Risk of cancer in patients with thyroid disease and venous thromboembolism

Diana H Christensen,1 Katalin Veres,1 Anne G Ording,1 Jens Otto L Jørgensen,2 Suzanne C Cannegieter,3 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands Objective: Risk of venous thromboembolism (VTE) is increased in patients with hypo/hyperthyroidism. It is unknown whether VTE may be a presenting symptom of occult cancer in these patients. Design: Nationwide population-based cohort study based on Danish medical registry data. Methods: We identified all patients diagnosed with VTE during 1978–2013 who had a previous or concurrent diagnosis of hypothyroidism (N=1481) or hyperthyroidism (N=1788). We followed them until a first-time cancer diagnosis, death, emigration, or study end, whichever came first. We calculated 1-year absolute cancer risk and standardized incidence ratios (SIRs) for cancer incidence in the study population compared with national cancer incidence in the general population. Results: During the first year after a VTE diagnosis, the 1-year absolute cancer risk was 3.0% among patients with hypothyroidism and 3.9% among those with hyperthyroidism. During the first year of follow-up, SIRs for cancer in the study population compared with the general population were 1.96 (95% CI: 1.42–2.64) among patients with hypothyroidism and 2.67 (95% CI: 2.07–3.39) among those with hyperthyroidism. SIRs declined substantially after 1 year but remained increased during the remainder of the follow-up period (up to 36 years) (SIR for hypothyroidism=1.16 [95% CI: 0.97–1.39]; SIR for hyperthyroidism=1.26 [95% CI: 1.08–1.46]). Conclusion: VTE may be a marker of underlying occult cancer in patients with hypothyroidism or hyperthyroidism. Keywords: hyperthyroidism, hypothyroidism, venous thromboembolism, cancer, cohort stud

Reliability of an injury scoring system for horses

<p>Abstract</p> <p>Background</p> <p>The risk of injuries is of major concern when keeping horses in groups and there is a need for a system to record external injuries in a standardised and simple way. The objective of this study, therefore, was to develop and validate a system for injury recording in horses and to test its reliability and feasibility under field conditions.</p> <p>Methods</p> <p>Injuries were classified into five categories according to severity. The scoring system was tested for intra- and inter-observer agreement as well as agreement with a 'golden standard' (diagnosis established by a veterinarian). The scoring was done by 43 agricultural students who classified 40 photographs presented to them twice in a random order, 10 days apart. Attribute agreement analysis was performed using Kendall's coefficient of concordance (Kendall's <it>W</it>), Kendall's correlation coefficient (Kendall's τ) and Fleiss' kappa. The system was also tested on a sample of 100 horses kept in groups where injury location was recorded as well.</p> <p>Results</p> <p>Intra-observer agreement showed Kendall's <it>W </it>ranging from 0.94 to 0.99 and 86% of observers had kappa values above 0.66 (substantial agreement). Inter-observer agreement had an overall Kendall's <it>W </it>of 0.91 and the mean kappa value was 0.59 (moderate). Agreement for all observers versus the 'golden standard' had Kendall's τ of 0.88 and the mean kappa value was 0.66 (substantial). The system was easy to use for trained persons under field conditions. Injuries of the more serious categories were not found in the field trial.</p> <p>Conclusion</p> <p>The proposed injury scoring system is easy to learn and use also for people without a veterinary education, it shows high reliability, and it is clinically useful. The injury scoring system could be a valuable tool in future clinical and epidemiological studies.</p

Impact of five years of peer-mediated interventions on sexual behavior and sexually transmitted infections among female sex workers in Mombasa, Kenya

<p>Abstract</p> <p>Background</p> <p>Since 2000, peer-mediated interventions among female sex workers (FSW) in Mombasa Kenya have promoted behavioural change through improving knowledge, attitudes and awareness of HIV serostatus, and aimed to prevent HIV and other sexually transmitted infection (STI) by facilitating early STI treatment. Impact of these interventions was evaluated among those who attended peer education and at the FSW population level.</p> <p>Methods</p> <p>A pre-intervention survey in 2000, recruited 503 FSW using snowball sampling. Thereafter, peer educators provided STI/HIV education, condoms, and facilitated HIV testing, treatment and care services. In 2005, data were collected using identical survey methods, allowing comparison with historical controls, and between FSW who had or had not received peer interventions.</p> <p>Results</p> <p>Over five years, sex work became predominately a full-time activity, with increased mean sexual partners (2.8 versus 4.9/week; <it>P </it>< 0.001). Consistent condom use with clients increased from 28.8% (145/503) to 70.4% (356/506; <it>P </it>< 0.001) as well as the likelihood of refusing clients who were unwilling to use condoms (OR = 4.9, 95%CI = 3.7–6.6). In 2005, FSW who received peer interventions (28.7%, 145/506), had more consistent condom use with clients compared with unexposed FSW (86.2% versus 64.0%; AOR = 3.6, 95%CI = 2.1–6.1). These differences were larger among FSW with greater peer-intervention exposure. HIV prevalence was 25% (17/69) in FSW attending ≥ 4 peer-education sessions, compared with 34% (25/73) in those attending 1–3 sessions (P = 0.21). Overall HIV prevalence was 30.6 (151/493) in 2000 and 33.3% (166/498) in 2005 (<it>P </it>= 0.36).</p> <p>Conclusion</p> <p>Peer-mediated interventions were associated with an increase in protected sex. Though peer-mediated interventions remain important, higher coverage is needed and more efficacious interventions to reduce overall vulnerability and risk.</p

Development of a Tetrameric Streptavidin Mutein with Reversible Biotin Binding Capability: Engineering a Mobile Loop as an Exit Door for Biotin

A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop3–4 functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop3–4 keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop7–8. This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop7–8 is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (koff of 4.28×10−4 s−1 and Kd of 1.9×10−8 M) make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible

Effect of Carbonate Chemistry Alteration on the Early Embryonic Development of the Pacific Oyster (Crassostrea gigas)

Ocean acidification, due to anthropogenic CO2 absorption by the ocean, may have profound impacts on marine biota. Calcareous organisms are expected to be particularly sensitive due to the decreasing availability of carbonate ions driven by decreasing pH levels. Recently, some studies focused on the early life stages of mollusks that are supposedly more sensitive to environmental disturbances than adult stages. Although these studies have shown decreased growth rates and increased proportions of abnormal development under low pH conditions, they did not allow attribution to pH induced changes in physiology or changes due to a decrease in aragonite saturation state. This study aims to assess the impact of several carbonate-system perturbations on the growth of Pacific oyster (Crassostrea gigas) larvae during the first 3 days of development (until shelled D-veliger larvae). Seawater with five different chemistries was obtained by separately manipulating pH, total alkalinity and aragonite saturation state (calcium addition). Results showed that the developmental success and growth rates were not directly affected by changes in pH or aragonite saturation state but were highly correlated with the availability of carbonate ions. In contrast to previous studies, both developmental success into viable D-shaped larvae and growth rates were not significantly altered as long as carbonate ion concentrations were above aragonite saturation levels, but they strongly decreased below saturation levels. These results suggest that the mechanisms used by these organisms to regulate calcification rates are not efficient enough to compensate for the low availability of carbonate ions under corrosive conditions

Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

Food Supply and Seawater pCO2 Impact Calcification and Internal Shell Dissolution in the Blue Mussel Mytilus edulis

Progressive ocean acidification due to anthropogenic CO2 emissions will alter marine ecosytem processes. Calcifying organisms might be particularly vulnerable to these alterations in the speciation of the marine carbonate system. While previous research efforts have mainly focused on external dissolution of shells in seawater under saturated with respect to calcium carbonate, the internal shell interface might be more vulnerable to acidification. In the case of the blue mussel Mytilus edulis, high body fluid pCO2 causes low pH and low carbonate concentrations in the extrapallial fluid, which is in direct contact with the inner shell surface. In order to test whether elevated seawater pCO2 impacts calcification and inner shell surface integrity we exposed Baltic M. edulis to four different seawater pCO2 (39, 142, 240, 405 Pa) and two food algae (310–350 cells mL−1 vs. 1600–2000 cells mL−1) concentrations for a period of seven weeks during winter (5°C). We found that low food algae concentrations and high pCO2 values each significantly decreased shell length growth. Internal shell surface corrosion of nacreous ( = aragonite) layers was documented via stereomicroscopy and SEM at the two highest pCO2 treatments in the high food group, while it was found in all treatments in the low food group. Both factors, food and pCO2, significantly influenced the magnitude of inner shell surface dissolution. Our findings illustrate for the first time that integrity of inner shell surfaces is tightly coupled to the animals' energy budget under conditions of CO2 stress. It is likely that under food limited conditions, energy is allocated to more vital processes (e.g. somatic mass maintenance) instead of shell conservation. It is evident from our results that mussels exert significant biological control over the structural integrity of their inner shell surfaces

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients

<p>Abstract</p> <p>Background</p> <p>About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands.</p> <p>Findings</p> <p>Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor.</p> <p>Conclusions</p> <p>Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site.</p

New Suggestions for the Mechanical Control of Bone Remodeling

Bone is constantly renewed over our lifetime through the process of bone (re)modeling. This process is important for bone to allow it to adapt to its mechanical environment and to repair damage from everyday life. Adaptation is thought to occur through the mechanosensitive response controlling the bone-forming and -resorbing cells. This report shows a way to extract quantitative information about the way remodeling is controlled using computer simulations. Bone resorption and deposition are described as two separate stochastic processes, during which a discrete bone packet is removed or deposited from the bone surface. The responses of the bone-forming and -resorbing cells to local mechanical stimuli are described by phenomenological remodeling rules. Our strategy was to test different remodeling rules and to evaluate the time evolution of the trabecular architecture in comparison to what is known from μ-CT measurements of real bone. In particular, we tested the reaction of virtual bone to standard therapeutic strategies for the prevention of bone deterioration, i.e., physical activity and medications to reduce bone resorption. Insensitivity of the bone volume fraction to reductions in bone resorption was observed in the simulations only for a remodeling rule including an activation barrier for the mechanical stimulus above which bone deposition is switched on. This is in disagreement with the commonly used rules having a so-called lazy zone