A history of heart interventions moderates the relationship between psychological variables and the presence of chest pain in older women with self-reported coronary heart disease

Objectives: This study examines the hypothesis that a past history of heart interventions will moderate the relationship between psychosocial factors (stressful life events, social support, perceived stress, having a current partner, having a past diagnosis of depression or anxiety over the past 3 years, time pressure, education level, and the mental health index) and the presence of chest pain in a sample of older women. Design: Longitudinal survey over a 3-year period. Methods: The sample was taken from a prospective cohort study of 10,432 women initially aged between 70 and 75 years, who were surveyed in 1996 and then again in 1999. Two groups of women were identified: those reporting to have heart disease but no past history of heart interventions (i.e., coronary artery bypass graft/angioplasty) and those reporting to have heart disease with a past history of heart interventions. Results: Binary logistic regression analysis was used to show that for the women with self-reported coronary heart disease but without a past history of heart intervention, feelings of time pressure as well as the number of stressful life events experienced in the 12 months prior to 1996 were independent risk factors for the presence of chest pain, even after accounting for a range of traditional risk factors. In comparison, for the women with self-reported coronary heart disease who did report a past history of heart interventions, a diagnosis of depression in the previous 3 years was the significant independent risk factor for chest pain even after accounting for traditional risk factors. Conclusion: The results indicate that it is important to consider a history of heart interventions as a moderator of the associations between psychosocial variables and the frequency of chest pain in older women. Statement of Contribution: What is already known on this subject? Psychological factors have been shown to be independent predictors of a range of health outcomes in individuals with coronary heart disease, including the presence of chest pain. Most research has been conducted with men or with small samples of women; however, the evidence does suggest that these relationships exist in women as well as in men. What does this study add? Most studies have looked at overall relationships between psychological variables and health outcomes. The few studies that have looked at moderators have mainly examined gender as a moderator. To our knowledge, this is the first published study to examine a history of heart interventions as a moderator of the relationship between psychological variables and the presence of chest pain.

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

The human tissue kallikrein and kallikrein-related peptidase family

The human kallikrein-related peptidases are a subgroup of trypsin and chymotrypsin-like serine peptidases that are characterized by their homology to tissue kallikrein or kallikrein 1 (KLK1) encoded by the KLK1 gene (reviewed in[1-4]). The human KLK locus spans an approximately 320 kb region on chromosome 19q13.3-13.4 and contains fifteen genes encoding KLK1 and fourteen other kallikrein-related peptidases, KLK2-KLK15, which have been named contiguously in the locus in the order of their discovery [5-8] (Figure 606.1). It is the largest contiguous cluster of serine protease encoding genes in the human genome which has evolved from gene duplication of KLK1 and then subsequent reduplication of the newly evolved KLK genes [2]. The high conservation noted for KLK1-KLK3 (62-77%) reflects the proposed duplication of the KLK1 gene that produced the KLK2 gene which further generated the KLK3 gene. In contrast, the newer KLK4-KLK15 proteases share much less similarity, from 24-66%, although strong homology between KLK4 and KLK5, KLK9 and KLK11, and KLK10 and KLK12 suggests these genes are duplications of each other [2]...

Preparing nanocomposite fibrous scaffolds of P3HB/nHA for bone tissue engineering

Nanocomposites are recently known to be among the most successful materials in biomedical applications. In this work we sought to fabricate fibrous scaffolds which can mimic the extra cellular matrix of cartilaginous connective tissue not only to a structural extent but with a mechanical and biological analogy. Poly(3-hydroxybutyrate) (P3HB) matrices were reinforced with 5, 10 and 15 %wt hydroxyapatite (HA) nanoparticles and electrospun into nanocomposite fibrous scaffolds. Mechanical properties of each case were compared with that of a P3HB scaffold produced in the same processing condition. Spectroscopic and morphological observations were used for detecting the interaction quality between the constituents. Nanoparticles rested deep within the fibers of 1 μm in diameter. Chemical interactions of hydrogen bonds linked the constituents through the interface. Maximum elastic modulus and mechanical strength was obtained with the presence of 5%wt hydroxyapatite nanoparticles. Above 10%wt, nanoparticles tended to agglomerate and caused the entity to lose its mechanical performance; however, viscoelasticity interfered at this concentration and lead to a delayed failure. In other words, higher elongation at break and a massive work of rupture was observed at 10%wt.

The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration

Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into various cell types and have been used widely in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with the activation of the PI3K/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functinalities. Biomaterials have been modified in their properties, surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue

The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins; 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins; and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α1-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.

Prostate gland and extra-capsular tissue 3D reconstruction and measurement

Currently there are little objective parameters that can quantify the success of one form of prostate surgical removal over another. Accordingly, at Old Dominion University (ODU) we have been developing a process resulting in the use of software algorithms to assess the coverage and depth of extra-capsular soft tissue removed with the prostate by the various surgical approaches. Parameters such as the percent of capsule that is bare of soft tissue and where present the depth and extent of coverage have been assessed. First, visualization methods and tools are developed for images of prostate slices that are provided to ODU by the Pathology Department at Eastern Virginia Medical School (EVMS). The visualization tools interpolate and present 3D models of the prostates. Measurement algorithms are then applied to determine statistics about extra-capsular tissue coverage. This paper addresses the modeling, visualization, and analysis of prostate gland tissue to aid in quantifying prostate surgery success. Particular attention is directed towards the accuracy of these measurements and is addressed in the analysis discussions.

A new model to study healing of a complex femur fracture with concurrent soft tissue injury in sheep

High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed increasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.

A finite element model of seat cushion indentation with a soft tissue human occupant model

Effective digital human model (DHM) simulation of automotive driver packaging ergonomics, safety and comfort depends on accurate modelling of occupant posture, which is strongly related to the mechanical interaction between human body soft tissue and flexible seat components. This paper presents a finite-element study simulating the deflection of seat cushion foam and supportive seat structures, as well as human buttock and thigh soft tissue when seated. The three-dimensional data used for modelling thigh and buttock geometry were taken on one 95th percentile male subject, representing the bivariate percentiles of the combined hip breadth (seated) and buttock-to-knee length distributions of a selected Australian and US population. A thigh-buttock surface shell based on this data was generated for the analytic model. A 6mm neoprene layer was offset from the shell to account for the compression of body tissue expected through sitting in a seat. The thigh-buttock model is therefore made of two layers, covering thin to moderate thigh and buttock proportions, but not more fleshy sizes. To replicate the effects of skin and fat, the neoprene rubber layer was modelled as a hyperelastic material with viscoelastic behaviour in a Neo-Hookean material model. Finite element (FE) analysis was performed in ANSYS V13 WB (Canonsburg, USA). It is hypothesized that the presented FE simulation delivers a valid result, compared to a standard SAE physical test and the real phenomenon of human-seat indentation. The analytical model is based on the CAD assembly of a Ford Territory seat. The optimized seat frame, suspension and foam pad CAD data were transformed and meshed into FE models and indented by the two layer, soft surface human FE model. Converging results with the least computational effort were achieved for a bonded connection between cushion and seat base as well as cushion and suspension, no separation between neoprene and indenter shell and a frictional connection between cushion pad and neoprene. The result is compared to a previous simulation of an indentation with a hard shell human finite-element model of equal geometry, and to the physical indentation result, which is approached with very high fidelity. We conclude that (a) SAE composite buttock form indentation of a suspended seat cushion can be validly simulated in a FE model of merely similar geometry, but using a two-layer hard/soft structure. (b) Human-seat indentation of a suspended seat cushion can be validly simulated with a simplified human buttock-thigh model for a selected anthropomorphism.

Study of structural changes of pumpkin tissue before and after mechanical loading

The texture of agricultural crops changes during harvesting, post harvesting and processing stages due to different loading processes. There are different source of loading that deform agricultural crop tissues and these include impact, compression, and tension. Scanning Electron Microscope (SEM) method is a common way of analysing cellular changes of materials before and after these loading operations. This paper examines the structural changes of pumpkin peel and flesh tissues under mechanical loading. Compression and indentation tests were performed on peel and flesh samples. Samples structure were then fixed and dehydrated in order to capture the cellular changes under SEM. The results were compared with the images of normal peel and flesh tissues. The findings suggest that normal flesh tissue had bigger size cells, while the cellular arrangement of peel was smaller. Structural damage was clearly observed in tissue structure after compression and indentation. However, the damages that resulted from the flat end indenter was much more severe than that from the spherical end indenter and compression test. An integrated deformed tissue layer was observed in compressed tissue, while the indentation tests shaped a deformed area under the indenter and left the rest of the tissue unharmed. There was an obvious broken layer of cells on the walls of the hole after the flat end indentations, whereas the spherical indenter created a squashed layer all around the hole. Furthermore, the influence of loading was lower on peel samples in comparison with the flesh samples. The experiments have shown that the rate of damage on tissue under constant rate of loading is highly dependent on the shape of equipment. This fact and observed structural changes after loading underline the significance of deigning post harvesting equipments to reduce the rate of damage on agricultural crop tissues.

Extremely cold and hot temperatures increase the risk of ischaemic heart disease mortality : epidemiological evidence from China

Objective: To examine the effects of extremely cold and hot temperatures on ischaemic heart disease (IHD) mortality in five cities (Beijing, Tianjin, Shanghai, Wuhan and Guangzhou) in China; and to examine the time relationships between cold and hot temperatures and IHD mortality for each city. Design: A negative binomial regression model combined with a distributed lag non-linear model was used to examine city-specific temperature effects on IHD mortality up to 20 lag days. A meta-analysis was used to pool the cold effects and hot effects across the five cities. Patients: 16 559 IHD deaths were monitored by a sentinel surveillance system in five cities during 2004–2008. Results: The relationships between temperature and IHD mortality were non-linear in all five cities. The minimum-mortality temperatures in northern cities were lower than in southern cities. In Beijing, Tianjin and Guangzhou, the effects of extremely cold temperatures were delayed, while Shanghai and Wuhan had immediate cold effects. The effects of extremely hot temperatures appeared immediately in all the cities except Wuhan. Meta-analysis showed that IHD mortality increased 48% at the 1st percentile of temperature (extremely cold temperature) compared with the 10th percentile, while IHD mortality increased 18% at the 99th percentile of temperature (extremely hot temperature) compared with the 90th percentile. Conclusions: Results indicate that both extremely cold and hot temperatures increase IHD mortality in China. Each city has its characteristics of heat effects on IHD mortality. The policy for response to climate change should consider local climate–IHD mortality relationships.

Chaotic soul - messy heart : the phenomenon of experiencing auditory hallucinations

Globally, it is estimated that 24 million people live with schizophrenia (WHO, 2008), while 1.2 million people have been diagnosed with schizophrenia in Indonesia. Auditory hallucinations are a key symptom of schizophrenia according to the DSM IV-TR (Frances, First, & Pincus, 2002). It is estimated that the prevalence of auditory hallucinations in people with schizophrenia range from 64.3% to 83.4% (Thomas et al., 2007). Until recently, the majority of studies were conducted in Western societies the primary focus of which, has been on the causes and treatments of auditory hallucinations (Walton, 1999) and on the biological and cognitive aspects of the phenomenon (Changas, Garcia-Montes, de Lemus & Olivencia, 2003). While a few studies have explored the lived experience of people with schizophrenia, there is little research about the experience of auditory hallucinations. Therefore, the focus of this study was on an exploration of the experience of auditory hallucinations as described by Indonesian people living with schizophrenia. Based on the available literature, there have been no published qualitative studies relating to the lived experience of auditory hallucinations as described by Indonesian people diagnosed with schizophrenia. Husserlian descriptive phenomenological approach was applied in explicating the phenomenon of auditory hallucinations in this study. In-depth audio-taped interviews were conducted with 13 participants. Analysis of participant transcripts was undertaken using Colaizzi.s (1973) approach. Eight major themes were explicated: Feeling more like a robot than a human being - feeling compelled to respond to auditory hallucinations; voices of contradiction - a point of confusion; a frightening experience, the voices emerged at times of loss and grief; disruption to daily living; tattered relationships and family disarray; finding a personal path to living with auditory hallucinations; seeking relief in Allah through prayer and ritual. Experiencing auditory hallucinations for people diagnosed with schizophrenia is a journey of challenges as each individual struggles to understand their now changed life-world, reconstruct a sense of meaning within their illness experience, and to carve out a pathway to wellness. The challenge for practitioners is to learn from those who have experienced auditory hallucinations, to be with them in their journey of recovery and wellness, and to apply a person-centered approach to care within the context of a multidisciplinary team.

Mathematical modelling of tumour growth and interaction with host tissue and the immune system

In this thesis, three mathematical models describing the growth of solid tumour incorporating the host tissue and the immune system response are developed and investigated. The initial model describes the dynamics of the growing tumour and immune response before being extended in the second model by introducing a time-varying dendritic cell-based treatment strategy. Finally, in the third model, we present a mathematical model of a growing tumour using a hybrid cellular automata. These models can provide information to pre-experimental work to assist in designing more effective and efficient laboratory experiments related to tumour growth and interactions with the immune system and immunotherapy.