Exposure to Perflouroalkyl acids and foetal and maternal thyroid status: a review

Background Exposure to perfluorinated-alkyl-acids (PFAAs) is ubiquitous. PFAAs are hormone-disrupting compounds that are strongly suspected to affect mother-child-health such as fetal growth. Thyroid disruption is a plausible mechanism of action. We aim to summarize the epidemiological evidence for the relation between prenatal and postnatal exposure to PFAAs and disruption of thyroid homeostasis in mothers and/or infants. Method Fifteen original publications on PFAAs concentrations and thyroid hormones (TH) in pregnant women and/or infants were found upon a literature search in the PubMed database. Information on exposure to seven PFAAs congeners [Perfluorooctane sulfonate (PFOS), Perfluorooctanoate (PFOA), Perfluorohexane sulfonate (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA), Perfluoroundecanoic acid (PFUnA), and Perfluorododecanoic acid (PFDoA)] and thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3), T3RU (Free triiodothyronine resin uptake) and FT4-index (FT4I) levels were recorded. We evaluated sampling of maternal TH by trimester, and infant TH by sex stratification. Reported associations between mother or infant PFAAs and TH were not uniformly assessed in the selected studies. Results Ten out of the fifteen studies examined maternal PFAAs concentration and TSH level. Seven studies showed significant associations between TSH and exposure to six PFAAs congeners, most of them were positive. Maternal T4 and T3 were investigated in nine studies and five studies found inverse associations between exposure to six PFAAs congeners and TH (TT3, TT4, FT3, FT4 and FT4I) levels. Eight of the fifteen studies investigated PFAAs concentrations and infant TSH. Infant TSH level was significantly affected in four studies, positively in three studies. Nine studies investigated infant T4 and T3 and seven studies found significant associations with PFAAs exposure. However, both inverse and positive significant associations with infant TH were found eliciting no clear direction. Conclusion Results indicate a mainly positive relationship between maternal PFAAs concentrations and TSH levels, and suggestion of an inverse association with T4 and/or T3 levels. Associations of infant TH with PFAAs concentration were less consistent.Det Frie Forskningsrad (DFF) 30531European Unions' Horizon 2020 research and innovation Programme 733032 HBM4E

Reduced use of antimicrobials after vaccination of pigs against porcine proliferative enteropathy in a Danish SPF herd

The present study explored whether the use of group medication with antibiotics in a Danish pig herd was reduced after vaccination of the pigs against proliferative enteropathy (PE) caused by Lawsonia intracellularis. 7900 pigs originating from a single commercial sow herd were vaccinated against L. intracellularis, whereas 7756 pigs were kept as non-vaccinated controls. The pigs were included batch-wise in the study with every second batch being vaccinated. In the vaccinated batches, the consumption of oxytetracykline to treat PE was reduced by 79%, with a significantly lower number of pigs being treated (P < 0.0001). Vaccination also resulted in a highly significant improvement of average daily weight gain (+ 46 g/day; P = 9.55 × 10-31) and carcase weight (+ 1.25 kg; P = 4.54 × 10-05) as well as a shortened fattening period (-8 days; P = 2.01 × 10-45)

A Highly Selective Cc Chemokine Receptor (Ccr)8 Antagonist Encoded by the Poxvirus Molluscum Contagiosum

The MC148 CC chemokine from the human poxvirus molluscum contagiosum (MCV) was probed in parallel with viral macrophage inflammatory protein (vMIP)-II encoded by human herpesvirus 8 (HHV8) in 16 classified human chemokine receptors. In competition binding using radiolabeled endogenous chemokines as well as radiolabeled MC148, MC148 bound with high affinity only to CCR8. In calcium mobilization assays, MC148 had no effect on its own on any of the chemokine receptors, but in a dose-dependent manner blocked the stimulatory effect of the endogenous I-309 chemokine on CCR8 without affecting chemokine-induced signaling of any other receptor. In contrast, vMIP-II acted as an antagonist on 10 of the 16 chemokine receptors, covering all four classes: XCR, CCR, CXCR, and CX3CR. In chemotaxis assays, MC148 specifically blocked the I-309–induced response but, for example, not stromal cell–derived factor 1α, monocyte chemoattractant protein 1, or interleukin 8–induced chemotaxis. We thus concluded that the two viruses choose two different ways to block the chemokine system: HHV8 encodes the broad-spectrum chemokine antagonist vMIP-II, whereas MCV encodes a highly selective CCR8 antagonist, MC148, conceivably to interfere with monocyte invasion and dendritic cell function. Because of its pharmacological selectivity, the MC148 protein could be a useful tool in the delineation of the role played by CCR8 and its endogenous ligand, I-309

Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial

SummaryObjectiveTo investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA).MethodsData from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into ‘Unloaders’ (participants that reduced joint loads) and ‘Loaders’ (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period.Results157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: −2.4 KOOS points [95% CI −6.8:1.9]) and cartilage loss (group difference: −0.06 BLOKS points [95% CI −0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders.ConclusionFor obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads.Clinicaltrials.govNCT00655941

Increasing water intake in pre-school children with unhealthy drinking habits: a year-long controlled longitudinal field experiment assessing the impact of information, water affordance, and social regulation

Objective We investigated the effect of three interventions to increase the plain water consumption of children with unhealthy drinking habits, with an innovative approach combining the three layers of Installation Theory: embodied competences, affordances and social regulation. Methods 334 preschool children and their carers were allocated to three interventions: Control (control): no intervention, Information (info): online coaching sessions on water health benefits aiming at modifying embodied competences (knowledge), Information + Water Affordance (info + w): the same plus home delivery of small bottles of water. After three months, half of the info and info + w subjects were allocated to Social Regulation (+social) (on-line discussion forum) or no further intervention (-social). Intake of plain water and all other fluid types of the children were recorded by the carers 6 times over a year using an online 7-day fluid-specific dietary record.Results Over 1 year, all groups significantly increased daily water consumption by 3.0–7.8 times (+118 to +222 mL). Info + w + social and Info-social generated the highest increase in plain water intake after one year compared to baseline, by 7.8 times (+216 mL) and 6.7 times (+222 mL) respectively; both significantly exceeded the control (3.0 times, +118 mL), whilst the effect of info + w-social (5.0 times, +158 mL) and info + social (5.3 times, +198 mL) did not differ from that of control. All groups saw a decrease of sweetened beverages intake, again with info + w + social generating the largest decrease (−27%; −172 mL). No changes in other fluids or total fluid intake were observed. Conclusions Sustainable increased water consumption can be achieved in children with unhealthy drinking habits by influencing representations, changing material affordances, and providing social regulation. Combining the three provided the strongest effect as predicted by Installation Theory

Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 Ϯ 1 years (mean Ϯ SEM), BMI 27 Ϯ 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P &lt; 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue

High concentrations of lead (Pb) in blood and milk of free-ranging brown bears (Ursus arctos) in Scandinavia

Exposure to lead (Pb) is a global health problem for both humans and wildlife. Despite a dramatic decline in human Pb exposure following restrictions of leaded gasoline and industry and thereby an overall reduction of Pb entering the environment, Pb exposure continues to be a problem for wildlife species. Literature on scavenging terrestrial mammals, including interactions between Pb exposure and life history, is however limited. We quantified Pb concentration in 153 blood samples from 110 free-ranging Scandinavian brown bears (Ursus arctos), 1-25 years old, using inductively coupled plasma sector field mass spectrometry. We used generalized linear models to test effects of age, body mass, reproduction status and spatial distribution on the blood Pb concentrations of 56 female bears. We sampled 28 females together with 56 dependent cubs and paired their blood Pb concentrations. From 20 lactating females, we measured the Pb concentration in milk. The mean blood Pb concentration was 96.6 mu g/L (range: 38.7-220.5 mu g/L). Both the mean and range are well above established threshold concentrations for developmental neurotoxicity (12 mu g/L), increased systolic blood pressure (36 mu g/L) and prevalence of kidney disease in humans (15 mu g/L). Lactating females had higher Pb blood concentrations compared to younger, non-lactating females. Blood Pb concentrations of dependent cubs were correlated with their mother's blood Pb concentration, which in turn was correlated with the Pb concentration in the milk. Life-long Pb exposure in Scandinavian brown bears may have adverse effects both on individual and population levels. The high blood Pb concentrations found in brown bears contrast the general reduction in environmental Pb contamination over the past decades in Scandinavia and more research is needed to identify the sources and pathways of Pb exposure in the brown bears