Force-deformation properties of the human heel pad during barefoot walking

Introduction: The plantar heel pad is a specialized fibroadipose tissue that attenuates and, in part, dissipates the impact energy associated with heel strike. Although near maximal deformation of the heel pad has been shown during running, in vivo measurement of the deformation and structural properties of the heel pad during walking remains largely unexplored. This study employed a fluoroscope, synchronized with a pressure platform, to obtain force–deformation data for the heel pad during walking. Methods: Dynamic lateral foot radiographs were acquired from 6 male and 10 female adults (age, 45 ± 10 yrs; height, 1.66 ± 0.10 m; and weight, 80.7 ± 10.8 kg), while walking barefoot at preferred speeds. The inferior aspect of the calcaneus was digitized and the sagittal thickness and deformation of the heel pad relative to the support surface calculated. Simultaneous measurement of the peak force beneath the heel was used to estimate the principal structural properties of the heel pad. Results: Transient loading profiles associated with walking induced rapidly changing deformation rates in the heel pad and resulted in irregular load–deformation curves. The initial stiffness (32 ± 11 N.mm-1) of the heel pad was an order of magnitude lower than its final stiffness (212 ± 125 N.mm-1) and on average, only 1.0 J of energy was dissipated by the heel pad with each step during walking. Peak deformation (10.3 mm) approached that predicted for the limit of pain tolerance (10.7 mm). Conclusion: These findings suggest the heel pad operates close to its pain threshold even at speeds encountered during barefoot walking and provides insight as to why barefoot runners may adopt ‘forefoot’ strike patterns that minimize heel loading.

Assessing rod, cone and melanopsin contributions to human pupil flicker responses

Purpose: To determine the relative contributions of rods, cones and melanopsin to pupil responses in humans using temporal sinusoidal stimulation for light levels spanning the low mesopic to photopic range. Methods: A four-primary Ganzfeld photostimulator controlled flicker stimulations at seven light levels (-2.7 to 2 log cd/m2) and five frequencies (0.5 to 8Hz). Pupil diameter was measured using a high-resolution eyetracker. Three kinds of sinusoidal photoreceptor modulations were generated using silent substitution: 1) rod modulation, 2) cone modulation, and 3) combined rod and cone modulation in phase (Experiment 1) or phase shifted (Experiment 2) from a fixed rod phase. The melanopsin excitation was computed for each condition. A vector sum model was used to estimate the relative contribution of rods, cones and melanopsin to the pupil response. Results: From Experiment 1, the pupil frequency response peaked at 1Hz at two mesopic light levels for the three modulation conditions. Analyzing the rod-cone phase difference for the combined modulations (Experiment 2) identified a V-shaped response amplitude with a minimum between 135° and 180°. The pupil response phases increased as cone modulation phase increased. The pupil amplitude increased with increasing light level for cone and combined in-phase rod and cone modulation, but not for the rod modulation. Conclusions: These results demonstrate that cone- and rod-pathway contributions are more predominant than melanopsin contribution to the phasic pupil response. The combined rod, cone and melanopsin inputs to the phasic state of the pupil light reflex follow linear summation.

GABAB receptors expressed in human aortic endothelial cells mediate intracellular calcium concentration regulation and endothelial nitric oxide synthase translocation

GABAB receptors regulate the intracellular Ca2+ concentration ([Ca2+]i) in a number of cells (e.g., retina, airway epithelium and smooth muscle), but whether they are expressed in vascular endothelial cells and similarly regulate the [Ca2+]i is not known. The purpose of this study was to investigate the expression of GABAB receptors, a subclass of receptors to the inhibitory neurotransmitter γ-aminobutyric acid (GABA), in cultured human aortic endothelial cells (HAECs), and to explore if altering receptor activation modified [Ca2+]i and endothelial nitric oxide synthase (eNOS) translocation. Real-time PCR, western blots and immunofluorescence were used to determine the expression of GABAB1 and GABAB2 in cultured HAECs. The effects of GABAB receptors on [Ca2+]i in cultured HAECs were demonstrated using fluo-3. The influence of GABAB receptors on eNOS translocation was assessed by immunocytochemistry. Both GABAB1 and GABAB2 mRNA and protein were expressed in cultured HAECs, and the GABAB1 and GABAB2 proteins were colocated in the cell membrane and cytoplasm. One hundred μM baclofen caused a transient increase of [Ca2+]i and eNOS translocation in cultured HAECs, and the effects were attenuated by pretreatment with the selective GABAB receptor antagonists CGP46381 and CGP55845. GABAB receptors are expressed in HAECs and regulate the [Ca2+]i and eNOS translocation. Cultures of HAECs may be a useful in vitro model for the study of GABAB receptors and vascular biology.

GABAB receptors are expressed in human aortic smooth muscle cells and regulate the intracellular Ca2+ concentration

The aim of this study was to investigate the expression of GABAB receptors, a subclass of receptors to the inhibitory neurotransmitter gamma-aminobutyric acid (GABAB), in human aortic smooth muscle cells (HASMCs), and to explore if altering receptor activation modified intracellular Ca(2+) concentration ([Ca(2+)]i) of HASMCs. Real-time PCR, western blots and immunofluorescence were used to determine the expression of GABABR1 and GABABR2 in cultured HASMCs. Immunohistochemistry was used to localize the two subunits in human left anterior descending artery (LAD). The effects of the GABAB receptor agonist baclofen on [Ca(2+)]i in cultured HASMCs were demonstrated using fluo-3. Both GABABR1 and GABABR2 mRNA and protein were identified in cultured HASMCs and antibody staining was also localized to smooth muscle cells of human LAD. 100 μM baclofen caused a transient increase of [Ca(2+)]i in cultured HASMCs regardless of whether Ca(2+) was added to the medium, and the effects were inhibited by pre-treatment with CGP46381 (selective GABAB receptor antagonist), pertussis toxin (a Gi/o protein inhibitor), and U73122 (a phospholipase C blocker). GABAB receptors are expressed in HASMCs and regulate the [Ca(2+)]i via a Gi/o-coupled receptor pathway and a phospholipase C activation pathway

GABAB1 and GABAB2 receptor subunits co-expressed in cultured human RPE cells regulate intracellular Ca2+ via Gi/o-protein and phospholipase C pathways

GABAB receptors associate with Gi/o-proteins that regulate voltage-gated Ca(2+) channels and thus the intracellular Ca(2+) concentration ([Ca(2+)]i), there is also reported cross-regulation of phospholipase C. These associations have been studied extensively in the brain and also shown to occur in non-neural cells (e.g. human airway smooth muscle). More recently GABAB receptors have been observed in chick retinal pigment epithelium (RPE). The aims were to investigate whether the GABAB receptor subunits, GABAB1 and GABAB2, are co-expressed in cultured human RPE cells, and then determine if the GABAB receptor similarly regulates the [Ca(2+)]i of RPE cells and if phospholipase C is involved. Human RPE cells were cultured from 5 donor eye cups. Evidence for GABAB1 and GABAB2 mRNAs and proteins in the RPE cell cultures were investigated using real time PCR, western blots and immunofluorescence. The effects of the GABAB receptor agonist baclofen, antagonist CGP46381, a Gi/o-protein inhibitor pertussis toxin, and the phospholipase C inhibitor U73122 on [Ca(2+)]i in cultured human RPE were demonstrated using Fluo-3. Both GABAB1 and GABAB2 mRNA and protein were identified in cell cultures of human RPE; antibody staining was co-localized to the cell membrane and cytoplasm. One-hundred μM baclofen caused a transient increase in the [Ca(2+)]i of RPE cells regardless of whether Ca(2+) was added to the buffer. Baclofen induced increases in the [Ca(2+)]i were attenuated by pre-treatment with CGP46381, pertussis toxin, and U73122. GABAB1 and GABAB2 are co-expressed in cell cultures of human RPE. GABAB receptors in RPE regulate the [Ca(2+)]i via a Gi/o-protein and phospholipase C pathway.

Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage

Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints. Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (137Cs γ-rays) of cells exposed to various concentrations of methylproamine. Uptake of methylproamine into cell nuclei was measured in parallel. Results: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM. Conclusions: These results are consistent with the hypothesis that radioprotection by methylproamine is mediated by attenuation of the extent of initial DNA damage.

The current state of play in human neural stem cell models : what we have learnt from the rodent

Rodent (mouse and rat) models have been crucial in developing our understanding of human neurogenesis and neural stem cell (NSC) biology. The study of neurogenesis in rodents has allowed us to begin to understand adult human neurogenesis and in particular, protocols established for isolation and in vitro propagation of rodent NSCs have successfully been applied to the expansion of human NSCs. Furthermore, rodent models have played a central role in studying NSC function in vivo and in the development of NSC transplantation strategies for cell therapy applications. Rodents and humans share many similarities in the process of neurogenesis and NSC biology however distinct species differences are important considerations for the development of more efficient human NSC therapeutic applications. Here we review the important contributions rodent studies have had to our understanding of human neurogenesis and to the development of in vitro and in vivo NSC research. Species differences will be discussed to identify key areas in need of further development for human NSC therapy applications.

Medical and nursing students perceived knowledge, attitudes, and practices concerning human immunodeficiency virus

Objective. To assess medical and nursing students’ knowledge, attitudes, and practices (KAP) regarding human immunodeficiency virus (HIV) in Fiji. Methods. A cross-sectional study of 275 medical and 252 nursing students that participated in a questionnaire survey on HIV KAP. Data was analysed according to their gender, program of study, and academic year. Results. The mean HIV knowledge (HK) and attitude scores were 16.0 and 41.3, respectively. Mean HK score was significantly higher in males compared to females. Significant positive correlations were found between HK and academic year for medical () and nursing () students and between HK and attitude scores (). The majority of students indicated fear in contracting HIV through clinical practice and felt that health care workers have the right to know a patients HIV status for their own safety. The majority would wear gloves to touch a patient if suspected of HIV. Conclusions. The study found a high level of HIV knowledge and positive attitude towards HIV patients. However, respondents also displayed negative attitudes and unacceptable practices probably due to fear. Training institutions need to ensure that students gain accurate knowledge on HIV especially on transmission routes to allay the fear of caring for HIV-infected patients.

Human resource management of Indian call centre representatives

This study examines how call centres adopt different types of human resource practices (involvement and control oriented) to manage frontline employees in Indian call centres. Data were collected from 250 call centre representatives to test the research hypotheses. The research model was analyzed using Mplus software. Findings showed that involvement and control oriented human resource practices resulted in more employee exhaustion and disengagement. Involvement oriented HRM had a positive impact on job satisfaction as well as, a positive relationship between employee exhaustion and disengagement. The findings suggest that, while involvement oriented HRM enhances job satisfaction, its implementation comes with a cost, that is, an increase in employee exhaustion and disengagement at work.

Soft tissue human thigh and buttock finite element model to simulate vehicle seat cushion indentation

Accurate modelling of automotive occupant posture 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 thigh-buttock surface shell model was based on 95th percentile male subject scan data and made of two layers, covering thin to moderate thigh and buttock proportions. To replicate the effects of skin and fat, the neoprene rubber layer was modelled as a hyperelastic material with viscoelastic behaviour. The analytical seat model is based on a Ford production seat. The result of the finite-element indentation simulation is compared to a previous simulation of an indentation with a hard shell human model of equal geometry, and to the physical indentation result. We conclude that SAE composite buttock form and human-seat indentation of a suspended seat cushion can be validly simulated.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

FGF-2 induces the proliferation of human periodontal ligament cells and modulates their osteoblastic phenotype by affecting Runx2 expression in the presence and absence of osteogenic inducers

The exact phenotype of human periodontal ligament cells (hPDLCs) remains a controversial area. Basic fibroblast growth factor (FGF‑2) exhibits various functions and its effect on hPDLCs is also controversial. Therefore, the present study examined the effect of FGF‑2 on the growth and osteoblastic phenotype of hPDLCs with or without osteogenic inducers (dexamethasone and β‑glycerophosphate). FGF‑2 was added to defined growth culture medium and osteogenic inductive culture medium. Cell proliferation, osteogenic differentiation and mineralization were measured. The selected differentiation markers, Runx2, collagen type Ⅰ, α1 (Col1a1), osteocalcin (OCN) and epidermal growth factor receptor (EGFR), were investigated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Runx2 and OCN protein expression was measured by western blotting. FGF‑2 significantly increased the proliferation of hPDLCs, but did not affect alkaline phosphatase activity. RT‑qPCR analysis revealed enhanced mRNA expression of Runx2, OCN and EGFR, but suppressed Col1a1 gene expression in the absence of osteogenic inducers, whereas all these gene levels had no clear trend in their presence. The Runx2 protein expression was clearly increased, but the OCN protein level showed no evident trend. The mineralization assay demonstrated that FGF‑2 inhibited mineralized matrix deposition with osteogenic inducers. These results suggested that FGF‑2 induces the growth of immature hPDLCs, which is a competitive inhibitor of epithelial downgrowth, and suppresses their differentiation into mineralized tissue by affecting Runx2 expression. Therefore, this may lead to the acceleration of periodontal regeneration.

Attributing human uniqueness and human nature to cultural groups : distinct forms of subtle dehumanization

Research on subtle dehumanization has focused on the attribution of human uniqueness to groups (infrahumanization), but has not examined another sense of humanness, human nature. Additionally, research has not extended far beyond Western cultures to examine the universality of these forms of dehumanization. Hence, the attribution of both forms of humanness was examined in three cross-cultural studies. Anglo-Australian and ethnic Chinese attributed values and traits (Study 1, N = 200) and emotions (Study 2, N = 151) to Australian and Chinese groups, and rated these characteristics on human uniqueness and human nature. Both studies found evidence of complementary attributions of humanness for Australians, who denied Chinese human nature but attributed them with greater human uniqueness. Chinese denied Australians human uniqueness, but their attributions of human nature varied for traits, values, and emotions. Study 3 (N = 54) demonstrated similar forms of dehumanization using an implicit method. These results and their implications for dehumanization and prejudice suggest the need to broaden investigation and theory to encompass both forms of humanness, and examine the attribution of both lesser and greater humanness to outgroups.

Balancing the books : an assessment of financial stress associated with social work and human service student placements

This report presents the findings from a study of the financial impact of work-integrated learning commonly referred to as 'placement' among social work and human services students. Based on a survey of 214 respondants, 14 in-depth interviews and two focus groups, the findings indicate that two thirds of the surveyed group felt tired and anxious about their experience of balancing paid work and placement, with 2 in 5 reporting their learning experience was compromised as a result. The significant implications and potential solutions are also discussed.