The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide

BACKBROUND: COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H2S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. METHODS: We examined the effect of H2S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. RESULTS: Exposure of ASM to H2S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H2S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H2S donors. Finally, we report that exogenous H2S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. CONCLUSIONS: H2S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H2S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H2S production

PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency

OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. CONCLUSIONS: This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic cause

Weddell Sea iceberg drift: Five years of observations

Since 1999, 52 icebergs have been tagged with GPS buoys in the Weddell Seato enable monitoring of their position. The chosen icebergs were of small tomedium size, with a few icebergs larger than 10 km associatedwith the calving of icebergs A38 and A43 from the Ronne Ice Shelf.The majority of icebergs were tagged off Neumayer Station (8E, 70S).It was found that smaller bergs with edges shorter than 200 m had the shortestlife cycle (< 0.5 yr). Iceberg and thus freshwater export out of theWeddell Sea was found to be highly variable. In one year the majority of buoysdeployed remained in the Weddell Sea, constituting about 40 % of the NCEP P-Efreshwater input, whereas in other years all of the tagged icebergs were exported.The observed drifts of icebergs and sea-ice showed a remarkably coherent motion.The analysis of an iceberg - sea-ice buoy array in the western Weddell Seaand an iceberg array in the eastern Weddell Sea showed a coherent sea-iceiceberg drift in sea-ice concentrations above 86 %. Dynamic kinematic parameter(DKP) during the course of coherent movement were low and deviations from the meancourse associated with the passage of low-pressure system. The length scale ofcoherent movement was estimated to be less than 250km; about half the value found forthe Arctic Ocean

Mismatch repair SNPs and thyroid cancer susceptibility: a potential role for the MSH6 rs1042821 (Gly39Glu) polymorphism

Abstract of the Poster presented at the 3rd ESPT Conference (European Society of Pharmacogenomics and Personalised Therapy / European Society of Pharmacogenomics and Theranostics), 7-9 October 2015, Budapest

Exploring the Perceived Barriers and Benefits of Physical Activity Among Wounded, Injured, and/or Sick Military Veterans

Wounded, injured, and/or sick (WIS) military veterans face significant physical and psychosocial challenges following discharge from service. Physical activity can have many positive effects on the holistic wellbeing of such individuals. However, little knowledge exists regarding the perceived barriers and benefits of physical activity within this population, creating challenges surrounding physical activity promotion. Therefore, this study was designed to identify key barriers and benefits among this population, so that informed approaches to encourage participation in physical activity can be developed. A questionnaire related to the perceived barriers and benefits of physical activity was completed by 105 WIS British military veterans. Participants were predominantly male, physically active, served in the British Army, and described their injury as frequently impacting their daily living. Factor analysis revealed that poor mental health, negative beliefs about physical activity, and low beliefs about physical capability were prominent barriers represented in the data. However, only veterans’ beliefs about their physical capability were related to physical activity levels and differed between active and insufficiently active participants. Beliefs identified as benefits of physical activity that correlated with physical activity levels were improved mental and physical health, a sense of purpose, and increased physical fitness. Subsequently, barriers and benefits were categorized using the Behaviour Change Wheel, a behavior change framework, that indicated intervention functions of education, incentivization, and persuasion might be effective methods of increasing physical activity behavior among WIS veterans. Ultimately, this will lead to greater engagement with physical activity and improved health and wellbeing within this population

A model for the compressible, viscoelastic behavior of human amnion addressing tissue variability through a single parameter

A viscoelastic, compressible model is proposed to rationalize the recently reported response of human amnion in multiaxial relaxation and creep experiments. The theory includes two viscoelastic contributions responsible for the short- and long-term time- dependent response of the material. These two contributions can be related to physical processes: water flow through the tissue and dissipative characteristics of the collagen fibers, respectively. An accurate agreement of the model with the mean tension and kinematic response of amnion in uniaxial relaxation tests was achieved. By variation of a single linear factor that accounts for the variability among tissue samples, the model provides very sound predictions not only of the uniaxial relaxation but also of the uniaxial creep and strip-biaxial relaxation behavior of individual samples. This suggests that a wide range of viscoelastic behaviors due to patient-specific variations in tissue composition

Hypogonadotropic hypogonadism due to compound heterozygous mutations TACR3 in siblings

The authors present a new association of two heterozygous TACR3 mutations (p.Arg230His and p.Trp275*) responsible for a clinical trait of normosmic congenital hypogonadotropic hypogonadism in a family.info:eu-repo/semantics/publishedVersio

Supporting genetics in primary care: investigating how theory can inform professional education

Evidence indicates that many barriers exist to the integration of genetic case finding into primary care. We conducted an exploratory study of the determinants of three specific behaviours related to using breast cancer genetics referral guidelines effectively: 'taking a family history', 'making a risk assessment', and 'making a referral decision'. We developed vignettes of primary care consultations with hypothetical patients, representing a wide range of genetic risk for which different referral decisions would be appropriate. We used the Theory of Planned Behavior to develop a survey instrument to capture data on behavioural intention and its predictors (attitude, subjective norm, and perceived behavioural control) for each of the three behaviours and mailed it to a sample of Canadian family physicians. We used correlation and regression analyses to explore the relationships between predictor and dependent variables. The response rate was 96/125 (77%). The predictor variables explained 38-83% of the variance in intention across the three behaviours. Family physicians' intentions were lower for 'making a risk assessment' (perceived as the most difficult) than for the other two behaviours. We illustrate how understanding psychological factors salient to behaviour can be used to tailor professional educational interventions; for example, considering the approach of behavioural rehearsal to improve confidence in skills (perceived behavioural control), or vicarious reinforcement as where participants are sceptical that genetics is consistent with their role (subjective norm)

Development of a planar multi-body model of the human knee joint

The aim of this work is to develop a dynamic model for the biological human knee joint. The model is formulated in the framework of multibody systems methodologies, as a system of two bodies, the femur and the tibia. For the purpose of describing the formulation, the relative motion of the tibia with respect to the femur is considered. Due to their higher stiffness compared to that of the articular cartilages, the femur and tibia are considered as rigid bodies. The femur and tibia cartilages are considered to be deformable structures with specific material characteristics. The rotation and gliding motions of the tibia relative to the femur can not be modeled with any conventional kinematic joint, but rather in terms of the action of the knee ligaments and potential contact between the bones. Based on medical imaging techniques, the femur and tibia profiles in the sagittal plane are extracted and used to define the interface geometric conditions for contact. When a contact is detected, a continuous non-linear contact force law is applied which calculates the contact forces developed at the interface as a function of the relative indentation between the two bodies. The four basic cruciate and collateral ligaments present in the knee are also taken into account in the proposed knee joint model, which are modeled as non-linear elastic springs. The forces produced in the ligaments, together with the contact forces, are introduced into the system’s equations of motion as external forces. In addition, an external force is applied on the center of mass of the tibia, in order to actuate the system mimicking a normal gait motion. Finally, numerical results obtained from computational simulations are used to address the assumptions and procedures adopted in this study.Fundação para a Ciência e a Tecnologia (FCT