From pelvic radiation to social isolation: a qualitative study of survivors' experiences of chronic bowel symptoms after pelvic radiotherapy.

PURPOSE: We explored survivors' experiences of chronic bowel symptoms following pelvic radiotherapy, strategies employed in living with these symptoms, effects on daily activities, and roles at home and in the workplace. METHODS: Semi-structured interviews were conducted with 28 individuals (10 gynaecological, 14 prostate, four anal/rectal cancer survivors) who had completed pelvic radiotherapy at least six months prior to data collection and who had experience of bowel symptoms during this post-treatment period. Reflexive thematic analysis was undertaken. RESULTS: We propose four themes describing a process leading from experience of symptoms to withdrawal from activities and roles. These are (1) losing control (the experience of unintended anal leakage or discharge); (2) experiencing embarrassment and fear (the experience of embarrassment or fear of embarrassment as a result of discharge becoming public); (3) managing and reacting (acting to reduce the likelihood of discharge or to prevent this becoming public); and (4) restriction and withdrawal (avoiding specific activities or situations so as to reduce or remove the risk of embarrassment). Returning to the workplace presented additional challenges across these themes. CONCLUSIONS: Impacts of chronic bowel symptoms can be severe. Survivors employ a variety of methods and strategies in living with their symptoms. Some of these support continued role fulfilment but some constitute a withdrawal from pre-treatment roles. Current healthcare provision and statutory protections fail to fully meet needs following pelvic radiotherapy. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to develop and implement evidence-based services and supported self-management programmes for survivors experiencing chronic bowel problems post-radiotherapy.

Modeling and control of anterior-posterior and medial-lateral sways in standing posture.

To study essential anterior-posterior and medial-lateral sways of the stance caused by rotational movements about the ankle and hip joints, a mathematical model is developed for the 3D postural kinematics and dynamics. The model is in the form of nonlinear differential-algebraic equations corresponding to a biomechanical system with holonomic constraints. A nonlinear feedback control law is further derived for stabilizing the upright stance, whilst eliminating internal torques induced by the constraints on postural movements. Numerical simulations of the model parametrized with experimental data of human body segments illustrate the performance of postural balancing with the proposed control.

"It's just inappropriate": Harassment of dental students by patients.

INTRODUCTION: Harassment is an issue that occurs in all workplaces and institutions. Due to increased exposure to patients, higher rates of harassment are experienced in health care systems. Health care workers need to form a professional relationship with patients to attend to their health care needs; however, harassment by patients can disrupt this relationship and have detrimental physical, mental, and emotional impacts on the health practitioner. OBJECTIVE: The purpose of this study was to examine the prevalence and impact of harassment by patients toward clinical students at a prominent Australasian dental school. METHODS: A 14-item survey was distributed to clinical students. The survey collected basic demographic information and contained Likert-scale closed questions on harassment prevalence and experience and a free text question asking for details of a significant harassment experience. Descriptive statistics and analysis of free text data were performed. RESULTS: The response rate was 67%. About 20% of respondents reported experiencing at least one incident of harassment. Verbal harassment was most commonly reported, followed by sexual and racial harassment. All incidences of sexual harassment were reported by female students, while racial harassment was most frequently reported by students of Asian ethnicity. Most students indicated they were unsure of how to respond to harassment by patients. CONCLUSION: Dental students were exposed to harassment by patients. IMPLICATIONS: Appropriate policies and education on responding to harassment, alongside support for the same, could help ensure the safety and wellbeing of students.

The mechanical loading and muscle activation of four common exercises used in osteoporosis prevention for early postmenopausal women.

High impact exercise can reduce postmenopausal bone loss, however stimulus frequency (loading cycles per second) can affect osteogenesis. We aimed to examine the effect of stimulus frequency on the mechanical loading of four common osteoporosis prevention exercises, measuring body acceleration and muscle activation with accelerometry and electromyography (EMG), respectively. Fourteen early postmenopausal women completed randomised countermovement jumps (CMJ), box-drops (BD), heel-drops (HD) and stamp (STP) exercises for continuous and intermittent stimulus frequencies. Sacrum accelerometry and surface electromyography (EMG) of four muscles were recorded. CMJ (mean ±â€¯SD: 10.7 ±â€¯4.8 g & 10.0 ±â€¯5.0 g), BD (9.6 ±â€¯4.1 g & 9.5 ±â€¯4.0 g) and HD (7.3 ±â€¯3.8 g & 8.6 ±â€¯4.4 g) conditions generated greater peak acceleration than STP (3.5 ±â€¯1.4 g & 3.6 ±â€¯1.7 g) across continuous and intermittent trials. CMJ and BD generated greater acceleration gradients than STP across continuous and intermittent trials. CMJ generated greater rectus femoris EMG than all other exercises, CMJ and BD generated greater semitendinosus and tibialis anterior EMG than HD across continuous and intermittent trials. CMJ and BD provide greater peak acceleration than STP and remain similar during different stimulus frequencies. CMJ, BD and HD may exceed STP in maintaining postmenopausal bone health.

New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction.

OBJECTIVES: Legg-Calvé-Perthes' disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. METHODS: Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. RESULTS: The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. CONCLUSION: The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease.Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148-156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1.

The role of social context in symptom appraisal and help-seeking among people with lung or colorectal symptoms: A qualitative interview study.

Prolonged diagnostic intervals are associated with poorer outcomes, and the patient interval appears to be a substantial contributor to the overall length of the diagnostic interval. This study sought to understand how the broader context of people's lives influenced symptom appraisal and help-seeking, comparing experiences by length of the patient interval. Patients referred with a suspicion of lung or colorectal cancer were invited to complete a questionnaire about their symptoms, with 26 respondents purposively sampled to take part in a semi-structured interview about their patient intervals. Embodied experience, appraisal, help-seeking decision-making and consultation were identified as component stages of the patient interval, with the factors affecting movement between these stages located in one of four contextual domains: individual experience, interpersonal relationships, healthcare system interactions and social and temporal context. The length of the patient interval was related to the type of symptom(s) experienced, discussion of symptoms with others and the social responsibilities people held during symptomatic periods. A contextual model of the patient interval illustrates the stages and domains of this interval, as grounded in the data from this study. The model has potential application to future studies examining the patient interval for a range of symptoms.

Structural Characteristics of α-Synuclein Oligomers.

Oligomeric forms of amyloid aggregates have been detected in the brains and tissues of patients suffering from neurodegenerative disorders such as Parkinson's disease, and it is widely thought that such species are key pathogenic agents in the development and spreading of the disease; however, the study of these species has been proven to be extremely challenging, primarily as a result of their intrinsically transient nature and high levels of heterogeneity. Identifying the structural nature and the details of the mechanisms of formation and interconversion of individual oligomeric species, particularly those with high toxicity, is of fundamental importance not only for understanding the mechanisms of protein misfolding and amyloid aggregation but also for the identification of diagnostic and therapeutic targets. In this review, we will focus on the current knowledge of the multitude of oligomeric forms of α-synuclein that have been reported to date, with particular emphasis on their structural features and possible relationship to other amyloid species, in order to build a clearer understanding of the types of oligomeric species that accumulate during the aggregation of α-synuclein and to develop a comprehensive picture of the misfolding behavior of the protein.

Tibial impacts and muscle activation during walking, jogging and running when performed overground, and on motorised and non-motorised treadmills.

PURPOSE: To examine tibial acceleration and muscle activation during overground (OG), motorised treadmill (MT) and non-motorised treadmill conditions (NMT) when walking, jogging and running at matched velocities. METHODS: An accelerometer recorded acceleration at the mid-tibia and surface EMG electrodes recorded rectus femoris (RF), semitendinosus (ST), tibialis anterior (TA) and soleus (SL) muscle activation during OG, MT and NMT locomotion whilst walking, jogging and running. RESULTS: The NMT produced large reductions in tibial acceleration when compared with OG and MT conditions across walking, jogging and running conditions. RF EMG was small-moderately higher in the NMT condition when compared with the OG and MT conditions across walking, jogging and running conditions. ST EMG showed large and very large increases in the NMT when compared to OG and MT conditions during walking whilst SL EMG found large increases on the NMT when compared to OG and MT conditions during running. The NMT condition generated very large increases in step frequency when compared to OG and MT conditions during walking, with large and very large decreases during jogging and very large decreases during running. CONCLUSIONS: The NMT generates large reductions in tibial acceleration, moderate to very large increases in muscular activation and large to very large decreases in cycle time when compared to OG and MT locomotion. Whilst this may decrease the osteogenic potential of NMT locomotion, there may be uses for NMTs during rehabilitation for lower limb injuries.

Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study.

BACKGROUND: This prospective cohort study aimed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis. METHODS: Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions; we also examined primary care and hospital records for diagnostic routes and diagnoses. Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage. RESULTS: Among 963 participants, 15.9% were diagnosed with primary lung cancer, 5.9% with other thoracic malignancies and 78.2% with non-malignant conditions. Only half the cohort had an isolated first symptom (475, 49.3%); synchronous first symptoms were common. Haemoptysis, reported by 21.6% of cases, was the only initial symptom associated with cancer. Diagnostic intervals were shorter for cancer than non-cancer diagnoses (91 vs 124 days, P=0.037) and for late-stage than early-stage cancer (106 vs 168 days, P=0.02). Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses (P=0.003). CONCLUSIONS: Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients. Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution.

Spatial propagation of protein polymerization.

We consider the spatial dependence of filamentous protein self-assembly. Through studying the cases where the spreading of aggregated material is dominated either by diffusion or by growth, we derive analytical results for the spatial evolution of filamentous protein aggregation, which we validate against Monte Carlo simulations. Moreover, we compare the predictions of our theory with experimental measurements of two systems for which we identify the propagation as either growth or diffusion controlled. Our results connect the macroscopic observables that characterize the spatial propagation of protein self-assembly with the underlying microscopic processes and provide physical limits on spatial propagation and prionlike behavior associated with protein aggregation.

Chaperone proteins select and maintain [PIN+] prion conformations in Saccharomyces cerevisiae.

Prions are proteins that can adopt different infectious conformations known as "strains" or "variants," each with a distinct, epigenetically inheritable phenotype. Mechanisms by which prion variants are determined remain unclear. Here we use the Saccharomyces cerevisiae prion Rnq1p/[PIN(+)] as a model to investigate the effects of chaperone proteins upon prion variant determination. We show that deletion of specific chaperone genes alters [PIN(+)] variant phenotypes, including [PSI(+)] induction efficiency, Rnq1p aggregate morphology/size and variant dominance. Mating assays demonstrate that gene deletion-induced phenotypic changes are stably inherited in a non-Mendelian manner even after restoration of the deleted gene, confirming that they are due to a bona fide change in the [PIN(+)] variant. Together, our results demonstrate a role for chaperones in regulating the prion variant complement of a cell.

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

BACKGROUND: Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. OBJECTIVES AND METHODS: This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. RESULTS: Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased ß-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CONCLUSION: CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

Validation of a morphometric reconstruction technique applied to a juvenile pelvis.

Three-dimensional reconstructions of bone geometry from microCT (computed tomography) data are frequently used in biomechanical and finite element analyses. Digitization of bone models is usually a simple process for specimens with a complete geometry, but in instances of damage or disarticulation it can be very challenging. Subsequent to digitization, further imaging techniques are often required to estimate the geometry of missing bone or connecting cartilage. This paper presents an innovative approach to the reconstruction of incomplete scan data, to reproduce proper anatomical arrangements of bones, including absent connecting cartilaginous elements. Utilizing geometric morphometric tools, the reconstruction technique is validated through comparison of a reconstructed 9 year old pelvis, to the original CT data. A principal component analysis and an overlay of the two pelves provide a measure of the accuracy of the reconstructed model. Future work aims to investigate the biomechanical effects of any minor positional error on the bone's predicted structural properties through the use of finite element analysis.

Amyloidogenicity and aggregate cytotoxicity of human glucagon-like peptide-1 (hGLP-1).

The potential of human glucagon-like peptide-1 (hGLP-1) as a therapeutic agent is limited by its high aggregation propensity. We show that hGLP-1 forms amyloid-like structures that are preceded by cytotoxic aggregates, suggesting that aggregation of biopharmaceuticals could present a cytotoxic risk to patients besides the reported increased risk in immunogenicity.

Chemical form of dietary L-carnitine affects plasma but not tissue carnitine concentrations in male Sprague-Dawley rats.

In Experiment 1, rats (n = 54) were randomly assigned to control or one of the four sources of l-Carnitine supplemented at either 100 or 200 micromol/kg/day and were allowed to acclimate for 14 days. Following a 12-h fast, plasma samples were obtained at 0, 5, 10, 15, 30, 60, 120, 240, 480 and 720 min after l-Carnitine feeding and assayed for free l-Carnitine concentration. Plasma-free l-Carnitine levels were affected by time after treatment intake (p < 0.0001) and l-Carnitine source (p < 0.0001). The time x source interaction was not statistically significant (p = 0.99). In Experiment 2, rats (n = 54) were randomly assigned to control or one of the four sources of l-Carnitine at either 100 or 200 micromol/kg/day and were acclimated as in experiment 1. Rats were sacrificed 120 min after feeding. Samples of liver and skeletal muscle were obtained and assayed for free l-Carnitine concentration. Neither skeletal muscle (p = 0.44) or liver (p = 0.59) tissue concentrations of l-Carnitine were affected by any l-Carnitine source as compared with the control. We conclude that some differences exist in plasma concentrations of free l-Carnitine following ingestion of different chemical forms of l-Carnitine. It is unclear if these differences in the circulating concentration of free l-Carnitine translate into any physiological differences for the animal. In this study, chemical form of l-Carnitine had no effect on skeletal muscle or liver tissue concentrations of l-Carnitine in young male Wistar rats.

Reclassification of Pediococcus dextrinicus (Coster and White 1964) back 1978 (Approved Lists 1980) as Lactobacillus dextrinicus comb. nov., and emended description of the genus Lactobacillus.

The taxonomic status of Pediococcus dextrinicus is described and transfer of the species to the genus Lactobacillus, with the name Lactobacillus dextrinicus comb. nov., is proposed. This reclassification is supported by multilocus sequence analysis of the 16S rRNA gene and Cpn60, PheS, RecA and RpoA proteins. The mode of cell division and existing phenotypic information also show that P. dextrinicus does not belong to the genus Pediococcus, but rather to the genus Lactobacillus. As such, we propose that Pediococcus dextrinicus is reclassified as Lactobacillus dextrinicus comb. nov. (type strain ATCC 33087(T)=DSM 20335(T)=JCM 5887(T)=LMG 11485(T)=NCDO 1561(T)).

Sleeping beauty mutase (sbm) is expressed and interacts with ygfd in Escherichia coli.

In Escherichia coli, a four-gene operon, sbm-ygfD-ygfG-ygfH, has been shown to encode a putative cobalamin-dependent pathway with the ability to produce propionate from succinate in vitro [Haller T, Buckel T, Retey J, Gerlt JA. Discovering new enzymes and metabolic pathways: conversion of succinate to propionate by Escherichia coli. Biochemistry 2000;39:4622-4629]. However, the operon was thought to be silent in vivo, illustrated by the eponym describing its first gene, "sleeping beauty mutase" (methylmalonyl-CoA mutase, MCM). Of the four genes described, only ygfD could not be assigned a function. In this study, we have evaluated the functional integrity of YgfD and Sbm and show that, indeed, both proteins are expressed in E. coli and that YgfD has GTPase activity. We show that YgfD and Sbm can be co-immunoprecipitated from E. coli extracts using antibody to either protein, demonstrating in vivo interaction, a result confirmed using a strain deleted for ygfD. We show further that, in vitro, purified His-tagged YgfD and Sbm behave as a monomer and dimer, respectively, and that they form a multi-subunit complex that is dependent on pre-incubation of YgfD with non-hydrolysable GTP, an outcome that was not affected by the state of Sbm, as holo- or apoenzyme. These studies reinforce a role for the in vivo interaction of YgfD and Sbm.

Masticatory loading and bone adaptation in the supraorbital torus of developing macaques.

Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply.