High added value of a population-based participatory surveillance system for community acute gastrointestinal, respiratory and influenza-like illnesses in Sweden, 2013-2014 using the web.

In 2013-2014, the Public Health Agency of Sweden developed a web-based participatory surveillance system, Hӓlsorapport, based on a random sample of individuals reporting symptoms weekly online, to estimate the community incidence of self-reported acute gastrointestinal (AGI), acute respiratory (ARI) and influenza-like (ILI) illnesses and their severity. We evaluated Hӓlsorapport's acceptability, completeness, representativeness and its data correlation with other surveillance data. We calculated response proportions and Spearman correlation coefficients (r) between (i) incidence of illnesses in Hӓlsorapport and (ii) proportions of specific search terms to medical-advice website and reasons for calling a medical advice hotline. Of 34 748 invitees, 3245 (9·3%) joined the cohort. Participants answered 81% (139 013) of the weekly questionnaires and 90% (16 351) of follow-up questionnaires. AGI incidence correlated with searches on winter-vomiting disease [r = 0·81, 95% confidence interval (CI) 0·69-0·89], and ARI incidence correlated with searches on cough (r = 0·77, 95% CI 0·62-0·86). ILI incidence correlated with the web query-based estimated incidence of ILI patients consulting physicians (r = 0·63, 95% CI 0·42-0·77). The high response to different questionnaires and the correlation with other syndromic surveillance systems suggest that Hӓlsorapport offers a reasonable representation of AGI, ARI and ILI patterns in the community and can complement traditional and syndromic surveillance systems to estimate their burden in the community.

The liver X receptor (LXR) and its target gene ABCA1 are regulated upon low oxygen in human trophoblast cells: a reason for alterations in preeclampsia?

OBJECTIVES: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in the human placenta under normal physiological circumstances and in preeclampsia. STUDY DESIGN: We investigated the expression pattern of the LXRs and their target genes in the human placenta during normal pregnancy and in preeclampsia. Placental explants and cell lines were studied under different oxygen levels and pharmacological LXR agonists. MAIN OUTCOME MEASURES: Gene expressions (Taqman PCR) and protein levels (Western Blot) were combined with immunohistochemistry to analyze the expression of LXR and its target genes. RESULTS: In the human placenta, LXRA and LXRB expression increased during normal pregnancy. This was paralleled by the expression of their prototypical target genes, e.g., the cholesterol transporter ABCA1. Interestingly, early-onset preeclamptic placentae revealed a significant upregulation of ABCA1. Culture of JAr trophoblast cells and human first trimester placental explants under low oxygen lead to increased expression of LXRA and ABCA1 which was further enhanced by the LXR agonist T0901317. CONCLUSIONS: LXRA together with ABCA1 are specifically expressed in the human placenta and can be regulated by hypoxia. Deregulation of this system in early preeclampsia might be the result of placental hypoxia and hence might have consequences for maternal-fetal cholesterol transport.

Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism.

Cholesterol is critical for several cellular functions and essential for normal fetal development. Therefore, its metabolism is tightly controlled during all life stages. The liver X receptors-alpha (LXRalpha; NR1H3) and -beta (LXRbeta; NR1H2) are nuclear receptors that are of key relevance in coordinating cholesterol and fatty acid metabolism. The aim of this study was to elucidate whether fetal cholesterol metabolism can be influenced in utero via pharmacological activation of LXR and whether this would have long-term effects on cholesterol homeostasis. Administration of the LXR agonist T0901317 to pregnant mice via their diet (0.015% wt/wt) led to induced fetal hepatic expression levels of the cholesterol transporter genes Abcg5/g8 and Abca1, higher plasma cholesterol levels, and lower hepatic cholesterol levels compared with controls. These profound changes during fetal development did not affect cholesterol metabolism in adulthood nor did they influence coping with a high-fat/high-cholesterol diet. This study shows that the LXR system is functional in fetal mice and susceptible to pharmacological activation. Despite massive changes in fetal cholesterol metabolism, regulatory mechanisms involved in cholesterol metabolism return to a "normal" state in offspring and allow coping with a high-fat/high-cholesterol diet.

Cholesterol transport by the placenta: placental liver X receptor activity as a modulator of fetal cholesterol metabolism?

Cholesterol is an important sterol in mammals. Defects in cholesterol synthesis or intracellular routing have devastating consequences already in utero: the Smith-Lemli-Opitz syndrome, desmosterolosis and Niemann-Pick C1 disease provide examples of severe human inherited diseases caused by mutations in cholesterol metabolism genes. On the other hand, elevated plasma cholesterol concentrations are associated with the development of atherosclerosis which represents a major health risk in Western societies. Moreover, several studies indicate that development of atherosclerosis may already start during fetal life. Hence, a carefully balanced regulation of cholesterol metabolism appears of critical importance for both the development of the fetus and health of the adult. In the adult, the liver X receptor is a key regulator of cholesterol metabolism. Its target genes regulate cellular cholesterol efflux and thereby modulate whole-body cholesterol fluxes. LXR and several of its target genes have recently been demonstrated to be expressed in the placenta, which would provide a means to control delivery of maternal cholesterol to the fetus. Here we discuss the potential role of the placenta in the regulation of fetal cholesterol homeostasis and strategies to influence maternal-fetal cholesterol transfer.

Dietary amino acids fed in free form and as protein components do not differently affect postprandial plasma insulin, glucagon, growth hormone and corticosterone responses in rats.

This study examined, whether the postprandial fate of dietary amino acids from different amino acid sources is regulated by the responses of insulin, glucagon, corticosterone and growth hormone (GH). Male Wistar rats were cannulated in the vena jugularis and assigned to dietary groups. The diets contained 21% casein or the same amino acids in free form. In the free amino acid diets, methionine level was varied between the groups. The feed was supplied in two distinct meals. In previous experiments it was established that oxidative amino acid losses of the free amino acid diets and protein diets were different. After 3 weeks on those diets, it appeared that the differences in postprandial oxidative losses had been diminished. GH was measured every 12 min, from 144 min before the start of the experimental meal over the following 144 min. Insulin and corticosterone were measured six times from the start of the meal until 270 min after the meal. No differences have been observed between the hormonal responses to both meals at day 5 and at day 26. In conclusion, it has been found that the differences in the oxidative losses between protein and free amino acid meals are not mediated by the combined action of the insulin, glucagon, corticosterone and GH. Postprandial catabolism of amino acids is most probably regulated by substrate induction.

Electronic reporting improves timeliness and completeness of infectious disease notification, The Netherlands, 2003.

In 2002, the internet based reporting system OSIRIS was introduced in the Netherlands and by the end of that year had fully replaced the paper-based reporting system. The objectives of OSIRIS were to improve timeliness and completeness of surveillance data on infectious diseases reported from regional to national level. We compared the timeliness of infectious diseases reported by the conventional paper-based system in 2001 with those reported by OSIRIS in 2003. Two distinct types of delay were compared: (1) total delay: defined as time between symptom onset and reporting at national level and (2) central delay: defined as time between regional and national reporting. Median delays between both systems were compared using the Wilcoxon Rank Sum-Test. We also compared electronic reports received via OSIRIS in 2003 to those received through the conventional system for 2001 for completeness of specific data fields. The Fisher exact test and the Mantel-Haenzel test with Yates correction were used to determine the significance of proportions of completed data fields in each system. Results showed the median central delay was significantly reduced for all diseases in OSIRIS compared to conventional reporting system. Overall, the median central delay was reduced from 10 days (interquartile range 4) in 2001 to 1 day (interquartile range 1) in 2003. Except for cases of malaria, the total delay, from symptom onset to national reporting, was also significantly reduced. In addition, OSIRIS records contained more complete information than conventional records. In total, in 2003, 92.3% of data field examined were complete compared with 81.3% in 2001. This study documents the benefits of electronic reporting of infectious disease surveillance data in terms of improved timeliness and completeness.

Electronic reporting improves timeliness and completeness of infectious disease notification, The Netherlands, 2003.

In 2002, the internet based reporting system OSIRIS was introduced in the Netherlands and by the end of that year had fully replaced the paper-based reporting system. The objectives of OSIRIS were to improve timeliness and completeness of surveillance data on infectious diseases reported from regional to national level. We compared the timeliness of infectious diseases reported by the conventional paper-based system in 2001 with those reported by OSIRIS in 2003. Two distinct types of delay were compared: total delay: defined as time between sympton onset and reporting at national level and central delay: defined as time between regional and national reporting. Median delays between both systems were compared using the Wilcoxon Rank Sum-Test. We also compared electronic reports received via OSIRIS in 2003 to those received through the conventional system for 2001 for completeness of specific data fields. The Fisher exact test and the Mantel-Haenzel test with Yates correction were used to determine the significance of proportions of completed data fields in each system.