarding preconception care.

Communication difficulties and the experience of loneliness in patients with cancer dealing with fertility issues: a qualitative study.

PURPOSE/OBJECTIVES: To explore communication difficulties and the experience of loneliness among patients with cancer dealing with fertility issues. DESIGN: Qualitative study based on grounded theory principles. SETTING: One university hospital and two general hospitals in Flanders, Belgium. SAMPLE: 21 female and 7 male patients with cancer with potential fertility problems as a result of treatment. METHODS: Grounded theory approach using the constant comparison method; data collection (semistructured face-to-face interviews) and analysis occurred simultaneously. FINDINGS: Loneliness was a central theme in the experience of potential fertility loss among patients with cancer. Feelings of loneliness resulted from communication difficulties between the patient and members of his or her social environment or healthcare professionals because of several underlying processes and influencing factors. CONCLUSIONS: Loneliness was a strong and common feeling among patients with cancer. Patients, members of their social environment, and healthcare professionals experienced difficulties in communicating about fertility in the context of cancer, leading to patients' feelings of loneliness. IMPLICATIONS FOR NURSING: Healthcare professionals must be attentive to signs indicating loneliness regarding fertility concerns, and they should provide adequate information and appropriate guidance to support patients. Professionals need further training to improve knowledge and skills.

Combination of therapeutic hypothermia and other neuroprotective strategies after an ischemic cerebral insult.

Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the "ischemic cascade") that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. This review provides an overview of all neuroprotective strategies that have been combined with therapeutic hypothermia in rodent models of focal cerebral ischemia. A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.

Cancer patients' and professional caregivers' needs, preferences and factors associated with receiving and providing fertility-related information: a mixed-methods systematic review.

OBJECTIVES: Cancer treatment can impair fertility. The aim of this review was to investigate (1) fertility information needs, receipt and provision, (2) fertility information preferences, and (3) factors associated with receiving/providing fertility information. Cancer patients' and professional caregivers' perspectives were considered. DESIGN: Mixed-methods systematic review. DATA SOURCES: Six electronic databases (PubMed, Web of Science, CINAHL, CRD, Embase) were systematically screened to retrieve articles published between January 2001 and March 2012. Reference lists and conference abstracts were checked for additional publications. REVIEW METHODS: The principles outlined in the Cochrane Handbook for Systematic Reviews of Intervention were applied. Publications were included if they explored fertility-related information/communication in cancer patients/survivors of reproductive age or professional caregivers. The Critical Appraisal Skills Programme for Qualitative Studies and the Quality Assessment Tool for Quantitative Studies were used to assess the methodological quality. A standardised form based on the Cochrane guidelines for systematic reviews was used to extract the data. Two independent reviewers performed all methodological steps. RESULTS: Of the 1872 papers found, 27 were included in this review. The majority (66-100%) of the cancer patients wanted information about the impact of cancer therapy on fertility. The need and importance were higher in younger and childless patients, and in patients having childbearing plans. The number of patients receiving this information ranged from 0% to 85%. Several factors were associated with the lack of information receipt, including female gender and age 35 years or older. Patients preferred information via an individual consultation. In the diagnostic phase patients needed information about the impact of the treatment on fertility and preservation options. At the end or after the treatment, information needs shifted towards long term effects. Professional caregivers experienced several barriers in providing fertility information, including caregiver-, patient- and institutional-related factors. Nurses in particular, perceived difficulty in providing fertility-related information due to additional barriers associated with limited responsibility and opportunity in fertility information provision. CONCLUSION: Professional caregivers experienced multiple barriers that hinder information provision. Further exploration of the role of Advanced Nurse Practitioners/Midwifes and the development of an evidence based intervention to overcome caregiver-related barriers are recommended to improve information provision.

Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens.

Mycotoxins lead to economic losses in animal production. A way to counteract mycotoxicosis is the use of detoxifiers. The European Food Safety Authority stated that the efficacy of detoxifiers should be investigated based on toxicokinetic studies. Little information is available on the absolute oral bioavailability and the toxicokinetic parameters of deoxynivalenol, T-2 and zearalenone in broilers. Toxins were administered intravenously and orally in a two-way cross-over design. For deoxynivalenol a bolus of 0.75mg/kg BW was administered, for T-2 toxin 0.02mg/kg BW and for zearalenone 0.3mg/kg BW. Blood was collected at several time points. Plasma levels of the mycotoxins and their metabolite(s) were quantified using LC-MS/MS methods and toxicokinetic parameters were analyzed. Deoxynivalenol has a low absolute oral bioavailability (19.3%). For zearalenone and T-2 no plasma levels above the limit of quantification were observed after an oral bolus. Volumes of distribution were recorded, i.e. 4.99, 0.14 and 22.26L/kg for deoxynivalenol, T-2 toxin and zearalenone, respectively. Total body clearance was 0.12, 0.03 and 0.48L/minkg for deoxynivalenol, T-2 toxin and zearalenone, respectively. After IV administration, T-2 toxin had the shortest elimination half-life (3.9min), followed by deoxynivalenol (27.9min) and zearalenone (31.8min).

Porcine intestinal epithelial barrier disruption by the Fusarium mycotoxins deoxynivalenol and T-2 toxin promotes transepithelial passage of doxycycline and paromomycin.

BACKGROUND: The gastrointestinal tract is the first target for the potentially harmful effects of mycotoxins after intake of mycotoxin contaminated food or feed. With deoxynivalenol (DON), T-2 toxin (T-2), fumonisin B1 (FB1) and zearalenone (ZEA) being important Fusarium toxins in the northern hemisphere, this study aimed to investigate in vitro the toxic effect of these mycotoxins on intestinal porcine epithelial cells derived from the jejunum (IPEC-J2 cells). Viability of IPEC-J2 cells as well as the proportion of apoptotic and necrotic IPEC-J2 cells was determined by flow cytometry after 72 h of exposure to the toxins. Correlatively, the integrity of the intestinal epithelial cell monolayer was studied using Transwell(®) inserts, in which the trans-epithelial electrical resistance (TEER) and passage of the antibiotics doxycycline and paromomycin were used as endpoints. RESULTS: We demonstrated that the percentage of Annexin-V-FITC and PI negative (viable) cells, Annexin-V-FITC positive and PI negative (apoptotic) cells and Annexin-V-FITC and PI positive (necrotic) IPEC-J2 cells showed a mycotoxin concentration-dependent relationship with T-2 toxin being the most toxic. Moreover, the ratio between Annexin-V-FITC positive and PI negative cells and Annexin-V-FITC and PI positive cells varied depending on the type of toxin. More Annexin-V-FITC and PI positive cells could be found after treatment with T-2 toxin, while more Annexin-V-FITC positive and PI negative cells were found after exposure to DON. Consistent with the cytotoxicity results, both DON and T-2 decreased TEER and increased cellular permeability to doxycycline and paromomycin in a time- and concentration-dependent manner. CONCLUSIONS: It was concluded that Fusarium mycotoxins may severely disturb the intestinal epithelial barrier and promote passage of antibiotics.

A modified glucomannan mycotoxin-adsorbing agent counteracts the reduced weight gain and diminishes cecal colonization of Salmonella Typhimurium in T-2 toxin exposed pigs.

The aim of the study was to investigate the effect of a modified glucomannan binder on the course of a Salmonella Typhimurium infection in pigs. Therefore, four pig diets were provided during 23 days: (1) free of mycotoxins, (2) containing 1g binder per kg feed, (3) containing 83 µg T-2 toxin per kg feed and (4) containing 83 µg T-2 toxin and 1g binder per kg feed. After 18 days, all pigs were inoculated with Salmonella Typhimurium and euthanized five days later. The addition of the binder to T-2 toxin contaminated feed counteracted the reduced weight gain of pigs caused by T-2 toxin and reduced the amount of Salmonella Typhimurium in the cecum and cecal contents. In vitro findings might indicate that the binder captures Salmonella. We thus conclude that the binder counteracts T-2 toxin induced weight loss and possibly binds Salmonella, resulting in a reduced cecal colonization.

Interaction between tylosin and bentonite clay from a pharmacokinetic perspective.

The interaction between bentonite and tylosin was investigated in broiler chickens, based on pharmacokinetic characteristics obtained in vivo. Simultaneous oral administration of bentonite and tylosin significantly lowered plasma levels of tylosin and reduced the area under the plasma concentration-time curve (AUC(0-inf)), maximal plasma concentration (C(max)), time to maximal plasma concentration (T(max)) and relative oral bioavailability. The results prove unambiguously the binding of tylosin by bentonite. Simultaneous administration of tylosin (in the drinking water or feed) and bentonite (mixed in the feed as a mycotoxin binder) should therefore be avoided.

Influence of mycotoxins and a mycotoxin adsorbing agent on the oral bioavailability of commonly used antibiotics in pigs.

It is recognized that mycotoxins can cause a variety of adverse health effects in animals, including altered gastrointestinal barrier function. It is the aim of the present study to determine whether mycotoxin-contaminated diets can alter the oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and whether a mycotoxin adsorbing agent included into diets interacts with those antibiotics. Experiments were conducted with pigs utilizing diets that contained blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol), mycotoxin-contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed supplemented with mycotoxin binder. Diets with T-2 toxin and binder or deoxynivalenol and binder induced increased plasma concentrations of doxycycline administered as single bolus in pigs compared to diets containing blank feed. These results suggest that complex interactions may occur between mycotoxins, mycotoxin binders, and antibiotics which could alter antibiotic bioavailability. This could have consequences for animal toxicity, withdrawal time for oral antibiotics, or public health.

The association between malnutrition and oral health status in elderly in long-term care facilities: a systematic review.

OBJECTIVES: Malnutrition is a common problem in the elderly. It is not clear if oral health is associated to malnutrition in this population. The aim of this systematic review is to determine whether an association exists between oral health and malnutrition in the elderly in a long-term care facility. DESIGN: Systematic review. DATA SOURCE: Medline, Cochrane and Cinahl were systematically searched for to identify articles published between January 1985 and May 2011. Reference lists were checked for additional publications. REVIEW METHODS: Publications were included if they explored the association between oral health status and malnutrition. As no consensus about terminology was found, a sensitive filter was developed. The methodological quality of the studies was assessed. Two independent reviewers performed all methodological steps. RESULTS: Sixteen studies met the criteria for inclusion. Eleven studies used a multivariate approach; nine of these found an association between oral health status and malnutrition. Four studies found a relationship between masticatory problems and malnutrition. Five studies found an association between malnutrition and dental condition, number of oral problems, tongue alteration, problems with saliva flow, and candidiasis. Overall, the methodological quality of the studies was medium. CONCLUSIONS: Tentative evidence indicates an independent association between oral health status and malnutrition in the elderly residing in a long-term care facility. Caution is needed for the interpretation of these results because of the absence of a gold standard to define and assess malnutrition and oral health status and the presence of methodological limitations throughout the studies.

T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions.

The mycotoxin T-2 toxin and Salmonella Typhimurium infections pose a significant threat to human and animal health. Interactions between both agents may result in a different outcome of the infection. Therefore, the aim of the presented study was to investigate the effects of low and relevant concentrations of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. We showed that the presence of 15 and 83 µg T-2 toxin per kg feed significantly decreased the amount of Salmonella Typhimurium bacteria present in the cecum contents, and a tendency to a reduced colonization of the jejunum, ileum, cecum, colon and colon contents was noticed. In vitro, proteomic analysis of porcine enterocytes revealed that a very low concentration of T-2 toxin (5 ng/mL) affects the protein expression of mitochondrial, endoplasmatic reticulum and cytoskeleton associated proteins, proteins involved in protein synthesis and folding, RNA synthesis, mitogen-activated protein kinase signaling and regulatory processes. Similarly low concentrations (1-100 ng/mL) promoted the susceptibility of porcine macrophages and intestinal epithelial cells to Salmonella Typhimurium invasion, in a SPI-1 independent manner. Furthermore, T-2 toxin (1-5 ng/mL) promoted the translocation of Salmonella Typhimurium over an intestinal porcine epithelial cell monolayer. Although these findings may seem in favour of Salmonella Typhimurium, microarray analysis showed that T-2 toxin (5 ng/mL) causes an intoxication of Salmonella Typhimurium, represented by a reduced motility and a downregulation of metabolic and Salmonella Pathogenicity Island 1 genes. This study demonstrates marked interactions of T-2 toxin with Salmonella Typhimurium pathogenesis, resulting in bacterial intoxication.

The mycotoxin deoxynivalenol potentiates intestinal inflammation by Salmonella typhimurium in porcine ileal loops.

BACKGROUND AND AIMS: Both deoxynivalenol (DON) and nontyphoidal salmonellosis are emerging threats with possible hazardous effects on both human and animal health. The objective of this study was to examine whether DON at low but relevant concentrations interacts with the intestinal inflammation induced by Salmonella Typhimurium. METHODOLOGY: By using a porcine intestinal ileal loop model, we investigated whether intake of low concentrations of DON interacts with the early intestinal inflammatory response induced by Salmonella Typhimurium. RESULTS: A significant higher expression of IL-12 and TNFα and a clear potentiation of the expression of IL-1ß, IL-8, MCP-1 and IL-6 was seen in loops co-exposed to 1 µg/mL of DON and Salmonella Typhimurium compared to loops exposed to Salmonella Typhimurium alone. This potentiation coincided with a significantly enhanced Salmonella invasion in and translocation over the intestinal epithelial IPEC-J2 cells, exposed to non-cytotoxic concentrations of DON for 24 h. Exposure of Salmonella Typhimurium to 0.250 µg/mL of DON affected the bacterial gene expression level of a limited number of genes, however none of these expression changes seemed to give an explanation for the increased invasion and translocation of Salmonella Typhimurium and the potentiated inflammatory response in combination with DON. CONCLUSION: These data imply that the intake of low and relevant concentrations of DON renders the intestinal epithelium more susceptible to Salmonella Typhimurium with a subsequent potentiation of the inflammatory response in the gut.

Herpes simplex virus type 1 penetrates the basement membrane in human nasal respiratory mucosa.

BACKGROUND: Herpes simplex virus infections are highly prevalent in humans. However, the current therapeutics suffer important drawbacks such as limited results in neonates, increasing occurrence of resistance and impeded treatment of stromal infections. Remarkably, interactions of herpesviruses with human mucosa, the locus of infection, remain poorly understood and the underlying mechanisms in stromal infection remain controversial. METHODOLOGY/PRINCIPAL FINDINGS: A human model consisting of nasal respiratory mucosa explants was characterised. Viability and integrity were examined during 96 h of cultivation. HSV1-mucosa interactions were analysed. In particular, we investigated whether HSV1 is able to reach the stroma. Explant viability and integrity remained preserved. HSV1 induced rounding up and loosening of epithelial cells with very few apoptotic and necrotic cells observed. Following 16-24 h of infection, HSV1 penetrated the basement membrane and replicated in the underlying lamina propria. CONCLUSIONS/SIGNIFICANCE: This human explant model can be used to study virus-mucosa interactions and viral mucosal invasion mechanisms. Using this model, our results provide a novel insight into the HSV1 stromal invasion mechanism and for the first time directly demonstrate that HSV1 can penetrate the basement membrane.