A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Background

Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition.

Methods

We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood–brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively.

Results

Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood–brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury.

Conclusions

The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.     

Living donor program crisis management plans: Current landscape and talking point recommendations

Although minimized by expert evaluation, operative technique, and postoperative care, the extremely low risk of perioperative mortality following living kidney or liver donation will never be eliminated. Furthermore, anticipation of poor donor outcome may simultaneously be a source of anxiety for physicians and programs and also be a circumstance for which they are unprepared. We conducted a national survey of US transplant surgeons to understand experiences with and systemic preparedness for the event of a living donor death. Respondents represented 87 unique transplant programs (71 kidney and 16 liver donor programs). Perioperative deaths were rare, as expected. Although most respondents (N = 57, 64% of total respondents; 88% of liver programs) reported being moderately to extremely concerned about a future living donor death at their institution, only 30 (33% of total program respondents) had a written plan available in the case of such an event; 63% of programs would find guidance and recommendations useful. To help address this gap, the American Society of Transplantation Live Donor Community of Practice (AST LDCOP) developed Living Donor Crisis Management Plan Talking Points suitable to guide crisis plan development at transplant programs.     

Quality indicators in colonoscopy: an evolving paradigm

The year 1969 marked a revolution in the diagnosis of colorectal cancer (CRC). It is when Dr Wolff developed the colonoscope and quickly realized its potential in both diagnosis and treatment of colonic neoplasms. Over the past 50 years there has been exponential increase in utilization of colonoscopy with over 1 million colonoscopies performed annually throughout Australasia. Endoscopic removal of pre‐malignant lesions has been proven to reduce the incidence and mortality of colorectal. Although timing and frequency of surveillance colonoscopy plays a crucial role in risk reduction of CRC, this is dependent upon the findings of the index colonoscopy. The goal of screening colonoscopy is to detect CRC and identify and remove pre‐malignant neoplasms that risk progression to CRC. With increasing uptake of bowel screening throughout Australasia, there is increasing pressure to ensure all endoscopists and endoscopy units perform at a universal high‐quality. All too often high demand and constant delays compromise colonoscopy quality. Without clear and concise quality indicators with transparent measurement and audit, these flaws can quickly jeopardize screening goals and patient outcomes. This review aims to explore six key quality indicators and explore the evidence behind the current recommended standards. These key indicators include; rate of adequate bowel preparation, caecal intubation rate, adenoma detection rate, withdrawal time, complication rates and surveillance intervals.     

Does the cement stiffness affect fatigue fracture strength of vertebrae after cement augmentation in osteoporotic patients?

Purpose

Normal progression of osteoporosis or the rigid reinforcement of the fractured vertebral body with polymethyl methacrylate (PMMA) cement is being discussed as a cause for adjacent-level fractures after vertebroplasty. The purpose of this study was to investigate whether augmentation with low stiffness cement can decrease the risk of adjacent-level fractures in low-quality bone.

Methods

Eighteen female osteoporotic lumbar specimens (L1–L5) were harvested and divided into three groups according to bone mineral density: (I) native; (II) PMMA; (III) modified PMMA (lower stiffness). For the PMMA and modified PMMA groups, a compression fracture was first mechanically induced in L3, and then the fracture received vertebroplasty treatment. The cement stiffness reduction of the modified PMMA group was achieved via an addition of 8 mL of serum to the typical PMMA base. All specimens were exposed to cyclic loading (4 Hz) and a stepwise increasing applied peak force. Cement stiffness was tested according to ISO 5833.

Results

A 51 % decrease in cement stiffness was achieved in the modified PMMA group (954 ± 141 vs. 1,937 ± 478 MPa, p < 0.001). Fatigue fracture force (the force level during cyclic loading at which the deformation experienced a sudden increase; FFF) was significantly affected by bone quality (r ² = 0.39, p = 0.006) and by the initial fracture force (the force necessary to create the initial fracture in L3 prior to augmentation; r ² = 0.82, p < 0.001). Using initial fracture force as a covariate, the FFF of the modified PMMA group (1,764 ± 49 N) was significantly higher than in the PMMA group (1,544 ± 55 N; p = 0.03).

Conclusions

A possible method to reduce adjacent-level fractures after vertebroplasty in patients with reduced bone quality could be the use of a lower modulus cement. Therefore, mixing cement with biocompatible fluids could prove useful to tailor cement properties in the operating theater.     

The association between fecal incontinence and sexual activity and function in women attending a tertiary referral center

Introduction and hypothesis

To determine whether fecal incontinence (FI) is associated with sexual activity and to compare sexual function in women with and without FI.

Methods

We conducted a retrospective chart review of all new patients seen in an academic urogynecology clinic. Women who reported fecal incontinence, as defined by loss of fecal material on the Wexner scale, were compared with those without fecal incontinence. We compared sexual activity and Pelvic Organ Prolapse Incontinence Sexual Questionnaire-12 (PISQ-12) scores between groups.

Results

In our population of women with pelvic floor disorder, 588 women reported FI compared with 527 who did not. On multivariate analysis, FI was not associated with sexual activity status, but was associated with worsened PISQ-12 scores (p?<?0.001). PISQ-12 item analysis found that women with FI reported more dyspareunia, fear, and avoidance of sexual activity with greater partner problems (all p <0.05) than women without FI.

Conclusions

Women with FI were as likely to engage in sexual relations as women without FI; however, sexually active women with FI had poorer sexual function than those without FI.     

Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro

Schwann cells, the myelin-forming cells of the PNS, are attractive candidates for remyelination therapy as they can remyelinate CNS axons. Yet their integration in CNS tissue appears hampered, at least in part, by their limited motility in the CNS environment. As the polysialylated (PSA) form of NCAM regulates migration of neural precursors in the CNS and is not expressed by developing Schwann cells, we investigated whether conferring sustained expression of PSA to Schwann cells derived from postnatal rats enhances their motility. Cells were transduced with a retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on NCAM. Migration of wild type and transduced cells expressing STX or the marker gene alkaline phosphatase was examined using a gap bridging assay in dissociated cells and by grafting cells in slice cultures of postnatal brain. Migration of PSA expressing cells was significantly increased in both models, as compared to control cells, and this effect was abolished by endoneuraminidase-N stripping of PSA. PSA-positive Schwann cells retained the ability to differentiate in vitro and expressed the Krox20 and P zero myelination markers. When grafted in neonatal cerebellar slices, STX-transduced cells started to myelinate Purkinje cell axons like control cells and make myelin internodes after 2 to 3 weeks. PSA was redistributed on the cell membrane and downregulated during differentiation in pure Schwann cell cultures and slice co-cultures. Thus, migratory properties of PNS myelin-forming cells within the CNS can be enhanced without altering their differentiation program. This finding may be beneficial for the development of remyelination therapies.     

Dyslexia and across-hands finger localization deficits

Two experiments on finger localization are reported. Experiment 1 compared children who were poor readers with two groups of children matched to poor readers for sex and either age (CA controls) or reading age (RA controls). The participant's hands were kept out of his or her sight in a semi-open box while the fingers of one hand were lightly touched by the experimenter. The participant's task was to indicate, using the thumb of either the same hand (within-hand condition) or the opposite hand (across-hands condition) to respond, the finger(s) which had been touched by the experimenter. Performance was significantly impaired in the across-hands condition compared with the within-hand condition. Experiment 2 was carried out with dyslexic adults and a control group of normal readers. Using the same method of responding as in Experiment 1, a significant deficit in the across-hands condition compared to the within-hand condition was found for both groups. The effect was also obtained for both groups when participants were required to point to the relevant fingers on a photograph of a hand rather than use the thumb of the opposite hand to respond. The results are discussed in relation to the hypothesis of a deficit in inter-hemispheric transfer of tactile information in dyslexia.