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Circumcision does not alter long-term glucocorticoids accumulation or psychological effects associated with trauma- and stressor-related disorders
Get PDFThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease. This procedure has frequently been criticized by various communities claiming that circumcision in infancy and early adolescence were psychologically traumatizing with medical implications up into old age. Due to the lack of evidence concerning an alleged increase in vulnerability, we measured objective and subjective stress and trauma markers, including glucocorticoids from hair samples, in circumcised and non-circumcised males. We found no differences in long-term limbic–hypothalamic–pituitary–adrenal axis activity, subjective stress perception, anxiety, depressiveness, physical complaints, sense of coherence and resilience. Rather, an increase in the glucocorticoid levels indicated a healthy lifestyle and appropriate functioning. Thus, our findings provide evidence that male circumcision does not promote psychological trauma. Moreover, a qualitative approach, the ambivalence construct, was used for the discussion, aiming at a discourse devoid of biases
Insulin in motion: The A6-A11 disulfide bond allosterically modulates structural transitions required for insulin activity
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The structural transitions required for insulin to activate its receptor and initiate regulation of glucose homeostasis are only partly understood. Here, using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers (cis and trans). Remarkably, only the cis isomer displays full insulin potency, rapidly lowering blood glucose in mice (even under insulin-resistant conditions). It also posseses reduced mitogenic activity in vitro. Further biophysical, crystallographic and molecular-dynamics analyses reveal that the A6-A11 bond configuration directly affects the conformational flexibility of insulin A-chain N-terminal helix, dictating insulin’s ability to engage its receptor. We reveal that in native insulin, contraction of the Cα-Cα distance of the flexible A6-A11 cystine allows the A-chain N-terminal helix to unwind to a conformation that allows receptor engagement. This motion is also permitted in the cis isomer, with its shorter Cα-Cα distance, but prevented in the extended trans analogue. These findings thus illuminate for the first time the allosteric role of the A6-A11 bond in mediating the transition of the hormone to an active conformation, significantly advancing our understanding of insulin action and opening up new avenues for the design of improved therapeutic analogues
Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals
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© 2017 John Wiley & Sons, Inc. All rights reserved.
This author accepted manuscript is made available following 12 month embargo from date of publication (May 2017) in accordance with the publisher’s archiving policyBackground
Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals.
Methods
High resolution manometry (HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5‐point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale (HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns.
Key Results
One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry (HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception (R2 up to .70).
Conclusion and Inferences
Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility
Glutathione monoethyl ester prevents TDP-43 pathology in motor neuronal NSC-34 cells
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (August 2017) in accordance with the publisher’s archiving policyOxidative stress is recognised as central in a range of neurological diseases including Amyotrophic lateral sclerosis (ALS), a disease characterised by fast progressing death of motor neurons in the brain and spinal cord. Cellular pathology includes cytosolic protein aggregates in motor neurons and glia of which potentially cytotoxic hyper-phosphorylated fragments of the Transactive response DNA Binding Protein 43 kDa (TDP-43) constitute a major component. This is closely associated with an additional loss of nuclear TDP-43 expression indicating a “loss of function” mechanism, accelerating motor neuron (MN) loss. Furthermore, mutations in TDP-43 cause familial ALS and ALS-like disease in animal models. In this study, we investigated the role of glutathione (GSH) in modulating oxidative stress responses in TDP-43 pathology in motor neuron NSC-34 cells. Results demonstrate that depletion of GSH produces pathology similar to that of mutant TDP-43, including occurrence of cytosolic aggregates, TDP-43 phosphorylation and nuclear clearing of endogenous TDP-43. We also demonstrate that introduction of mutant TDP-43A315T and silencing of endogenous TDP-43, but not overexpression of wild-type TDP-43, result in similar pathology, including depletion of intracellular GSH, possibly resulting from a decreased expression of a regulatory subunit of ɣ-glutamylcysteine ligase (GCLM), a rate limiting enzyme in GSH synthesis. Importantly, treatment of mutant cells with GSH monoethyl ester (GSHe) that directly increases intracellular GSH and bypasses the need for GSH synthesis, protected against mutant-induced TDP-43 pathology, including reducing aggregate formation, nuclear clearance, reactive oxygen species (ROS) production and cell death. Our data strongly suggest that oxidative stress is central to TDP-43 pathology and may result from a loss of function affecting GSH synthesis and that treatments directly aimed at restoring cellular GSH content may be beneficial in preventing cell death in TDP-43-mediated ALS
Traumatic subaxial cervical facet subluxation and dislocation: epidemiology, radiographic analyses, and risk factors for spinal cord injury
Get PDF© 2017 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyBackground Context
Distractive flexion injuries (DFIs) of the subaxial cervical spine are major contributors to spinal cord injury (SCI). Prompt assessment and early intervention of DFIs associated with SCI are crucial to optimize patient outcome; however, neurologic examination of patients with subaxial cervical injury is often difficult, as patients commonly present with reduced levels of consciousness. Therefore, it is important to establish potential associations between injury epidemiology and radiographic features, and neurologic involvement.
Purpose
The aims of this study were to describe the epidemiology and radiographic features of DFIs presenting to a major Australian tertiary hospital and to identify those factors predictive of SCI. The agreement and repeatability of radiographic measures of DFI severity were also investigated.
Study Design/Setting
This is a combined retrospective case-control and reliability-agreement study.
Patient Sample
Two hundred twenty-six patients (median age 40 years [interquartile range = 34]; 72.1% male) who presented with a DFI of the subaxial cervical spine between 2003 and 2013 were reviewed.
Outcome Measures
The epidemiology and radiographic features of DFI, and risk factors for SCI were identified. Inter- and intraobserver agreement of radiographic measurements was evaluated.
Methods
Medical records, radiographs, and computed tomography and magnetic resonance imaging scans were examined, and the presence of SCI was evaluated. Radiographic images were analyzed by two consultant spinal surgeons, and the degree of vertebral translation, facet apposition, spinal canal occlusion, and spinal cord compression were documented. Multivariable logistic regression models identified epidemiology and radiographic features predictive of SCI. Intraclass correlation coefficients (ICCs) examined inter- and intraobserver agreement of radiographic measurements.
Results
The majority of patients (56.2%) sustained a unilateral (51.2%) or a bilateral facet (48.8%) dislocation. The C6–C7 vertebral level was most commonly involved (38.5%). Younger adults were over-represented among motor-vehicle accidents, whereas falls contributed to a majority of DFIs sustained by older adults. Greater vertebral translation, together with lower facet apposition, distinguished facet dislocation from subluxation. Dislocation, bilateral facet injury, reduced Glasgow Coma Scale, spinal canal occlusion, and spinal cord compression were predictive of neurologic deficit. Radiographic measurements demonstrated at least a “moderate” agreement (ICC>0.4), with most demonstrating an “almost perfect” reproducibility.
Conclusions
This large-scale cohort investigation of DFIs in the cervical spine describes radiographic features that distinguish facet dislocation from subluxation, and associates highly reproducible anatomical and clinical indices to the occurrence of concomitant SCI
Daughters and their mothers: The reproduction of pronatalist discourses across generations
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This author accepted manuscript is made available following 24 month embargo from date of publication (March 2017) in accordance with the publisher’s archiving policyThe expectation that all women will become mothers, and that they will mother in particular ways, has been a focus of feminist attention for many decades. What has been less considered is how pronatalist discourses are reproduced across generations within the same family. This article draws on interviews with five pairs of white middle class daughters currently planning to have children and their mothers living in South Australia, in order to examine the ways in which mother-daughter relationships are a key site for the reproduction of pronatalist discourses. Three recurring themes are examined: 1) expectations mothers have of their daughters to have children, 2) (grand)mothers as advice-givers, and 3) generational differences relating to paid work combined with the continued privileging of mothering. The article concludes with a discussion of the ways in which pronatalist discourses are mobilised in mother-daughter relationships, and how these position women in relation to motherhood.This work was supported by the Australian Research Council under a Future Fellowship, FT130100087
A preliminary investigation on the effect of extracorporeal shock wave therapy as a treatment for neurogenic heterotopic ossification following traumatic brain injury. Part I: Effects on pain
Get PDF“This is an Accepted Manuscript of an article published by Taylor & Francis in Brain Injury on 24 March 2017, available online: http://www.tandfonline.com/10.1080/02699052.2017.1283059.”Copyright © 2017 Taylor & Francis Group, LLC
This author manuscript is made available following 12 month embargo from date of publication (24 March 2017) in accordance with publisher’s copyright policyIntroduction: Neurogenic heterotopic ossification (NHO) is a complication of a neurological injury following traumatic brain injury (TBI) and may be present around major synovial joints. It is often accompanied by severe pain, which may lead to limitation in activities of daily living. Currently, a common intervention for NHO is surgery, which has been reported to carry many additional risks. This study was designed to assess the effect of extracorporeal shock wave therapy (ESWT) on pain in patients with TBI with chronic NHO.
Methods: A series of single-case studies (n = 11) was undertaken with patients who had TBI and chronic NHO at the hip or knee. Each patient received four applications of high-energy EWST delivered to the affected joint over 8 weeks. Two-weekly follow-up assessments were carried out, and final assessments were made 3 and 6 months post-intervention. Pain was measured using the Faces Rating Scale, and X-rays were taken at baseline and 6-months post-intervention to physiologically measure the size of the NHO.
Results: The application of high-energy ESWT was associated with significant overall reduction of pain in patients with TBI and NHO (Tau-0.412, 95% confidence interval −0.672 to −0.159, p = 0.002).
Conclusions: ESWT is a novel non-invasive intervention for reducing pain resulting from NHO in patients with TBI
Meta-analysis of optical lowcoherence reflectometry versus partial coherence interferometry biometry
No full textThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/A meta-analysis to compare ocular biometry measured by optical low-coherence reflectometry (Lenstar LS900; Haag Streit) and partial coherence interferometry (the IOLMaster optical biometer; Carl Zeiss Meditec). A systematic literature search was conducted for articles published up to August 6th 2015 in the Cochrane Library, PubMed, Medline, Embase, China Knowledge Resource Integrated Database and Wanfang Data. A total of 18 studies involving 1921 eyes were included. There were no statistically significant differences in axial length (mean difference [MD] 0 mm; 95% confidence interval (CI) −0.08 to 0.08 mm; p = 0.92), anterior chamber depth (MD 0.02 mm; 95% CI −0.07 to 0.10 mm; p = 0.67), flat keratometry (MD −0.05 D; 95% CI −0.16 to 0.06 D; p = 0.39), steep keratometry (MD −0.09 D; 95% CI −0.20 to 0.03 D; p = 0.13), and mean keratometry (MD −0.15 D; 95% CI −0.30 to 0.00 D; p = 0.05). The white to white distance showed a statistically significant difference (MD −0.14 mm; 95% CI −0.25 to −0.02 mm; p = 0.02). In conclusion, there was no difference in the comparison of AL, ACD and keratometry readings between the Lenstar and IOLMaster. However the WTW distance indicated a statistically significant difference between the two devices. Apart from the WTW distance, measurements for AL, ACD and keratometry readings may be used interchangeability with both devices
Exploring the Potential of Anticipated Regret as an Emotional Cue to Improve Bowel Cancer Screening Uptake
No full textCopyright © 2017 Ian T. Zajac et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Objective. Bowel cancer is currently the second leading cause of cancer-related death in Australia and screening participation is suboptimal. This study examined the role of emotion in the form of anticipated regret (AR) and its relationship to screening intentions.
Methods. N=173 persons aged 45 to 80 years completed a survey measuring demographic variables, readiness to screen, relative importance of health by comparison to other life priorities, satisfaction with current health, and AR if not participating in future bowel cancer screening.
Results. AR was a significant predictor of future screening intentions. Those with higher levels of AR were seven times more likely (OR = 7.18) to intend to screen in the future compared to those with lower AR. This relationship was not compromised when controlling for other variables including gender and satisfaction with one’s health. AR levels were significantly lower in people who had been screened previously and in those with full health insurance.
Conclusions. These results demonstrate that AR is uniquely related to future bowel cancer screening intentions. Future studies should continue to consider this as a useful target for behavioural interventions and identify new ways of delivering these interventions to improve their reach
GAMBLINGLESS: FOR LIFE study protocol: a pragmatic randomised trial of an online cognitive–behavioural programme for disordered gambling
No full textThis is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0