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Article ; Online: NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury

Frances Corrigan / Ibolja Cernak / Kelly McAteer / Sarah C. Hellewell / Jeffrey V. Rosenfeld / Renée J. Turner / Robert Vink

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 9

Abstract: Abstract Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by ... ...

Abstract	Abstract Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by the accumulation of hyperphosphorylated tau protein, with the resultant tau tangles thought to initiate the cognitive and behavioral manifestations that appear as the condition progresses. However, the mechanisms linking concussive and blast TBI with tau hyperphosphorylation are unknown. Here we show that single moderate TBI, repeated concussive TBI and blast-induced mild TBI all result in hyperphosphorylation of tau via a substance P mediated mechanism. Post-injury administration of a substance P, NK1 receptor antagonist attenuated the injury-induced phosphorylation of tau by modulating the activity of several key kinases including Akt, ERK1/2 and JNK, and was associated with improvement in neurological outcome. We also demonstrate that inhibition of the TRPV1 mechanoreceptor, which is linked to substance P release, attenuated injury-associated tau hyperphosphorylation, but only when it was administered prior to injury. Our results demonstrate that TBI-mediated stimulation of brain mechanoreceptors is associated with substance P release and consequent tau hyperphosphorylation, with administration of an NK1 receptor antagonist attenuating tau phosphorylation and associated neurological deficits. NK1 antagonists may thus represent a pharmacological approach to attenuate the potential development of CTE following concussive and blast TBI.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Advanced 3D printed model of middle cerebral artery aneurysms for neurosurgery simulation

Ruth G. Nagassa / Paul G. McMenamin / Justin W. Adams / Michelle R. Quayle / Jeffrey V. Rosenfeld

3D Printing in Medicine, Vol 5, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract Background Neurosurgical residents are finding it more difficult to obtain experience as the primary operator in aneurysm surgery. The present study aimed to replicate patient-derived cranial anatomy, pathology and human tissue properties ... ...

Abstract	Abstract Background Neurosurgical residents are finding it more difficult to obtain experience as the primary operator in aneurysm surgery. The present study aimed to replicate patient-derived cranial anatomy, pathology and human tissue properties relevant to cerebral aneurysm intervention through 3D printing and 3D print-driven casting techniques. The final simulator was designed to provide accurate simulation of a human head with a middle cerebral artery (MCA) aneurysm. Methods This study utilized living human and cadaver-derived medical imaging data including CT angiography and MRI scans. Computer-aided design (CAD) models and pre-existing computational 3D models were also incorporated in the development of the simulator. The design was based on including anatomical components vital to the surgery of MCA aneurysms while focusing on reproducibility, adaptability and functionality of the simulator. Various methods of 3D printing were utilized for the direct development of anatomical replicas and moulds for casting components that optimized the bio-mimicry and mechanical properties of human tissues. Synthetic materials including various types of silicone and ballistics gelatin were cast in these moulds. A novel technique utilizing water-soluble wax and silicone was used to establish hollow patient-derived cerebrovascular models. Results A patient-derived 3D aneurysm model was constructed for a MCA aneurysm. Multiple cerebral aneurysm models, patient-derived and CAD, were replicated as hollow high-fidelity models. The final assembled simulator integrated six anatomical components relevant to the treatment of cerebral aneurysms of the Circle of Willis in the left cerebral hemisphere. These included models of the cerebral vasculature, cranial nerves, brain, meninges, skull and skin. The cerebral circulation was modeled through the patient-derived vasculature within the brain model. Linear and volumetric measurements of specific physical modular components were repeated, averaged and compared to the original 3D meshes generated from the medical imaging data. Calculation of the concordance correlation coefficient (ρc: 90.2%–99.0%) and percentage difference (≤0.4%) confirmed the accuracy of the models. Conclusions A multi-disciplinary approach involving 3D printing and casting techniques was used to successfully construct a multi-component cerebral aneurysm surgery simulator. Further study is planned to demonstrate the educational value of the proposed simulator for neurosurgery residents.
Keywords	Neurosurgical training ; Anatomical models ; Aneurysm ; 3D printing ; Simulation ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	670
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI

Jerome J. Maller / Thomas Welton / Matthew Middione / Fraser M. Callaghan / Jeffrey V. Rosenfeld / Stuart M. Grieve

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 13

Abstract: Abstract The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion ... ...

Abstract	Abstract The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion MRI in both a single 1150-direction dataset and a large normal cohort (n = 94; 391-directions). Using a connectomic approach, we identified six dominant pathways in terms of strength, length and anatomy, and characterised them by their age and gender variation. The strongest individual connection was to the ipsilateral thalamus. There was a strong age dependence of hippocampal connectivity to medial occipital regions. Overall, our results concur with preclinical and ex-vivo data, confirming that meaningful in vivo characterisation of hippocampal connections is possible in an individual. Our findings extend the collective knowledge of hippocampal anatomy, highlighting the importance of the spinal-limbic pathway and the striking lack of hippocampal connectivity with motor and sensory cortices.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is antibiotic treatment effective in the management of chronic low back pain with disc herniation? Study protocol for a randomised controlled trial

Donna M. Urquhart / Jeffrey V. Rosenfeld / Maurits van Tulder / Anita E. Wluka / Karin Leder / Allen C. Cheng / Andrew B. Forbes / Patrick Chan / Richard O’Sullivan / Susan Liew / Flavia M. Cicuttini

Trials, Vol 22, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract Background There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc ... ...

Abstract	Abstract Background There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. Methods One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. Discussion There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015
Keywords	Antibiotics ; Low back pain ; Disc herniation ; Modic change ; Randomised controlled trial ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Measuring the effectiveness of in-hospital and on-base Prevent Alcohol and Risk-related Trauma in Youth (P.A.R.T.Y.) programs on reducing alcohol related harms in naval trainees

Jason Watterson / Belinda Gabbe / Paul Dietze / Jennifer Thompson / Michael Oborn / Jeffrey V. Rosenfeld

BMC Public Health, Vol 17, Iss 1, Pp 1-

P.A.R.T.Y. Defence study protocol

2017 Volume 6

Abstract: Abstract Background Reducing alcohol related harms in Australian Defence Force (ADF) trainees has been identified as a priority, but there are few evidence-based prevention programs available for the military setting. The study aims to test whether the P. ...

Abstract	Abstract Background Reducing alcohol related harms in Australian Defence Force (ADF) trainees has been identified as a priority, but there are few evidence-based prevention programs available for the military setting. The study aims to test whether the P.A.R.T.Y. program delivered in-hospital or on-base, can reduce harmful alcohol consumption among ADF trainees. Methods/design The study is a 3-arm randomized controlled trial, involving 953 Royal Australian Navy trainees from a single base. Trainees, aged 18 to 30 years, will be randomly assigned to the study arms: i. in-hospital P.A.R.T.Y.; ii. On-base P.A.R.T.Y.; and iii. Control group. All groups will receive the routine ADF annual alcohol awareness training. The primary outcome is the proportion of participants reporting an Alcohol Use Disorders Identification Test (AUDIT) score of 8 or above at 12 months’ post-intervention. The secondary outcome is the number of alcohol related incidents reported to the Royal Australian Navy (RAN) in the 12 months’ post-intervention. Discussion This is the first trial of the use of the P.A.R.T.Y. program in the military. If the proposed intervention proves efficacious, it may be a useful program in the early education of RAN trainees. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001332617 , date of registration: 18/12/2014 ‘retrospectively registered’.
Keywords	Military personnel ; Awareness ; Risk-taking ; Alcohol ; Public aspects of medicine ; RA1-1270
Subject code	796
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease

David Oehme / Tony Goldschlager / Peter Ghosh / Jeffrey V. Rosenfeld / Graham Jenkin

Stem Cells International, Vol

A Systematic Review of Animal Studies and Human Clinical Trials

2015 Volume 2015

Keywords	Medicine ; R ; Internal medicine ; RC31-1245
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease

David Oehme / Tony Goldschlager / Peter Ghosh / Jeffrey V. Rosenfeld / Graham Jenkin

Stem Cells International, Vol

A Systematic Review of Animal Studies and Human Clinical Trials

2015 Volume 2015

Abstract: Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc ... ...

Abstract	Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.
Keywords	Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Rifat Latifi / Kee B Park / Haitham Shoman / Lubna Samad / Luke Caddell / Patricia Garcia / Tariq Khan / Leonidas Quintana / Sergio Aguilera / Roxanna Garcia / Robert Dempsey / Jeffrey V Rosenfeld / Corey Scurlock / Nigel Crisp / Montray Smith / Laura Lippa / Rashid Jooma / Russell J Andrews

BMJ Global Health, Vol 5, Iss

Who are the real community health workers in Tshopo Province, Democratic Republic of the Congo?

2020 Volume 1

Keywords	Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Global health, global surgery and mass casualties

BMJ Global Health, Vol 5, Iss

II. Mass casualty centre resources, equipment and implementation

2020 Volume 1

Abstract: Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when ... ...

Abstract	Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when combined with the trauma/stroke centre concept. Mass casualty centres (MCCs) integrate resources for both routine and emergency care—from prevention to acute care to rehabilitation. Integration of the various healthcare systems—governmental, non-governmental and military—is key to avoid both duplication and gaps. With input from LMIC and HIC personnel of various backgrounds—trauma and subspecialty surgery, nursing, information technology and telemedicine, and healthcare administration—creative solutions to the challenges of expanding care (both daily and disaster) are developed. MCCs are evolving initially in Chile and Pakistan. Technologies for cost-effective healthcare in LMICs include smartphone apps (enhance prehospital care) to electronic data collection and analysis (quality improvement) to telemedicine and drones/robots (support of remote regions and resource optimisation during both daily care and disasters) to resilient, mobile medical/surgical facilities (eg, battery-operated CT scanners). The co-ordination of personnel (within LMICs, and between LMICs and HICs) and the integration of cost-effective advanced technology are features of MCCs. Providing quality, cost-effective care 24/7/365 to the 5 billion who lack it presently makes MCCs an appealing means to achieve the healthcare-related United Nations Sustainable Development Goals for 2030.
Keywords	Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
Subject code	360
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of a targeted, theory-informed implementation intervention designed to increase uptake of emergency management recommendations regarding adult patients with mild traumatic brain injury

Marije Bosch / Joanne E. McKenzie / Jennie L. Ponsford / Simon Turner / Marisa Chau / Emma J. Tavender / Jonathan C. Knott / Russell L. Gruen / Jill J. Francis / Sue E. Brennan / Andrew Pearce / Denise A. O’Connor / Duncan Mortimer / Jeremy M. Grimshaw / Jeffrey V. Rosenfeld / Susanne Meares / Tracy Smyth / Susan Michie / Sally E. Green

Implementation Science, Vol 14, Iss 1, Pp 1-

results of the NET cluster randomised trial

2019 Volume 16

Abstract: Abstract Background Evidence-based guidelines for management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available; however, clinical practice remains inconsistent with these guidelines. A targeted, theory- ... ...

Abstract	Abstract Background Evidence-based guidelines for management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available; however, clinical practice remains inconsistent with these guidelines. A targeted, theory-informed implementation intervention (Neurotrauma Evidence Translation (NET) intervention) was designed to increase the uptake of three clinical practice recommendations regarding the management of patients who present to Australian EDs with mild head injuries. The intervention involved local stakeholder meetings, identification and training of nursing and medical local opinion leaders, train-the-trainer workshops and standardised education materials and interactive workshops delivered by the opinion leaders to others within their EDs during a 3 month period. This paper reports on the effects of this intervention. Methods EDs (clusters) were allocated to receive either access to a clinical practice guideline (control) or the implementation intervention, using minimisation, a method that allocates clusters to groups using an algorithm to minimise differences in predefined factors between the groups. We measured clinical practice outcomes at the patient level using chart audit. The primary outcome was appropriate screening for post-traumatic amnesia (PTA) using a validated tool until a perfect score was achieved (indicating absence of acute cognitive impairment) before the patient was discharged home. Secondary outcomes included appropriate CT scanning and the provision of written patient information upon discharge. Patient health outcomes (anxiety, primary outcome: Hospital Anxiety and Depression Scale) were also assessed using follow-up telephone interviews. Outcomes were assessed by independent auditors and interviewers, blinded to group allocation. Results Fourteen EDs were allocated to the intervention and 17 to the control condition; 1943 patients were included in the chart audit. At 2 months follow-up, patients attending intervention EDs (n = 893) compared with ...
Keywords	Mild traumatic brain injury ; Cluster trial ; Effectiveness ; Emergency department ; Implementation science ; Clinical practice guideline ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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