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Vertical and torsional ocular misalignment can occur from mild traumatic brain injury or inner ear pathology, which may vary depending on head position. Here, we evaluate differences in a behavioral measure of binocular alignment in both upright and supine head position. Ocular perception of vertical and torsional alignment was measured using the torsional and vertical alignment nulling (TAN, VAN) task in N = 52 veterans with dizziness (N = 38 with traumatic brain injury), N = 41 civilians with vestibular schwannoma resection (UVD), and N = 33 healthy controls for both positions. The interquartile range within each group, regardless of head position, was greater for torsional compared to vertical misalignment. We use generalized estimating equations to compare average TAN (torsional) scores and VAN (vertical) scores between groups and test position. Compared to the healthy controls, TAN was significantly increased by + 0.4186° in veterans (P = 0.030) and by + 0.5747° in UVD (P = 0.010), but there was no difference with head position. For VAN, no difference was found between the three groups, but the misalignment did worsen by 0.0888° (P = 0.0070) as the head position moved from upright to supine. Head position had negligible effects on this behavioral measure of vertical and torsional binocular misalignment, and torsional misalignments were worse than controls in both veterans with dizziness and patients with vestibular nerve resection although neither reported torsional diplopia. Our data suggests that the tolerance for roll misalignment may be abnormally large in patients with dizziness. Alternatively, perceptual roll misalignments may be a manifest cause for dizziness, and therefore a useful proxy for distinguishing differences in putative otolith function in veterans with dizziness.

Background Exposure to brain injury via blast or blunt mechanisms disrupts multiple sensorimotor systems simultaneously. Large numbers of US Gulf War era and Operation Iraqi/Enduring Freedom veterans with traumatic brain injury (TBI) are suffering the symptom of dizziness - presumed due to "Multi-Sensory Impairment", a clinical pattern of damage to the auditory, visual and vestibular sensorimotor systems. Objective To describe the oculomotor response to rapid head rotation in a population of veterans with dizziness. We also describe the reliability of using the video head impulse test (vHIT) in a veteran population. Methods We used the vHIT to evaluate the vestibular-ocular reflex (VOR) gain and presence of compensatory saccades (CS) in each semicircular canal of 81 veterans (31% TBI) with dizziness. Data was collected using the ICS Otometric™ vHIT. Data was processed using both the Otometric™ software and custom software written in MATLAB™. This data was evaluated through Kruskal-Wallis rank-sum test and analysis of regression. Results Veterans with dizziness recruit CS in all semicircular canal planes even though their VOR gain is normal. The vHIT is a reliable clinical test to quantify the metrics of the VOR and CS in veterans. Conclusion Veterans with dizziness symptoms use compensatory saccades in all planes of semicircular canal rotation, despite having normal peripheral VOR gain during rapid head rotation. The video head impulse test is a stable measure of vestibular slow phase and metrics of compensatory saccades in veterans with dizziness.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are attributable to sporadic, single-gland parathyroid adenoma, in which MEN1 and CCND1/cyclin D1 are the most well-established drivers of tumorigenesis. Sporadic parathyroid carcinoma, which appears to mostly arise through molecular pathways distinct from those causing benign parathyroid tumors, is rare and is most frequently driven by mutational inactivation of the CDC73 (HRPT2) tumor suppressor gene. Targeted investigation of suspected tumor driver genes, as well as unbiased whole-genome or exome sequencing of small cohorts, have revealed additional novel candidate tumor genes in sporadic parathyroid neoplasia, generally at modest or low mutational frequencies consistent with marked molecular genetic heterogeneity from tumor to tumor. The ability of these additional candidates to participate in the pathogenic process of driving parathyroid tumorigenesis in vivo largely remains to be demonstrated experimentally. This review will summarize the molecular genetic abnormalities identified to date in sporadic PHPT and discuss the strength of evidence for their proposed roles in parathyroid tumor formation.

To explore the views of women who attended a specialist antenatal nutrition clinic that was specifically developed and piloted for pregnant women with a BMI ≥ 40 kg/mA phenomenological approach, using individual interviews, was employed. Discussions were audio recorded, transcribed verbatim and scrutinised using Interpretive Phenomenological Analysis. Themes were pinpointed and supported with direct quotes to demonstrate results.Eight women, with a BMI ≥ 40 kg/mThree main themes emerged: 1) Motivation to be Healthy; 2) Woman Centred Nutrition Care; 3) Conflicts, Confusion and Assumptions.Pregnant women with a BMI ≥ 40kgm

Objective Deficits in vestibular function increase the risk for falls while turning. However, the clinical assessment of turning in patients with vestibular dysfunction is lacking, and evidence is limited that identifies the effectiveness of vestibular physical therapy in improving turning performance. The purpose of this study was to quantify walking and turning performance during the instrumented Timed “Up & Go” (TUG) test using body-worn inertial measurement units (IMUs). Novel instrumented TUG parameters were investigated for ability to distinguish patients with unilateral vestibular deafferentation (UVD) from control groups and discriminate the differences in turning parameters of patients with UVD following vestibular physical therapy. Methods Thirty-eight individuals were recruited following UVD surgery: 26 age-matched veteran controls with reports of dizziness not from a peripheral vestibular origin, and 12 age-matched healthy controls. Participants were donned with IMUs and given verbal instructions to complete the TUG test as fast as safely possible. The IMU-instrumented and automated assessment of the TUG test provided component-based TUG parameters, including the novel walk:turn ratio. Among the participants with UVD, 19 completed an additional instrumented TUG testing after vestibular physical therapy. Results The walk:turn time ratio showed that turning performance in patients with UVD before rehabilitation is significantly more impaired than both the individuals with nonperipheral conditions and healthy controls. Vestibular rehabilitation significantly improved turning performance and “normalized” their walk:turn time ratio compared with healthy controls. The duration of the straight walking component in individuals with UVD before vestibular physical therapy, however, was not significantly different compared with that component in people after vestibular physical therapy and in healthy controls. Conclusion The IMU-instrumented TUG test can be used to distinguish individuals with vestibular deafferentation and to objectively quantify the change in their turning performance after vestibular physical therapy. Impact The IMU-based instrumented TUG parameters have the potential to quantify the efficacy of vestibular physical therapy and be adopted in the clinic.

Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases. HMMR upregulation was not required for dissemination in vivo, but enhanced ECM-mediated signaling, LUAD cell survival, and micrometastasis expansion in hyaluronan-rich microenvironments in the lung and brain metastatic niches. Our findings reveal an important mechanism by which disseminated cancer cells can coopt the inflammatory ECM to persist, leading to brain metastatic outgrowths. Cancer Res; 77(8); 1905–17. ©2017 AACR.

To examine inter-rater, intra-rater and test-re-test reliability of the Community Balance and Mobility Scale (CBM) and compare reliability in live vs videotape rating contexts for children with acquired brain injury (ABI).Repeated measures design.Seven physiotherapists (PTs) were trained as assessors. The primary assessor administered and scored baseline CBM while the second assessor observed and scored independently (inter-rater reliability). Re-assessment occurred 3-10 days later by primary assessor (test-re-test reliability). Assessments were videotaped.There were 32 participants with ABI (mean age = 14 years 1 month (SD = 2 years 1 month)). Baseline mean scores were 67.4% (18.2) and 66.7% (18.3) for primary and second assessor, respectively. Primary assessors' re-test mean score was 69.3%. Inter-rater reliability ICC was 0.93 (95% confidence interval (CI) = 0.87-0.97). Test-re-test ICC was 0.90 (95%CI = 0.81-0.95) and Bland-Altman plot indicated greatest test-re-test differences for mid-range CBM scores. Minimum detectable change (MDC₉₀) was 13.5% points.The CBM showed excellent reliability in youth. Reliability was comparable for live and videotape rating approaches, meaning that the easier and less expensive live-rating can be recommended. Future work should focus on evaluation of responsiveness to change in rehabilitation centre and community intervention contexts.

The purpose of our study was to obtain a clear understanding of the various diagnoses within the closed neural tube defect (NTD) groups included in the large database of clients in our Spina Bifida Clinic and a clear picture of the outcomes for the various NTD groups.One hundred and four clients with closed NTD were categorized using a classification system devised by Tortori-Donati et al. Various clinical markers were investigated, including ambulation and the need for orthoses and wheelchairs.Most clients are ambulatory, requiring an orthoses, but not a wheelchair, despite the high incidence of ankle/foot abnormalities.This classification system has enhanced our knowledge of this group of clients, provided a greater understanding of the varied outcomes of these children and clinical management required.

Collaborative goal setting between clinicians and clients/families is considered a fundamental component of the pediatric rehabilitation process. However, truly client-centered goal setting is not without its challenges. The purpose of this paper is to highlight theoretical concepts relevant to rehabilitation goal setting, review clinical studies directly evaluating relationships between goal setting and pediatric rehabilitation outcomes, and provide recommendations to facilitate collaborative goal processes. Four theoretical frameworks were identified that may lie behind and help explain the effectiveness of collaborative goal setting. The four relevant outcome studies found in the review revealed that individualized goal setting is an important component of the intervention, engages families more actively in therapy, and is associated to some extent with positive outcomes. The evidence suggests that the impact of fully collaborative goal setting is sufficiently positive to support investment of organizational and individual time, energy, and resources to make it an integral part of the rehabilitation process.

The membranes of healthy lymphocytes normally resist hydrolysis by secretory phospholipase A2. However, they become susceptible during the process of apoptosis. Previous experiments have demonstrated the importance of certain physical changes to the membrane during cell death such as a reduction in membrane lipid order and exposure of phosphatidylserine on the membrane surface. Nevertheless, those investigations also showed that at least one additional factor was required for rapid hydrolysis by the human group IIa phospholipase isozyme. This study was designed to test the possibility that oxidation of membrane lipids is the additional factor. Flow cytometry and confocal microscopy with a fluorescent probe of oxidative potential suggested that oxidation of the plasma membrane occurs during apoptosis stimulated by thapsigargin. When oxidative potential was high, the activity of human group IIa secretory phospholipase A2 was enhanced 30- to 100-fold compared to that observed with conditions sufficient for maximal hydrolysis by other secretory phospholipase A2 isoforms. Direct oxidation of cell membranes with either of two oxidizing agents also stimulated hydrolysis by secretory phospholipase A2. Both oxidizers caused externalization of phosphatidylserine, but a change in lipid order did not always occur. These results demonstrated that membrane oxidation strongly stimulates human group IIa secretory phospholipase A2 activity toward apoptotic cells. Interestingly, the change in membrane order, previously thought to be imperative for high rates of hydrolysis, was not required when membrane lipids were oxidized. Whether phosphatidylserine exposure is still necessary with oxidation remains unresolved since the two events could not be deconvoluted.