Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Effect of laser biostimulation and a low-calorie diet vs. a low-calorie diet alone on insulin resistance, inflammatory biomarkers, and depression among obese postmenopausal women: a randomized controlled trial.

OBJECTIVE: Postmenopausal women are significantly predisposed to a multitude of disorders. Laser biostimulation (LB) and a healthy diet have been linked to multiple health benefits. This study aimed to investigate the effect of a combined LB and balanced low-calorie diet (LCD) vs. an LCD alone on insulin resistance (IR), inflammatory biomarkers, and depression score in obese postmenopausal women. PATIENTS AND METHODS: In the present study, a total of 66 postmenopausal women, with a mean age of 66.61 ± 4.80 years and a body mass index (BMI) of 35.93 ± 2.67 kg/m2, were randomized into two equal groups. The experimental group received LB and LCD (including 50-60% carbohydrates, 15-20% protein, 20-35% fat, and 25 g of fiber/day plus a restriction of 500-1000 kcal/d), while the control group followed the same diet program only for 12 weeks. Before and after the intervention, IR [measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR index)], inflammatory biomarkers [C-reactive protein (CRP), white blood cells (WBCs), lymphocytes, and erythrocyte sedimentation rate (ESR)], and depression level [as assessed by the Hamilton Depression Rating Scale (HAMD-17)] were all measured. RESULTS: Using an intention-to-treat analysis for 60 women who completed the study, the body weight average reduction was -13.14% for the experimental group (p<0.001) vs. -6.36% for the control group (p<0.001). BMI, IR, inflammatory markers, and depression levels were also similarly changed. CONCLUSIONS: In postmenopausal obese women, adding LB to a suitable dietary program provides the most significant benefit in terms of lowering IR, metabolic inflammation, and depression.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

[Features of the use of synthetic analogues of thyroid hormones: а 2020 THESIS* questionnaire survey of members of the Belarusian Public Medical Association of Endocrinology and Metabolism].

BACKGROUND: The standard treatment for hypothyroidism is levothyroxine (LT4), which in the Republic of Belarus is available in tablet form whereas liothyronine (LT3) is not registered, but patients can purchase them on their own abroad. AIM: This study aimed to investigate Belarusian endocrinologists' attitude of thyroid hormones in hypothyroid and euthyroid patients. MATERIALS AND METHODS: An online survey was conducted, for which members of the Belarusian Medical Association of Endocrinology and Metabolism were invited by posting information in the group chat and by e-mail. The research period was from October 1 to December 26, 2020. 210 questionnaires were received, 146 of which were used. RESULTS: The majority of participants, 145 (99.3%), indicated that they were using LT4 as the first-choice drug for the treatment hypothyroidism. Sixty-one (41.8%) doctors answered that LT3 + LT4 combination likely can be used in patients with long-term untreated hypothyroidism and 15 (10.3%) - in patients with persistent symptoms of hypothyroidism, despite biochemical euthyroidism on therapy LT4. Over half of the respondents 84 (57.5%) answered that thyroid hormone therapy was never indicated for euthyroid patients, but 50 (34.2%) would consider it for female infertility with high level of thyroid antibodies and 36 (24.7%) for simple goiter growing over time. In various conditions that could interfere with absorption of LT4, most responding Belarusian endocrinologists do not expect a significant difference with different formulations (tablets+"I do not expect major changes in different forms" vs. "soft gel capsules"+"liquid solution"; p <0.001). Persistent symptoms of hypothyroidism on the background of LT4 replacement therapy with the achievement of the target TSH can mainly be caused by psychosocial factors, concomitant diseases, unrealistic patient expectations, chronic fatigue syndrome, and the burden of chronic disease. CONCLUSION: The method of choice of Belarusian endocrinologists in the treatment of hypothyroidism is LT4 replacement therapy, but the appointment of LT4 + LT3 combination therapy can be considered in certain clinical situations. As a rule, endocrinologists do not prescribe LT4 in patients with euthyroidism and do not expect a significant difference when using other forms of levothyroxine.

Inequalities in education and national income are associated with poorer diet: Pooled analysis of individual participant data across 12 European countries.

BACKGROUND: Malnutrition linked to noncommunicable diseases presents major health problems across Europe. The World Health Organisation encourages countries to conduct national dietary surveys to obtain data to inform public health policies designed to prevent noncommunicable diseases. METHODS: Data on 27334 participants aged 19-64y were harmonised and pooled across national dietary survey datasets from 12 countries across the WHO European Region. Weighted mean nutrient intakes were age-standardised using the Eurostat 2013 European Standard Population. Associations between country-level Gross Domestic Product (GDP) and key nutrients and nutrient densities were investigated using linear regression. The potential mitigating influence of participant-level educational status was explored. FINDINGS: Higher GDP was positively associated with total sugar intake (5·0% energy for each 10% increase in GDP, 95% CI 0·6, 9·3). Scandinavian countries had the highest vitamin D intakes. Participants with higher educational status had better nutritional intakes, particularly within lower GDP countries. A 10% higher GDP was associated with lower total fat intakes (-0·2% energy, 95% CI -0·3, -0·1) and higher daily total folate intakes (14µg, 95% CI 12, 16) in higher educated individuals. INTERPRETATION: Lower income countries and lower education groups had poorer diet, particularly for micronutrients. We demonstrate for the first time that higher educational status appeared to have a mitigating effect on poorer diet in lower income countries. It illustrates the feasibility and value of harmonising national dietary survey data to inform European policy regarding access to healthy diets, particularly in disadvantaged groups. It specifically highlights the need for strong policies supporting nutritional intakes, prioritising lower education groups and lower income countries.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

OBJECTIVE: Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). METHODS: All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. RESULTS: Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were "psychosocial factors" and "burden of having to take medication", respectively. CONCLUSION: A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Antimicrobial susceptibility profiles of anaerobic bacteria, isolated from human clinical specimens, within different European and surrounding countries. A joint ESGAI study.

OBJECTIVES: Studies on the antimicrobial susceptibility profile of anaerobic bacteria are underrepresented in the literature. Within this study we aim to give an extensive overview of the differences in antimicrobial susceptibility profiles between different European and surrounding countries. METHODS: Minimal inhibitory concentration (MIC) data of different antibiotics were collected from 10 participating laboratories, representing an equal number of countries. All MIC's were determined using Etest, according to the protocol used by the participating laboratory. Anaerobic genera represented by at least 10 clinical isolates were included in the study. RESULTS: Each country tested different antibiotics, sometimes depending on the kind of infection and/or the anaerobic species isolated. All countries tested clindamycin and metronidazole. Resistance rates differed remarkably between the different countries. Especially in Kuwait, resistance was high for all tested antibiotics. Unexpected metronidazole resistance was observed for Finegoldia magna isolates, Peptoniphilus isolates and Eggerthella lenta isolates. CONCLUSIONS: Due to the extensive differences in antimicrobial susceptibility profile of anaerobic bacteria isolated within different countries, we strongly recommend to perform this kind of study on a regular basis.

Correction: S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Green synthesis and bactericidal activities of isotropic and anisotropic spherical gold nanoparticles produced using Peganum harmala L leaf and seed extracts.

Shape, size, and homogeneity affect the biological activity of gold nanoparticles (AuNPs) in nanomedicine and catalytic applications. Here we biosynthesized monodispersed isotropic and polydispersed anisotropic spherical AuNPs from leaf and seed extract broths of the medicinal plant Peganum harmala L. (Ph. L). Synthesized AuNPs were characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IRS), field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The antimicrobial activity of AuNPs against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) human pathogens was also assessed. Leaf- and seed-derived AuNPs had characteristic localized surface plasmon resonances of 530 and 578 nm, respectively. TEM, FE-SEM, EDX, and XRD revealed the formation of elemental face-centered cubic spherical monodispersed isotropic AuNPs of average size 43.44 nm and polydispersed anisotropic AuNPs of average size 52.04 nm from leaf and seed extract broths, respectively. FT-IR revealed polyphenols and alcohols as responsible for AuNP capping, reduction, and protection. Anisotropic AuNPs showed no antibacterial activity, whereas isotropic AuNPs showed good inhibition of both E. coli and S. aureus. This represents a simple and ecofriendly protocol for the green synthesis of monodispersed isotropic spherical AuNPs, which may have value in a variety of applications.

[Novel caped Pd nanoparticles-liquid chromatography-tandem mass spectrometry for the identification of oxygenates in Saudi Arabian crude oil].

Saudi Arabian crude oil is a super complex mixture and, up to now, there has been little research into its heteroatom-containing compounds.First, oxygenated compounds (OCs) were isolated from Saudi Arabian oil using a Pd nanoparticle exchange complex, which formed between the nano-Pds and the oxygenated ligands.Normally, polycyclic aromatic sulphur heterocycles (S-PAHs) are separated from petroleum oil via the same method.The obtained results reveal that all the OC formulations with S-PAHs can be separated from the pre-isolated aromatic fraction of crude oil via this approach.S-PAHs are mixtures of benzothiophene and dibenzothiophene congeners.The isolated OCs are composed mainly of hydroxyl compounds.The liquid chromatography (LC)/electrospray ionization (ESI) in positive ion mode ESI (+)/tandem mass spectrometry (MS/MS) technique was used to assign the molecular weight distribution and identify the isolated OCs.The LC/ESI (+)-MS/MS technique differentiates S-PAHs and OCs using protonated ions.Thus, LC/ESI (+)-MS/MS can be used to assign molecular weight distributions for both the groups as a single mixture.MS/MS in precursor ion mode was used for the immediate identification of the target S or O analytes.

How to isolate, identify and determine antimicrobial susceptibility of anaerobic bacteria in routine laboratories.

BACKGROUND: There has been increased interest in the study of anaerobic bacteria that cause human infection during the past decade. Many new genera and species have been described using 16S rRNA gene sequencing of clinical isolates obtained from different infection sites with commercially available special culture media to support the growth of anaerobes. Several systems, such as anaerobic pouches, boxes, jars and chambers provide suitable anaerobic culture conditions to isolate even strict anaerobic bacteria successfully from clinical specimens. Beside the classical, time-consuming identification methods and automated biochemical tests, the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has revolutionized identification of even unusual and slow-growing anaerobes directly from culture plates, providing the possibility of providing timely information about anaerobic infections. AIMS: The aim of this review article is to present methods for routine laboratories, which carry out anaerobic diagnostics on different levels. SOURCES: Relevant data from the literature mostly published during the last 7 years are encompassed and discussed. CONTENT: The review involves topics on the anaerobes that are members of the commensal microbiota and their role causing infection, the key requirements for collection and transport of specimens, processing of specimens in the laboratory, incubation techniques, identification and antimicrobial susceptibility testing of anaerobic bacteria. Advantages, drawbacks and specific benefits of the methods are highlighted. IMPLICATIONS: The present review aims to update and improve anaerobic microbiology in laboratories with optimal conditions as well as encourage its routine implementation in laboratories with restricted resources.

Gut microbiota modulates type I interferon and antibody-mediated immune responses in chickens infected with influenza virus subtype H9N2.

Commensal gut microbes play a critical role in shaping host defences against pathogens, including influenza viruses. The current study was conducted to assess the role and mechanisms of action of commensal gut microbiota on the innate and antibody-mediated responses of layer chickens against influenza virus subtype H9N2. A total of 104 one-day-old specific pathogen free chickens were assigned to either of the four treatments, which included two levels of antibiotics treatment (ABX- and ABX+) and two levels of H9N2 virus infection (H9N2- and H9N2+). At day 17 of age, chickens in the H9N2+ group were infected via the oral-nasal route with 400 µl of 107 TCID50/ml (200 µl/each route). Oropharyngeal and cloacal swabs at days 1, 3, 5, 7 and 9 post-infection (p.i.) for virus shedding, tissue samples at 12 h, 24 h and 36 h p.i. for mRNA measurement, and serum samples at days 7 and 14 p.i. for hemagglutination inhibition (HI) assay and IgG antibodies were collected. Virus shedding analysis showed that antibiotic treated (depleted)-H9N2 virus infected chickens showed a significantly higher oropharyngeal virus shedding at all time points, and cloacal shedding at days 3 and 5 p.i. compared to control treated (undepleted)-H9N2 infected chickens. Analysis of mRNA expression showed that infection of depleted chickens with H9N2 virus resulted in significantly down-regulated type I interferon responses both in the respiratory and gastrointestinal tracts compared to undepleted-H9N2 infected chickens. However, antibody-mediated immune response analysis showed a significantly higher HI antibody titre and IgG levels in the serum of chickens depleted with antibiotics and infected with H9N2 virus compared to undepleted-H9N2 infected chickens. In conclusion, findings from the current study suggest that the gut microbiota of chickens plays an important role in the initiation of innate responses against influenza virus infection, while the antibody-mediated immune response remains unaffected.

Influence of microclimate conditions on the cumulative exposure of nursery pigs to swine influenza A viruses.

The objective of this study was to investigate the association between environmental temperature and humidity and the presence of antibodies for two specific strains of swine influenza viruses: A/SW/ON/105-56/12/H3N2 (H3N2_D) and A/SW/ON/84/2012/H1N1 (H1N1_P). A cross-sectional study was performed in a commercial farm, and a total of 450 pigs at 10 weeks of age were blood sampled, by sampling 10 pigs per week for 45 weeks corresponding to 45 batches. Exposure of pigs to H3N2_D and H1N1_P virus was assessed by haemagglutination inhibition assay (HI), and a result of ≥1:40 was considered as indication of a positive exposure status for a specific strain. The selection of those two viruses was based on the fact that H1N1 was the dominant virus in Ontario herds, and H3N2 had been previously isolated in this particular farm. Environmental conditions were recorded through a portable device every 5 min and then summarized using descriptive statistics. The association between HI titres and environmental microconditions, in the nursery, was evaluated through random effect linear and logistic regression. The results showed that the prevalence for H1N1_P was high throughout the study (≥70%); however, for H3N2_D, the seroprevalence declined by the end of the study period. Results also showed an association between cumulative exposure to the viruses and temperature and relative humidity (p < .05). These results suggest that microclimate conditions can influence transmission patterns of influenza viruses in swine barns, and that even a herd with relatively simple demographics could have persistent and cocirculation of two different influenza A viruses IAV strains.

S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.

The Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR)s. S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by the PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells. Genes upregulated by the PI3-K pathway included the basic leucine zipper transcription factor, ATF-like 3 (BATF3), which is normally associated with the development of dendritic cells. Immunohistochemistry confirmed that BATF3 was expressed in HRS cells of most HL cases. In contrast, in normal lymphoid tissues, BATF3 expression was confined to a small fraction of CD30-positive immunoblasts. Knockdown of BATF3 in HL cell lines revealed that BATF3 contributed to the transcriptional programme of primary HRS cells, including the upregulation of S1PR1. Our data suggest that disruption of this potentially oncogenic feedforward S1P signalling loop could provide novel therapeutic opportunities for patients with HL.

A multi-center ring trial for the identification of anaerobic bacteria using MALDI-TOF MS.

Inter-laboratory reproducibility of Matrix Assisted Laser Desorption Time-of-Flight Mass Spectrometry (MALDI-TOF MS) of anaerobic bacteria has not been shown before. Therefore, ten anonymized anaerobic strains were sent to seven participating laboratories, an initiative of the European Network for the Rapid Identification of Anaerobes (ENRIA). On arrival the strains were cultured and identified using MALDI-TOF MS. The spectra derived were compared with two different Biotyper MALDI-TOF MS databases, the db5627 and the db6903. The results obtained using the db5627 shows a reasonable variation between the different laboratories. However, when a more optimized database is used, the variation is less pronounced. In this study we show that an optimized database not only results in a higher number of strains which can be identified using MALDI-TOF MS, but also corrects for differences in performance between laboratories.

Pathogenesis of spring viremia of carp virus in emerald shiner Notropis atherinoides Rafinesque, fathead minnow Pimephales promelas Rafinesque and white sucker Catostomus commersonii (Lacepede).

Spring viremia of carp (SVC) is a reportable disease to the World Organization of Animal Health (OIE) as it is known to cause significant international economic impact. In Canada, the first and only isolation of SVC virus (SVCV) was in 2006, from common carp Cyprinus carpio L., at Hamilton Harbour, Lake Ontario. The susceptibility of fathead minnow Pimephales promelas Rafinesque, emerald shiner Notropis atherinoides Rafinesque and white sucker Catostomus commersonii (Lacepede) to intraperitoneal injection of the Canadian isolate (HHOcarp06) was evaluated using experimental infection, virus isolation, quantitative reverse transcription polymerase chain reaction (qRT-PCR), histopathology and immunohistochemistry (IHC). Emerald shiner and fathead minnow were most susceptible with 43 and 53% cumulative mortality, respectively, compared with koi at 33%. Quantitative RT-PCR demonstrated that koi had high viral loads throughout the experiment. At 34 days post-infection, SVCV was detected from sampled emerald shiner and white sucker in very low titre and was not detected from fathead minnow. Koi, fathead minnow and emerald shiner had gross lesions typical of SVC disease. The histopathological picture was mostly dominated by necrotic changes in kidney, spleen, liver, pancreas and intestine. IHC further confirmed SVCV infection, and staining was largely correlated with histological lesions.

Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated. METHODS AND RESULTS: A cross-sectional descriptive study examining 98 stable adult patients with CCHD with a medical questionnaire, blood samples, MRI of the cerebrum (n=72), multidetector CT imaging (MDCT) of the thorax (n=76) and pulmonary scintigraphy (ventilation/perfusion/single-photon emission computerised tomography/CT) (n=66). The prevalence of cerebral infarction and pulmonary thrombosis according to imaging were 47% and 31%, respectively. Comparing the findings with previous medical history revealed a large under-reporting of thrombosis with only 22% of the patients having a clinical history of stroke and 25% of pulmonary thrombosis. There was no association between the degree of erythrocytosis or haemostatic abnormalities and the prevalence of thrombosis. CONCLUSIONS: Patients with CCHD have a prevalence of both cerebral and pulmonary thrombosis of around 30%-40%, which is much higher than that reported previously. Furthermore, there is a large discrepancy between clinical history and imaging findings, suggesting a high prevalence of silent thrombotic events. Neither erythrocytosis nor haemostatic abnormalities were associated with the prevalence of thrombosis in patients with CCHD. TRIAL REGISTRATION NUMBER: http://www.cvk.sum.dk/CVK/Home/English.aspx (H-KF-2006-4068).

In ovo delivery of Toll-like receptor 2 ligand, lipoteichoic acid induces pro-inflammatory mediators reducing post-hatch infectious laryngotracheitis virus infection.

Toll-like receptor (TLR) ligands are pathogen associated molecular patterns (PAMPs) recognized by the TLRs resulting in induction of host innate immune responses. One of the PAMPs that binds to TLR2 and cluster of differentiation (CD) 14 is lipotechoic acid (LTA), which activates downstream signals culminating in the release of pro-inflammatory cytokines. In this study, we investigated whether in ovo LTA delivery leads to the induction of antiviral responses against post-hatch infectious laryngotracheitis virus (ILTV) infection. We first delivered the LTA into embryo day (ED)18 eggs via in ovo route so that the compound is available at the respiratory mucosa. Then the LTA treated and control ED18 eggs were allowed to hatch and the hatched chicken was infected with ILTV intratracheally on the day of hatch. We found that in ovo delivered LTA reduces ILTV infection post-hatch. We also found that in ovo delivery of LTA significantly increases mRNA expression of pro-inflammatory mediators in pre-hatch embryo lungs as well as mononuclear cell infiltration, predominantly macrophages, in lung of post-hatch chickens. Altogether, the data suggest that in ovo delivered LTA could be used to reduce ILTV infection in newly hatched chickens.

Toll-like receptor 2 ligand, lipoteichoic acid is inhibitory against infectious laryngotracheitis virus infection in vitro and in vivo.

Lipoteichoic acid (LTA) is one of the pathogen associated molecular patterns (PAMPs) that activates toll-like receptor (TLR)2-cluster of differentiation (CD)14 signalling pathway. This recognition elicits antiviral responses that have been recorded against viruses of mammals although such responses have not been characterized adequately against avian viruses. In this investigation, we characterized the LTA induced antiviral responses against infectious laryntotracheitis virus (ILTV) infection in vitro and in vivo. We found that LTA is capable of up regulating mRNA expression of innate proteins in macrophages such as MyD88, iNOS and IL-1ß and reduces the ILTV plaques in vitro. Similarly, we found that LTA treatment of embryonic day 18 (ED18) eggs can lead to the antiviral response against pre-hatch ILTV infection in vivo and is associated with expansion of macrophage populations and expression of IL-1ß and MyD88 in the lung. The data highlight that LTA can be a potential innate immune stimulant that can be used against ILTV infection in chickens.

Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer.

OBJECTIVE: The aim of this study was to investigate aortic stiffness and left ventricular (LV) systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxine (L-T4) therapy and after L-T4 withdrawal to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. METHODS: Twenty-four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24 ± 0.11 mU/L), and 4 weeks after L-T4 withdrawal (sTSH 89.82 ± 29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrand factor activity (vWF) were measured. Twenty-two healthy volunteers matched for age and sex served as euthyroid controls. RESULTS: Aortic stiffness was increased both in hypothyroidism (6.04 ± 2.88 cm(2)/dyn/10(3), p < 0.05) and subclinical hyperthyroidism (9.27 ± 4.81 cm(2)/dyn/10(3), p < 0.05) vs. controls (3.92 ± 1.84 cm(2)/dyn/10(3)). Subclinical hyperthyroidism had a more marked effect (p < 0.05). LV dimensions and ejection fractions were similar before and after L-T4 withdrawal. The E'/A' was higher in euthyroid controls (1.34 ± 1.02) as compared to both subclinical hyperthyroidism (1.0 ± 0.14, p < 0.05) and overt hypothyroidism (1.13 ± 0.98, p < 0.05). Change of aortic stiffness correlated with change of free-thyroxine (fT4), vWF and fibrinogen levels in a positive manner. CONCLUSION: Long-term thyrotropin-suppression therapy has continuous adverse effects on the arterial wall. The degree of TSH suppression in patients with DTC should be kept at the possible minimum, based on individually determined potential benefits and risks of treatment, especially in patients with cardiovascular co-morbidities.