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1.
Hum Reprod ; 36(5): 1416-1426, 2021 04 20.
Article in English | MEDLINE | ID: mdl-33313698

ABSTRACT

STUDY QUESTION: Are live birth (LB) and perinatal outcomes affected by the use of frozen own versus frozen donor oocytes? SUMMARY ANSWER: Treatment cycles using frozen own oocytes have a lower LB rate but a lower risk of low birth weight (LBW) as compared with frozen donor oocytes. WHAT IS KNOWN ALREADY: A rising trend of oocyte cryopreservation has been noted internationally in the creation of donor oocyte banks and in freezing own oocytes for later use in settings of fertility preservation and social egg freezing. Published literature on birth outcomes with frozen oocytes has primarily utilised data from donor oocyte banks due to the relative paucity of outcome data from cycles using frozen own oocytes. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study utilising the anonymised database of the Human Fertilisation and Embryology Authority, which is the statutory regulator of fertility treatment in the UK. We analysed 988 015 IVF cycles from the Human Fertilisation and Embryology Authority (HFEA) register from 2000 to 2016. Perinatal outcomes were assessed from singleton births only. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three clinical models were used to assess LB and perinatal outcomes: Model 1 compared frozen own oocytes (n = 632) with frozen donor oocytes (n = 922); Model 2 compared frozen donor oocytes (n = 922) with fresh donor oocytes (n = 24 706); Model 3 compared first cycle of fresh embryo transfer from frozen donor oocytes (n = 917) with first cycle of frozen embryo transfer created with own oocytes and no prior fresh transfer (n = 326). Preterm birth (PTB) was defined as LB before 37 weeks and LBW as birth weight <2500 g. Adjustment was performed for confounding variables such as maternal age, number of embryos transferred and decade of treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The LB rate (18.0% versus 30.7%; adjusted odds ratio (aOR) 0.61, 95% CI 0.43-0.85) and the incidence of LBW (5.3% versus 14.0%; aOR 0.29, 95% CI 0.13-0.90) was significantly lower with frozen own oocytes as compared with frozen donor oocytes with no significant difference in PTB (9.5% versus 15.7%; aOR 0.56, 95% CI 0.26-1.21). A lower LB rate was noted in frozen donor oocyte cycles (30.7% versus 34.7%; aOR 0.69, 95% CI 0.59-0.80) when compared with fresh donor oocyte cycles. First cycle frozen donor oocytes did not show any significant difference in LB rate (30.1% versus 19.3%; aOR 1.26, 95% CI 0.86-1.83) or PTB, but a higher incidence of LBW (17.7% versus 5.4%; aOR 3.77, 95% CI 1.51-9.43) as compared with first cycle frozen embryos using own oocytes. LIMITATIONS, REASONS FOR CAUTION: The indication for oocyte freezing, method of freezing used (whether slow-freezing or vitrification) and age at which eggs where frozen were unavailable. We report a subgroup analysis of women using their own frozen oocytes prior to 37 years. Cumulative LB rate could not be assessed due to the anonymous nature of the dataset. WIDER IMPLICATIONS OF THE FINDINGS: Women planning to freeze their own eggs for fertility preservation or social egg freezing need to be counselled that the results from frozen donor egg banks may not completely apply to them. However, they can be reassured that oocyte cryopreservation does not appear to have a deleterious effect on perinatal outcomes. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The authors have no relevant conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Live Birth , Premature Birth , Cryopreservation , Female , Fertilization , Fertilization in Vitro , Humans , Infant, Newborn , Oocytes , Pregnancy , Premature Birth/epidemiology , Retrospective Studies
2.
Reprod Biomed Online ; 39(5): 764-769, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31615725

ABSTRACT

RESEARCH QUESTION: Does a woman's ethnicity affect her fresh and frozen embryo transfer outcomes differently? DESIGN: A retrospective cohort study of the first fresh and first frozen embryo transfer per woman carried out at a single tertiary level fertility unit between 2010 and 2016 using data retrieved from an electronic database. Biochemical pregnancy, biochemical pregnancy loss, clinical pregnancy, miscarriage and live birth rates per embryo transfer were compared between 5876 white Caucasian, 1071 South Asian and 114 Black Afro-Caribbean women undergoing their first fresh embryo transfer and for 1418 Caucasian, 273 South Asian and 31 Afro-Caribbean women undergoing their first frozen embryo transfer. Logistic regression was used to adjust for age, number of oocytes retrieved, and number and stage of embryos transferred. RESULTS: South Asian (26% versus 32%, adjusted OR 0.622, 95% CI 0.533 to 0.725) and Black Afro-Caribbean women (21% versus 32%, adjusted OR 0.528, 95% CI 0.332 to 0.839) had a lower live birth rate per fresh embryo transfer compared with white Caucasian women. In contrast, the live birth rates per frozen embryo transfer were not significantly different between South Asian and Caucasian women (26% versus 28%, adjusted OR 0.890, 95% CI 0.661 to 1.200) and between Afro-Caribbean and Caucasian women (29% versus 28%, adjusted OR 0.983, 95% CI 0.447 to 2.162). CONCLUSION: South Asian and Black Afro-Caribbean women have a significantly lower live birth rate than white Caucasian women after fresh embryo transfer, but their frozen embryo transfer live birth rates are not significantly different.


Subject(s)
Embryo Transfer/methods , Ethnicity , Infertility/ethnology , Adult , Asia , Asian People , Black People , Caribbean Region , Cryopreservation , Female , Fertilization in Vitro/methods , Humans , Pregnancy , Pregnancy Outcome , Pregnancy Rate , Retrospective Studies , Sperm Injections, Intracytoplasmic , United Kingdom/ethnology
3.
Epidemiol Infect ; 147: e280, 2019 09 27.
Article in English | MEDLINE | ID: mdl-31558173

ABSTRACT

Enteric illness outbreaks are complex events, therefore, outbreak investigators use many different hypothesis generation methods depending on the situation. This scoping review was conducted to describe methods used to generate a hypothesis during enteric illness outbreak investigations. The search included five databases and grey literature for articles published between 1 January 2000 and 2 May 2015. Relevance screening and article characterisation were conducted by two independent reviewers using pretested forms. There were 903 outbreaks that described hypothesis generation methods and 33 papers which focused on the evaluation of hypothesis generation methods. Common hypothesis generation methods described are analytic studies (64.8%), descriptive epidemiology (33.7%), food or environmental sampling (32.8%) and facility inspections (27.9%). The least common methods included the use of a single interviewer (0.4%) and investigation of outliers (0.4%). Most studies reported using two or more methods to generate hypotheses (81.2%), with 29.2% of studies reporting using four or more. The use of multiple different hypothesis generation methods both within and between outbreaks highlights the complexity of enteric illness outbreak investigations. Future research should examine the effectiveness of each method and the contexts for which each is most effective in efficiently leading to source identification.


Subject(s)
Communicable Disease Control/methods , Disease Outbreaks , Epidemiologic Methods , Gastrointestinal Diseases/epidemiology , Humans
4.
Biomech Model Mechanobiol ; 18(3): 829-843, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30635851

ABSTRACT

During vaginal delivery women sustain stretching of their pelvic floor, risking tissue injury and adverse outcomes. Since studies in pregnant women are limited with ethical constraints, computational models have become an interesting alternative to elucidate the pregnancy mechanisms. This research investigates the uterine contractions during foetus expulsion without an imposed trajectory. Such physical process is captured by means of a chemo-mechanical constitutive model, where the uterine contractions are triggered by chemical stimuli. The foetus descent, which includes both pushing and resting stages, has a descent rate within the physiological range. Moreover, the behaviour of the foetus and the uterus stretch agree well with clinical data presented in the literature. The follow-up of this study will be to obtain a complete childbirth simulation, considering also the pelvic floor muscles and its supporting structures. The simulation of a realistic rate of descent, including the pushing and resting stages, is of significant importance to study the pelvic floor muscles due to their viscoelastic nature.


Subject(s)
Computer Simulation , Fetus/physiology , Models, Biological , Uterine Contraction/physiology , Biomechanical Phenomena , Finite Element Analysis , Humans , Kinetics , Muscle, Smooth/physiology , Myosins/metabolism , Parturition/physiology , Phosphorylation , Stress, Mechanical
5.
BJOG ; 126(2): 280-286, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29443441

ABSTRACT

OBJECTIVE: Comparison of live birth rates and the perinatal outcomes after fresh and frozen embryo transfer between time-lapse imaging (TLI) and standard culture (SC) incubators. DESIGN: Retrospective cohort study. SETTING: A single tertiary level IVF unit. POPULATION: Women undergoing IVF between January 2014 and October 2015. METHODS: Comparison was done between 1064 IVF cycles using TLI (TLI cycles) and 818 IVF cycles using SC (SC cycles). MAIN OUTCOME MEASURES: Cumulative live birth rate per oocyte retrieval and perinatal outcomes including birthweight, gestational age, preterm birth (PTB) (<37 weeks), early preterm birth (PTB; <32 weeks), low birthweight (LBW; <2500 g), very LBW (<1500 g) and macrosomia (>4500 g). RESULTS: The fresh embryo transfer live birth rate was noted to be higher for TLI cycles [TLI 36.8 versus SC 33.9%, adjusted odds ratio (aOR) 1.28, 95% CI 1.05-1.57], but the frozen embryo transfer live birth rates were not significantly different. The mean birthweight was higher in the TLI group after both fresh [adjusted mean difference (aMD) 174.78 g, 95% CI 64.80-284.77] and frozen embryo transfers (aMD 175.91 g, 95% CI 16.98-334.84). After a fresh embryo transfer, there was a lower risk of early PTB and very LBW in the TLI group. Among frozen embryo transfers, there was a lower risk of early PTB and LBW in the TLI group. CONCLUSIONS: TLI incubators are associated with improved perinatal outcomes and higher mean birthweight after fresh and frozen embryo transfer. TWEETABLE ABSTRACT: Time-lapse imaging incubators in IVF improve perinatal outcomes after both fresh and frozen embryo transfers.


Subject(s)
Birth Rate , Embryo Culture Techniques/instrumentation , Embryo Transfer/methods , Incubators , Time-Lapse Imaging , Adult , Birth Weight , Cryopreservation/statistics & numerical data , Embryo Transfer/statistics & numerical data , Female , Humans , Pregnancy , Pregnancy Outcome/epidemiology , Retrospective Studies
6.
Epidemiol Infect ; 147: e66, 2018 Dec 05.
Article in English | MEDLINE | ID: mdl-30516125

ABSTRACT

Urbanisation and climate change are altering the pattern of California serogroup viruses in North America. As La Crosse virus (LACV) is the most pathogenic of the California serogroup, it is important to identify changes in distribution, transmission and pathogenesis. A scoping review (ScR) was prioritised to summarise the global evidence on LACV. A comprehensive search strategy was used, identified references were screened for relevance and relevant articles were characterised. Each step was conducted by two independent reviewers using pre-tested forms. Analysis identified areas of research saturation and gaps. The ScR included 481 research articles that were mostly journal articles (78.2%) conducted in North America (90.9%) from 1969 to 2016. Most evidence focused on epidemiology (44.9%), virus characteristics (25.8%), transmission conditions (18.7%) and pathogenesis of LACV in hosts (18.3%). Fewer studies evaluated the accuracy of diagnostic tests (8.7%), the efficacy of treatments (3.5%), prevention and control strategies (3.1%), the economic burden of infection (0.6%) and social impact (0.2%) of LACV. None of the literature predicted the impact of climate change on LACV, nor were any cases reported in Canada. These findings are intended to guide research to close knowledge gaps and inform evidence-based decisions surrounding activities for the prevention and control of LACV.

7.
Environ Monit Assess ; 190(9): 564, 2018 Aug 31.
Article in English | MEDLINE | ID: mdl-30167796

ABSTRACT

Tropical coastal lagoons are highly productive environments exhibiting high biodiversity. However, the use of these ecosystems by local communities is of concern, since this generally leads to environmental degradation. The Imboassica coastal lagoon, located in Macaé city, in Northern Rio de Janeiro, is an important ecosystem in the state, however, already displaying signs of anthropogenic impacts. Carnivorous fish Hoplias malabaricus specimens were sampled from this impacted site, as well as from a reference area. Fish from Imboassica Lagoon presented lower condition factor, lower cholinesterase activity, and higher percentage of erythrocyte micronuclei when compared to fish from the reference site. Metals in fish from Imboassica Lagoon were always higher than Encantada Lagoon, with some seasonal differences, where some metals were higher in the rainy season compared to the dry season in muscle tissue, with the exception of Cu, Fe, Sr, and Zn; and in the liver, except for Ba, Cd, Cr, Ni, and Sr. Cr and Mn in the edible muscle portion of the fish were higher than the limits established by Brazilian and International legislations as permissible for human consumption, thus leading to concerns regarding public health risks for the local population that use fish as their main protein source.


Subject(s)
Ecosystem , Environmental Exposure/adverse effects , Fishes/metabolism , Metals, Heavy/metabolism , Seafood/analysis , Seawater , Water Pollutants, Chemical/metabolism , Animals , Biomarkers/metabolism , Brazil , Cholinesterases/metabolism , Environmental Exposure/analysis , Environmental Monitoring/methods , Erythrocytes , Humans , Liver/metabolism , Micronuclei, Chromosome-Defective , Muscles/metabolism , Rain , Seasons , Tropical Climate
8.
Can Commun Dis Rep ; 44(10): 243-256, 2018 Oct 04.
Article in English | MEDLINE | ID: mdl-31524886

ABSTRACT

Lyme disease (LD) is an emerging infectious disease in Canada associated with expansion of the geographic range of the tick vector Ixodes scapularis in eastern and central Canada. A scoping review of published research was prioritized to identify and characterize the scientific evidence concerning key aspects of LD to support public health efforts. Prior to initiation of this review, an expert advisory group was surveyed to solicit insight on priority topics and scope. A pre-tested search strategy implemented in eight databases (updated September 2016) captured relevant research. Pre-tested screening and data characterization forms were completed by two independent reviewers and descriptive analysis was conducted to identify topic areas with solid evidence and knowledge gaps. Of 19,353 records screened, 2,258 relevant articles were included in the review under the following six public health focus areas: a) surveillance/monitoring in North America (n=809); b) evaluation of diagnostic tests (n=736); c) risk factors (n=545); d) public health interventions (n=205); e) public knowledge, attitudes and/or perceptions in North America (n=202); and f) the economic burden of LD or cost-benefit of interventions (n=32). The majority of research investigated Borrelia burgdorferi (n=1,664), humans (n=1,154) and Ixodes scapularis (n=459). Sufficient research was identified for potential systematic reviews in four topic areas: a) accuracy of diagnostic tests; b) risk factors for human illness; c) efficacy of LD intervention strategies; and d) prevalence and/or incidence of LD in humans or B. burgdorferi sensu stricto in vertebrate reservoirs or ticks in North America. Future primary research could focus on closing knowledge gaps, such as the role of less studied vertebrate reservoirs in the transmission cycle. Results of this scoping review can be used to quickly identify and summarize relevant research pertaining to specific questions about LD or B. burgdorferi sensu lato in humans, vertebrate hosts or vectors, providing evidence-informed information within timelines that are conducive for public health decision-making.

9.
Transbound Emerg Dis ; 65(1): 37-49, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28139079

ABSTRACT

A number of prion diseases affect humans, including Creutzfeldt-Jakob disease; most of these are due to genetic mutations in the affected individual and occur sporadically, but some result from transmission of prion proteins from external sources. Of the known animal prion diseases, only bovine spongiform encephalopathy prions have been shown to be transmissible from animals to humans under non-experimental conditions. Chronic wasting disease (CWD) is a prion disease that affects cervids (e.g., deer and elk) in North America and isolated populations in Korea and Europe. Systematic review methodology was used to identify, select, critically appraise and analyse data from relevant research. Studies were evaluated for adherence to good conduct based on their study design following the Cochrane collaboration's approach to grading the quality of evidence and the strength of recommendations (GRADE). Twenty-three studies were included after screening 800 citations from the literature search and evaluating 78 full papers. Studies examined the transmissibility of CWD prions to humans using epidemiological study design, in vitro and in vivo experiments. Five epidemiological studies, two studies on macaques and seven studies on humanized transgenic mice provided no evidence to support the possibility of transmission of CWD prions to humans. Ongoing surveillance in the United States and Canada has not documented CWD transmission to humans. However, two studies on squirrel monkeys provided evidence that transmission of CWD prions resulting in prion disease is possible in these monkeys under experimental conditions and seven in vitro experiments provided evidence that CWD prions can convert human prion protein to a misfolded state. Therefore, future discovery of CWD transmission to humans cannot be entirely ruled out on the basis of current studies, particularly in the light of possible decades-long incubation periods for CWD prions in humans. It would be prudent to continue CWD research and epidemiologic surveillance, exercise caution when handling potentially contaminated material and explore CWD management opportunities.


Subject(s)
Prions/physiology , Wasting Disease, Chronic/transmission , Animals , Canada/epidemiology , Cattle , Deer , Europe/epidemiology , Humans , Mice , Mice, Transgenic , North America/epidemiology , Republic of Korea/epidemiology
10.
Zoonoses Public Health ; 62(4): 269-84, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25175882

ABSTRACT

Wildlife can contribute to environmental contamination with bacterial pathogens and their transfer to the human food chain. Global usage and frequent misuse of antimicrobials contribute to emergence of new antimicrobial resistant (AMR) strains of foodborne pathogens. We conducted a scoping review of published research to identify and characterize the evidence on wildlife's role in transmission of AMR and/or bacterial pathogens to the food chain. An advisory group (AG) of 13 North American experts from diverse disciplines was surveyed to solicit insight in the review scope, priority topics and research characteristics. A pre-tested search strategy was implemented in seven bibliographic databases (1990 to January 2013). Citations were relevance screened, and key characteristics on priority topics extracted independently by two reviewers. Analysis identified topic areas with solid evidence and main knowledge gaps. North America reported 30% of 866 relevant articles. The prevalence of five targeted bacterial pathogens and/or AMR in any pathogen in wildlife was reported in 582 articles. Transmission risk factors for selected bacteria or AMR in any bacteria were reported in 300. Interventions to control transmission were discussed in 124 articles and formally evaluated in 50. The majority of primary research investigated birds, cervids, rodents, feral pigs, opossums, E. coli (n = 329), Salmonella (n = 293) and Campylobacter (n = 124). An association between wildlife and transmission of bacterial pathogens and/or AMR to the food chain was supported in 122 studies. The scoping review identified a significant body of research on the role of wild birds in the prevalence and transmission of E. coli, Salmonella and Campylobacter. There was little research employing molecular methods contributing to the evidence concerning the importance and direction of transmission of wildlife/pathogen combinations. Given the advancements of these methods, future research should focus in this area to help prioritize future intervention studies and risk mitigation strategies.


Subject(s)
Animals, Wild/microbiology , Bacterial Infections/transmission , Environmental Exposure/adverse effects , Food Chain , Food Microbiology , Animals , Anti-Bacterial Agents/adverse effects , Bacterial Infections/epidemiology , Drug Resistance, Bacterial , Humans , Prevalence , Risk Factors
13.
Acta Reumatol Port ; 36(1): 14-9, 2011.
Article in English | MEDLINE | ID: mdl-21483275

ABSTRACT

AIM: To study the association of serotonin transporter gene polymorphisms and osteoporosis. MATERIAL AND METHODS: Blood samples were collected from 186 individuals with normal bone mineral density and 89 with osteoporosis. Serotonin transporter gene polymorphisms 5HTTVNTR and 5HTTLPR were studied by PCR and statistical analyses used to test the association between groups. RESULTS: The frequency of 12/10 and 12/12 genotypes of 5HTTVNTR was significantly higher among the osteoporotic patients (OR=2,620 CI 95% [1,112--6,172], P=0,037). For 5HTTLPR we did not find significant differences between the two studied groups. CONCLUSIONS: As far as we know, this is one of the few studies that report an association between 5HTTVNTR and osteoporosis opening the hypothesis that the determination of this specific serotonin transporter gene polymorphism may contribute to the identification of individuals at high risk for the development of osteoporosis.


Subject(s)
Osteoporosis/genetics , Polymorphism, Genetic , Serotonin Plasma Membrane Transport Proteins/genetics , Female , Humans , Male , Middle Aged
14.
J Public Health (Oxf) ; 33(2): 223-33, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20935133

ABSTRACT

OBJECTIVE: The objective is to systematically estimate the current cancer incidence and mortality from the six leading cancer types globally and by sub-regions resulting from exposure to known risk factors such as tobacco use, elevated body weight, alcohol consumption, inadequate physical activity, unhealthy diet and infections. METHODS: Cancer incidence, mortality and burden of disease caused by the main cancer risk factors were calculated using comparative risk assessment methods and updated data on mortality and risks. RESULTS: Lung cancer was the most common cancer in men and breast cancer the most common cancer in women, both in terms of incidence and mortality. The five leading behavioral and dietary risks--high body mass index, low fruit and vegetable intake, physical inactivity, tobacco use and alcohol use--were responsible for 24% of new cancer cases and 30% of cancer deaths. Cancers with the largest proportions attributable to preventable risk factors were cervical cancer (100%) and lung cancer (71%). Seventy percent of liver cancers and 60% of stomach cancers were due to infectious agents. A higher proportion of cancer deaths was attributed to infections in low- and middle-income than in high-income countries. CONCLUSIONS: The cancer burden is driven by changes in exposure to influential risk factors and can be influenced by preventive interventions aimed at reducing these exposures.


Subject(s)
Neoplasms/etiology , Neoplasms/mortality , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Diet/adverse effects , Female , Health Behavior , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/virology , Overweight/complications , Registries , Risk Assessment , Risk Factors , Sex Distribution , Smoking/adverse effects , Virus Diseases/complications , World Health Organization , Young Adult
15.
Dig Liver Dis ; 41(2): 123-6, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18723413

ABSTRACT

BACKGROUND AND AIMS: Complete colonoscopy is critical for the evaluation of many paediatric gastrointestinal diseases. The aim of the study was to investigate the feasibility of magnetic positioning device for paediatric colonoscopy and to compare completion rate and procedure time with and without the device. METHODS: Prospective randomised controlled trial of standard colonoscopy compared to magnetic positioning device assisted colonoscopy in children and adolescents ages 7-20 years was performed. RESULTS: Analysis showed that the proportion of successfully completed colonoscopies were 19/20 (95%) in the MP arm versus 17/18 (94.4%) in the SC arm, p=NS. The median time to complete colonoscopy to the cecum was 16.5 min (range 6-52 min) in the MP arm and 12 min (range 6-33 min) in the SC arm, p=NS. CONCLUSIONS: Our preliminary data suggest that the use of magnetic positioning device for colonoscopy is feasible in paediatric patients. These data suggest that the use of magnetic positioning device may not be of benefit for experienced endoscopists who achieved very high colonoscopy completion rates without the MP device. Further studies are needed to determine its role in paediatric colonoscopy since this device may be of more benefit for physicians in training.


Subject(s)
Colonoscopes , Colonoscopy/methods , Magnetics/instrumentation , Pediatrics/instrumentation , Pediatrics/methods , Adolescent , Child , Equipment Design , Feasibility Studies , Female , Humans , Male , Pilot Projects , Prospective Studies , Young Adult
16.
Gut ; 57(3): 374-82, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17965061

ABSTRACT

BACKGROUND AND AIMS: Reticulo-endothelial macrophages together with duodenal enterocytes coordinate body iron homeostasis. The aim of this study was to investigate the regulatory actions of the hormone hepcidin on ferroportin expression in these two cell types. METHODS: We investigated the in vitro effects of hepcidin in well-characterised human cell culture models of macrophages (differentiated THP-1 cells) and intestinal epithelial cells (Caco-2 cells). The in vivo effects of hepcidin were also investigated in mice injected with a synthetic hepcidin peptide. RESULTS: Exposure to hepcidin (presented either as conditioned medium from interleukin-6-stimulated HuH7 cells or as a synthetic peptide) resulted in a rapid (within 4 h) decrease in ferroportin expression in THP-1 macrophages but had no effect on ferroportin levels in Caco-2 cells. To determine whether these rapid effects of hepcidin were also evident in vivo we injected mice with a synthetic hepcidin peptide. Four hours post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were decreased significantly and the hepcidin-treated mice developed hypoferraemia. Interestingly, in the same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron transport. CONCLUSIONS: These data suggests that the rapid response to hepcidin is cell type and tissue specific. Upon its release, hepcidin initially targets macrophage iron recycling. The duodenum appears to be less sensitive to this initial rise in hepcidin levels. We believe the fact that macrophages respond more acutely to a hepcidin challenge is fully consistent with their central role in maintaining body iron homeostasis.


Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Intestinal Mucosa/drug effects , Macrophages/drug effects , Animals , Antimicrobial Cationic Peptides/biosynthesis , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/physiology , Biological Transport/drug effects , Caco-2 Cells , Cation Transport Proteins/metabolism , Coculture Techniques , Culture Media, Conditioned , Duodenum/metabolism , Epithelial Cells/drug effects , Hepcidins , Humans , Intestinal Mucosa/cytology , Iron/blood , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/genetics , Spleen/metabolism
17.
Gut ; 54(10): 1391-5, 2005 Oct.
Article in English | MEDLINE | ID: mdl-15914574

ABSTRACT

BACKGROUND: Despite the requirement for increased iron delivery for erythropoiesis during hypoxia, there is very little information on how duodenal iron uptake and its transfer to the blood adapts to this condition. AIMS: To assess the effects of 30 days of chronic hypoxia in rats on luminal iron uptake and transfer of the metal to blood, together with gene expression of hepcidin, a proposed negative regulator of iron transport. METHODS: 59-Fe uptake by isolated duodenum and its transfer to blood by in vivo duodenal segments was measured after exposure of rats to room air or 10% oxygen for four weeks. Liver hepcidin expression was measured by real time reverse transcription-polymerase chain reaction. The effects of hypoxia on hepcidin gene expression by HepG2 cells was also determined. RESULTS: Hypoxia did not affect villus length but enhanced (+192.6%) luminal iron uptake by increasing the rate of uptake by all enterocytes, particularly those on the upper villus. Hypoxia promoted iron transfer to the blood but reduced mucosal iron accumulation in vivo by 66.7%. Hypoxia reduced expression of hepcidin mRNA in both rat liver and HepG2 cells. CONCLUSIONS: Prolonged hypoxia enhances iron transport from duodenal lumen to blood but the process is unable to fully meet the iron requirement for increased erythropoiesis. Reduced secretion of hepcidin may be pivotal to the changes in iron absorption. The processes responsible for suppression of hepcidin expression are unknown but are likely to involve a direct effect of hypoxia on hepatocytes.


Subject(s)
Antimicrobial Cationic Peptides/metabolism , Duodenum/metabolism , Hypoxia/metabolism , Iron/pharmacokinetics , Animals , Antimicrobial Cationic Peptides/genetics , Cells, Cultured , Chronic Disease , Disease Models, Animal , Gene Expression Regulation/genetics , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Hepcidins , Hypoxia/genetics , Iron/blood , Liver/metabolism , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley
18.
Environ Manage ; 27(5): 705-14, 2001 May.
Article in English | MEDLINE | ID: mdl-11334158

ABSTRACT

In a recent paper, it was suggested that one of the reasons behind the decline in public regard toward British Columbia's environmental movement was an increasingly negative portrayal of them by the print media. To investigate this suggestion, we undertook a content analysis of print media reporting of forestry and environmental activities in the province's most widely read newspaper, the Vancouver Sun, during 1993 and 1997. We hypothesized that if the print media did contribute to the decline in public regard toward the environmental movement, we would find increasingly negative coverage of the environmental movement over the periods studied. We also hypothesized that this would be accompanied by a decrease in the frequency of articles dealing with issues consistent with the agenda of the environmental movement. We were not able to provide support for our initial hypothesis, nor did we observe a decrease in coverage emphasizing the environmental issues. We did, however, observe an increase in coverage of articles emphasizing typically proindustry issues with many more articles written with a proforestry slant in 1997 than articles written in 1993. This suggests that there had been an agenda shift from environmentally oriented concerns in British Columbia to those associated with the forest industry. As an explanation for the agenda shift, we point to changes in the management and reporting philosophy at the Vancouver Sun, the emergence of an organized, proindustry counterframing strategy by the BC Forest Alliance, and the implementation of several government policies aimed at regulating the activities of the forest industry.


Subject(s)
Conservation of Natural Resources , Forestry , Newspapers as Topic , Public Opinion , British Columbia , Commerce , Humans , Industry , Prejudice , Public Policy
19.
Eur J Hum Genet ; 9(11): 843-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11781701

ABSTRACT

An earlier study of reference values of iron parameters in Portugal showed significant differences between populations from northern and southern villages. This study addresses the question of the geographical distribution in Portugal of the two main mutations (C282Y and H63D) of the hereditary hemochromatosis gene, HFE. For that purpose, a stratified sample of 640 anonymous dried blood spot samples was randomly selected from the major regions of Portugal: North, Center, Lisbon and the Tagus Valley, Alentejo and Algarve. Differences in the geographical distribution of these two mutations were observed thus confirming the presumed differences between the age of the two mutations which is compatible with the postulated Celtic/Nordic origin of the C282Y mutation. The finding of a significantly higher allelic frequency of the C282Y mutation in the North (0.058) than in the South (0.009) could also point to an effect of differential selective forces acting in the different geographical areas of the country. Data on archaeological, ethnographic and linguistic records and on the North/South distribution of Portuguese cattle breeds of European or African origin have also been reported. In addition to their interest for population genetics, the results represent a reminder of the need to take into account regional differences in the design of strategies for population screening of hereditary hemochromatosis.


Subject(s)
HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Membrane Proteins , Mutation, Missense/genetics , DNA/genetics , Gene Frequency , Genotype , Geography , Hemochromatosis/genetics , Hemochromatosis Protein , Humans , Portugal
20.
Am J Gastroenterol ; 95(8): 1990-3, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10950047

ABSTRACT

OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.


Subject(s)
Colitis/complications , Colitis/diagnosis , Intestinal Polyps/complications , Intestinal Polyps/diagnosis , Adolescent , Biopsy , Child , Child, Preschool , Colon/pathology , Endoscopy , Female , Humans , Infant , Intestinal Mucosa/pathology , Intestinal Polyps/surgery , Intraoperative Period , Male , Medical Records , Recurrence , Retrospective Studies
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