Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease.

Synaptic loss is critical in Alzheimer's disease (AD), but the dynamics of synapse turnover are poorly defined. We imaged dendritic spines in transgenic APPswe/PSen1∆E9 (APP/PS1) cerebral cortex. Dendritic spine turnover is increased far from plaque in aged APP/PS1 mice, and in young APP/PS1 mice prior to plaque formation. Dysregulation occurs in the presence of soluble Aß oligomer and requires cellular prion protein (PrPC). APP/PS1 mice lack responsiveness of spine turnover to sensory stimulation. Critically, enhanced spine turnover is coupled with the loss of persistent spines starting early and continuing with age. To evaluate mechanisms of experience-independent supranormal spine turnover, we analyzed the transcriptome of young APP/PS1 mouse brain when turnover is altered but synapse density and memory are normal, and plaque and inflammation are absent. Early PrPC-dependent expression changes occur in synaptic and lipid-metabolizing genes. Thus, pathologic synaptic dysregulation underlying AD begins at a young age prior to Aß plaque.

A Novel Method for Tracking Neck Motions Using a Skin-Conformable Wireless Accelerometer: A Pilot Study.

Introduction: Cervical spine disease is a leading cause of pain and disability. Degenerative conditions of the spine can result in neurologic compression of the cervical spinal cord or nerve roots and may be surgically treated with an anterior cervical discectomy and fusion (ACDF) in up to 137,000 people per year in the United States. A common sequelae of ACDF is reduced cervical range of motion (CROM) with patient-based complaints of stiffness and neck pain. Currently, tools for assessment of CROM are manual, subjective, and only intermittently utilized during doctor or physical therapy visits. We propose a skin-mountable acousto-mechanic sensor (ADvanced Acousto-Mechanic sensor; ADAM) as a tool for continuous neck motion monitoring in postoperative ACDF patients. We have developed and validated a machine learning neck motion classification algorithm to differentiate between eight neck motions (right/left rotation, right/left lateral bending, flexion, extension, retraction, protraction) in healthy normal subjects and patients. Methods: Sensor data from 12 healthy normal subjects and 5 patients were used to develop and validate a Convolutional Neural Network (CNN). Results: An average algorithm accuracy of 80.0 ± 3.8% was obtained for healthy normal subjects (94% for right rotation, 98% for left rotation, 65% for right lateral bending, 87% for left lateral bending, 89% for flexion, 77% for extension, 50% for retraction, 84% for protraction). An average accuracy of 67.5 ± 5.8% was obtained for patients. Discussion: ADAM, with our algorithm, may serve as a rehabilitation tool for neck motion monitoring in postoperative ACDF patients. Sensor-captured vital signs and other events (extubation, vocalization, physical therapy, walking) are potential metrics to be incorporated into our algorithm to offer more holistic monitoring of patients after cervical spine surgery.

An in vitro study into the antimicrobial and cytotoxic effect of Acticoat™ dressings supplemented with chlorhexidine.

Burn injuries can cause traumatic and debilitating physical trauma, with burn wounds prone to bacterial infection. This study examined in vitro the effectiveness of the silver nanoparticle based antimicrobial dressing, Acticoat™, in combination with a range of antimicrobial compounds against Staphylococcus aureus and Pseudomonas aeruginosa and investigated potential cytotoxic effects in multi-layered differentiated keratinocyte models. Acticoat™ with chlorhexidine was found to be highly effective against S. aureus and P. aeruginosa across a 3 day incubation period on pig skin models. MTT assays and histological staining of keratinocyte models revealed Acticoat™ had a cytotoxic effect following initial contact with the cells and cytotoxicity was exacerbated when dressings were coated with chlorhexidine and antimicrobial peptide formulations. Spectrophotometric analysis suggested that the silver nanoparticles may mobilise from the dressing as nanoclusters or silver salts, which may relate to the observed cytotoxicity. The bacterial strains used in this study showed a substantial tolerance to Acticoat™ with biofilm-like communities observed on the dressing surfaces. This could be mitigated with chlorhexidine, albeit with an increase in cytotoxicity. The clinical significance of these findings in terms of infection control and wound healing remain to be determined; the potential benefit of bactericidal activity must be balanced against cytotoxicity, and the prevalence and potential transmission of the silver tolerant phenotype must also be assessed.

Radiographic analysis of specific morphometrics and patient-reported outcomes (PROMIS) for surgical repair of zones 2 and 3 fifth metatarsal fractures.

BACKGROUND: Zones 2 and 3 fifth metatarsal fractures are often treated with intramedullary fixation due to an increased risk of nonunion. A previous 3-dimensional (3D) computerized tomography (CT) imaging study by our group determined that the screw should stop short of the bow of the metatarsal and be larger than the commonly used 4.5 millimeter (mm) screw. This study determines how these guidelines translate to operative outcomes, measured using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) surveys. Radiographic variables measuring the height of the medial longitudinal arch and degree of metatarsus adductus were also obtained to determine if these measurements had any effect on outcomes. And lastly, this study aimed to determine if morphologic differences between males and females affected surgical outcomes. METHODS: We retrospectively identified 23 patients (14 male, 9 female) who met inclusion criteria. Eighteen patients completed PROMIS surveys. Preoperative PROMIS surveys were completed prior to surgery, rather than retroactively. Weightbearing radiographs were also obtained preoperatively to assist with surgical planning and postoperatively to assess interval healing. Correlation coefficients were calculated between PROMIS scores and repair characteristics (hardware characteristics [screw length and diameter] and radiographic measurements of specific morphometric features). T tests determined the relationship between repair characteristics, PROMIS scores, and incidence of operative complications. PROMIS scores and correlation coefficients were also stratified by gender. RESULTS: The average screw length and diameter adhered to guidelines from our previous study. Preoperatively, mean PROMIS PI = 57.26±11.03 and PROMIS PF = 42.27±15.45 after injury. Postoperatively, PROMIS PI = 44.15±7.36 and PROMIS PF = 57.22±10.93. Patients with complications had significantly worse postoperative PROMIS PF scores (p=0.0151) and PROMIS PI scores (p=0.003) compared to patients without complications. Females had non-significantly worse preoperative and postoperative PROMIS scores compared to males and had a higher complication rate (33 percent versus 21 percent, respectively). Metatarsus adductus angle was shown to exhibit a significant moderate inverse relationship with postoperative PROMIS PF scores in the overall cohort (r=-0.478; p=0.045). Metatarsus adductus angle (r=-0.606; p=0.008), lateral talo-1st metatarsal angle (r=-0.592; p=0.01), and medial cuneiform height (r=-0.529; p=0.024) demonstrated significant inverse relationships with change in PROMIS PF scores for the overall cohort. Within the male subcohort, significant relationships were found between the change in PROMIS PF and metatarsus adductus angle (r=-0.7526; p=0.005), lateral talo-1st metatarsal angle (r=-0.7539; p=0.005), and medial cuneiform height (r=-0.627; p=0.029). CONCLUSION: Patients treated according to guidelines from our prior study achieved satisfactory patient reported and radiographic outcomes. Screws larger than 4.5mm did not lead to hardware complications, including screw failure, iatrogenic fractures, or cortical blowouts. Females had non-significantly lower preoperative and postoperative PROMIS scores and were more likely to suffer complications compared to males. Patients with complications, higher arched feet, or greater metatarsus adductus angles had worse functional outcomes. Future studies should better characterize whether patients with excessive lateral column loading benefit from an off-loading cavus orthotic or plantar-lateral plating.

Can procedure time for paracentesis be optimized based on bottle selection?

PURPOSE: The purpose of our study was to assess if plastic containers could decrease the overall procedure time for paracentesis relative to more commonly used glass containers. METHODS: In this IRB exempt study, initial pilot data comparing filling time of glass and plastic containers in an ex vivo setting under identical conditions revealed power calculations that n = 37 patients per group would be needed to achieve standard deviation (SD) = 60 s, difference (diff) = 40 s, two-tailed alpha-level 0.05, and power 80%. Total of 43 patients (93 containers) were enrolled and randomized to glass or plastic bottles at enrollment. Timing of bottle filling was assessed using standardized sonographic screen captures. RESULTS: An interim look at statistics at n = 20 patients indicated that original conjectures from pilot data were conservative and smaller sample size was sufficient to stop the study and conduct the analyses. Specifically, SD = 54 s, diff = 49 s, two-tailed alpha-level 0.05, and power 80% required n = 21 patients per group. Plastic containers had a statistically significantly lower average filling time per bottle (162.7 ± 53.3 s) compared to glass (212.2 ± 50.4 s) (p = 0.003). Viscosity was calculated for each specimen and did not affect the statistical significance of the results (p = 0.32). CONCLUSION: Plastic containers have 50 s time savings of per bottle filling time as compared to glass bottles as theorized based on their faster flow rate. This holds true in both an ex vivo setting and in patients and can have important downstream impacts on patient throughput, provider efficiency and system wide cost savings.

Prospective Patient Reported Outcomes (PRO) Study Assessing Outcomes of Surgically Managed Ankle Fractures.

BACKGROUND: Ankle fractures are a common cause of morbidity that have increased in incidence over the past decade. The purpose of this study was to compare the outcomes and prognosis of various fracture subtypes by using 2 validated patient-reported outcome measures: the Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) Computer Adaptive Tests (CATs). METHODS: Twelve-month postoperative PF and PI CATs were collected for 126 ankle fracture patients presenting between 2014 and 2017. Patients were stratified by ankle fracture subtype and refined by the presence/absence of concomitant deltoid injury or posterior malleolar fracture. Patients defined as members of vulnerable populations and patients presenting more than 2 weeks from time of injury or with prior acute ipsilateral fracture were excluded. The distribution of PF and PI T scores were assessed via a Shapiro-Wilk test and a 1-way analysis of variance. If significant differences were found between groups, pairwise comparisons were tested via Dwass, Steel, and Critchlow-Fligner multiple comparison analysis. RESULTS: Mean values for the PROMIS PF and PI for each fracture subtype were calculated and compared to reference population mean (SD) T scores of 50 (10): isolated lateral malleolar (PF: 50/PI: 51), isolated medial malleolar (PF: 52/PI: 49), bimalleolar (PF: 48/PI: 50), trimalleoar (PF: 47/PI: 51), isolated posterior malleolar (PF: 53/PI: 44), and isolated syndesmotic injury (PF: 60/PI: 46). Shapiro-Wilk test indicated a nonnormal distribution for the postoperative PROMIS PF T scores across all fracture patients (P = .0421). CONCLUSION: Operative fixation of an ankle fracture was able to return most patients to the population mean with regard to PROMIS function and pain regardless of fracture type. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Crack Propagation and Its Shear Mechanisms in the Bovine Descending Aorta.

Aortic dissection and rupture may involve circumferential shear stress in the circumferential-longitudinal plane. Inflation of bovine descending aortic ring specimens provides evidence of such shear from the non-uniform circumferential distortion of radial lines drawn on the circumferential-radial ring face. Delamination without tensile peeling induces cracks that propagate nearly circumferentially in the circumferential-longitudinal plane from the root of a radial cut representing rupture initiation in a ring. Translational shear deformation tests of small rectangular aortic wall blocks in the circumferential and longitudinal direction measure the consequences of such shear on substructures in the aortic wall, in particular the collagen fibers. The two directions of shear deformation produce no statistical difference in the shear stress response of the wall. Possibly, the interfiber connections between collagen fibers are put into tension by either translational shear deformation so that the stress measured reflects the tensile response of these connections. Wall rupture may involve failure of these connections; such failure is supported by the voids parallel to the collagen fibers observed in a histological study after translational shear. Further, interstitial fluid is redistributed by shear as evidenced by the measured weight loss of a set of specimens during the translational shear of blocks. Because the mass changes, mathematical modeling of aortic tissue in vitro as incompressible is an approximation. These observations suggest that no simple modification of classical rupture theories, whether based on energy functions, stress or strain, suffices to predict the rupture of hydrated soft biological tissue that has complex substructures.