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The purpose of this study is to assess the impact of a germicidal ultraviolet light-emitting diode (LED) on the contamination level of a back table in the operating room (OR) during total joint arthroplasty procedures.Eight Tryptic Soy Agar petri plates were placed on a table located near the operative field and exposed to air. One plate was removed on the hour over an 8-hour time span. The back table had either an UV-LED for disinfection or a sham UV-LED. This process was repeated in 12 different ORs (6 with UV light, 6 with sham device). The plates were then incubated for 48 hours at 36°C ± 1°C . Colony forming units (CFU) were recorded 24 and 48 hours after incubation.There was a statistically significant difference in total CFUs between the intervention vs sham at 24-hours (27 vs 95, P = .0001) and 48-hours (38 vs 122, P.0001). The multivariate analysis revealed that the 24-hour and 48-hour count, the predictors UV light (P = .002) and hour of plate removal (P = .050) were statistically significantly associated with CFU counts. Together, the predictor variables explained 15.8% and 23.0% of the variance in CFU counts at 24- and 48-hours, respectively.A back table UV-LED may decrease environmental contamination near the operative field. This has potential to lead to a decrease in joint infection.

The role of molecular chaperones, such as heat shock protein 70 (Hsp70), is not typically studied as a function of biological sex, but by addressing this gap we might improve our understanding of proteinopathic disorders that predominate in one sex. Therefore, we exposed male or female primary hippocampal cultures to preformed α-synuclein fibrils in a model of early-stage Lewy pathology. We first discovered that two mechanistically distinct inhibitors of Hsp70 function increased phospho-α-synuclein(+) inclusions more robustly in male-derived neurons. Because Hsp70 is released into extracellular compartments and may restrict cell-to-cell transmission/amplification of α-synucleinopathy, we then tested the effects of low-endotoxin, exogenous Hsp70 (eHsp70) in primary hippocampal cultures. eHsp70 was taken up by and reduced α-synuclein(+) inclusions in cells of both sexes, but pharmacological suppression of Hsp70 function attenuated the inhibitory effect of eHsp70 on perinuclear inclusions only in male neurons. In 20-month-old male mice infused with α-synuclein fibrils in the olfactory bulb, daily intranasal eHsp70 delivery also reduced inclusion numbers and the time to locate buried food. eHsp70 penetrated the limbic system and spinal cord of male mice within 3 h but was cleared within 72 h. Unexpectedly, no evidence of eHsp70 uptake from nose into brain was observed in females. A trend towards higher expression of inducible Hsp70—but not constitutive Hsp70 or Hsp40—was observed in amygdala tissues from male subjects with Lewy body disorders compared to unaffected male controls, supporting the importance of this chaperone in human disease. Women expressed higher amygdalar Hsp70 levels compared to men, regardless of disease status. Together, these data provide a new link between biological sex and a key chaperone that orchestrates proteostasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01114-6.

Postoperative urinary retention (POUR) after total knee arthroplasty (TKA) may cause urologic injury and delay patient discharge. This study measures the incidence of POUR and identifies predictive risk factors.Two-hundred seventy-one consecutive patients undergoing primary unilateral TKA were prospectively enrolled. Bladder scans were performed in the postanesthesia care unit (PACU) and every four hours thereafter. POUR was defined as400cc with inability to void and was treated with catheterization. Patient demographics, urologic history, operative data, perioperative medications, and bladder scanner volumes were investigated with the univariate and multivariate logistic regression analysis.Fifty-five patients (20%) developed POUR. Compared with non-POUR patients, PACU bladder scan volumes were greater in patients who developed POUR (344cc vs 120cc, P.001). POUR patients had lower BMI (27.8 vs 29.4, P = .03), longer operative duration (83.9 vs 76.0 minutes, P = .002), and lower ASA scores (2.2 vs 2.4, P = .02). Total intravenous fluid was equivalent between groups (1134cc vs 1185cc, P = .41). POUR patients received less narcotics measured by morphine milligram equivalents (16.1 vs 23.9, P.001). Fifteen variables including spinal type (bupivacaine and ropivacaine) and paralytic use were not predictive of POUR. Potentially predictive variables included anesthetic types administered (spinal, general, regional, and combination) and perioperative administration of nonsteroidal anti-inflammatory drugs (NSAIDs), glycopyrrolate, and muscle relaxants. The multivariate analysis showed that NSAIDs (P = .05) and glycopyrrolate (P = .04) were significant predictors.A significant percentage of patients develop POUR after TKA. Select patient demographics and PACU bladder scanning may identify those at risk. Appropriate pain control and judicious use of perioperative NSAIDs and glycopyrrolate may help minimize the risk of POUR.

Lewy body disorders are characterized by oxidative damage to DNA and inclusions rich in aggregated forms of α-synuclein. Among other roles, apurinic/apyrimidinic endonuclease 1 (APE1) repairs oxidative DNA damage, and APE1 polymorphisms have been linked to cases of Lewy body disorders. However, the link between APE1 and α-synuclein is unexplored. We report that knockdown or inhibition of APE1 amplified inclusion formation in primary hippocampal cultures challenged with preformed α-synuclein fibrils. Fibril infusions into the mouse olfactory bulb/anterior olfactory nucleus (OB/AON) elicited a modest decrease in APE1 expression in the brains of male mice but an increase in females. Similarly, men with Lewy body disorders displayed lower APE1 expression in the OB and amygdala compared to women. Preformed fibril infusions of the mouse OB/AON induced more robust base excision repair of DNA lesions in females than males. No fibril-mediated loss of APE1 expression was observed in male mice when the antioxidant N-acetylcysteine was added to their diet. These findings reveal a potential sex-biased link between α-synucleinopathy and APE1 in mice and humans. Further studies are warranted to determine how this multifunctional protein modifies α-synuclein inclusions and, conversely, how α-synucleinopathy and biological sex interact to modify APE1.

At early disease stages, Lewy body disorders are characterized by limbic vs. brainstem α-synucleinopathy, but most preclinical studies have focused solely on the nigrostriatal pathway. Furthermore, male gender and advanced age are two major risk factors for this family of conditions, but their influence on the topographical extents of α-synucleinopathy and the degree of cell loss are uncertain. To fill these gaps, we infused α-synuclein fibrils in the olfactory bulb/anterior olfactory nucleus complex-one of the earliest and most frequently affected brain regions in Lewy body disorders-in 3-month-old female and male mice and in 11-month-old male mice. After 6 months, we observed that α-synucleinopathy did not expand significantly beyond the limbic connectome in the 9-month-old male and female mice or in the 17-month-old male mice. However, the 9-month-old male mice had developed greater α-synucleinopathy, smell impairment and cell loss than age-matched females. By 10.5 months post-infusion, fibril treatment hastened mortality in the 21.5-month-old males, but the inclusions remained centered in the limbic system in the survivors. Although fibril infusions reduced the number of cells expressing tyrosine hydroxylase in the substantia nigra of young males at 6 months post-infusion, this was not attributable to true cell death. Furthermore, mesencephalic α-synucleinopathy, if present, was centered in mesolimbic circuits (ventral tegmental area/accumbens) rather than within strict boundaries of the nigral pars compacta, which were defined here by tyrosine hydroxylase immunolabel. Nonprimate models cannot be expected to faithfully recapitulate human Lewy body disorders, but our murine model seems reasonably suited to (i) capture some aspects of Stage IIb of Lewy body disorders, which displays a heavier limbic than brainstem component compared to incipient Parkinson's disease; and (ii) leverage sex differences and the acceleration of mortality following induction of olfactory α-synucleinopathy.

A Cu-azolate metal–organic framework (MOF) uptakes stoichiometric loadings of Groups 1 and 2 metal halides, demonstrating efficient reversible release and reincorporation of immobilized anions within the framework. Ion-pairing interactions lead to anion-dependent Li+ and Mg2+ transport in Cu4(ttpm)2·0.6CuCl2, whose high surface area affords a high density of uniformly distributed mobile metal cations and halide binding sites. The ability to systematically tune the ionic conductivity yields a solid electrolyte with a Mg2+ ion conductivity rivaling the best materials reported to date. This MOF is one of the first in a promising class of frameworks that introduces the opportunity to control the identity, geometry, and distribution of the cation hopping sites, offering a versatile template for application-directed design of solid electrolytes.

Introduction Obesity (body mass index [BMI] ≥30 kg/m^2) in men is associated with low testosterone (T) levels, and the prevalence of testosterone deficiency (TD) is greater in obese men. Information is limited regarding how BMI affects the pharmacokinetic (PK) profile or dosing of testosterone therapies (TTh) in men with TD. Serum total testosterone (TT) trough concentration (C-trough)-guided dosing achieved physiological serum TT levels (300-1100 ng/dL) in a Phase 3 trial of subcutaneous (SC) testosterone enanthate (TE) administered weekly. Objective This post-hoc analysis evaluated the association between BMI and serum TT to assess PK parameters of weekly SC TE treatment in men with TD and varying BMIs. Methods Concentration-controlled SC TE was evaluated in a single-arm Phase 3 trial. The primary endpoint was the percentage of patients who received ≥1 dose of SC TE (Safety Population) achieving an average serum TT concentration of 300-1100 ng/dL over the 7-day dosing interval, C-avg (0-168h), at Week 12. The PK Population (n=142) included all patients in the Safety Population with ≥1 blood sample drawn post-dose. Patients in the PK Population who completed the study through Week 12 (n=137) were categorized into tertiles based on baseline BMI: Tertile 1 (BMI ≤29 kg/m^2; n=45), Tertile 2 (BMI >29-32 kg/m^2; n=33), and Tertile 3 (BMI >32 kg/m^2; n=59). Assessed PK parameters included C-trough, AUC-(0-168h), C-avg (0-168h), and C-max. Weeks 6 and 12 C-trough and C-avg (0-168h) were assessed by BMI tertiles. C-trough and C-avg (0-168h) were calculated according to their Week 12 treatment doses, and an overall dose-normalized linear regression model at Week 12 was used. Results At baseline, mean (SD) serum TT levels for patients in Tertiles 1-3 were 250.7 (101.3), 235.3 (91.2), and 226.4 (81.1) ng/dL, respectively. Prior to dosing adjustments at Week 6, Tertiles 2 and 3 mean (SD) C-trough (459.2 [157.0] and 453.2 [133.0] ng/dL) were lower than Tertile 1 (616.9 [181.6] ng/dL). At Week 6, 21.2% of the total variance in C-trough levels could be predicted from BMI (P Conclusions Week 12 TT C-trough, C-avg (0-168h), and C-max were inversely related to BMI, suggesting an important role for BMI and final dose selection in SC TE exposure. Patients with higher BMI tertiles may require higher testosterone dosing to replete physiologic levels. Disclosure Yes, this is sponsored by industry/sponsor: Antares Pharma, Inc. Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma, Inc.

Background Current postresuscitative care after cardiac arrest (CA) does not address the cause of CA. We previously reported that asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) elicit unique injury signatures. We hypothesized that the early cytokine profiles of the serum, heart, and brain differ in response to ACA versus VFCA. Methods and Results Adult male rats were subjected to 10 minutes of either ACA or VFCA. Naives and shams (anesthesia and surgery without CA) served as controls (n=12/group). Asphyxiation produced an ≈4‐minute period of progressive hypoxemia followed by a no‐flow duration of ≈6±1 minute. Ventricular fibrillation immediately induced no flow. Return of spontaneous circulation was achieved earlier after ACA compared with VFCA (42±18 versus 105±22 seconds; P Conclusions Both models of CA resulted in marked systemic, heart, and brain cytokine responses, with similar degrees of change across the 2 CA insults. Changes in cytokine levels after CA were most pronounced in the striatum compared with other brain regions. These collective observations suggest that the amplitude of the changes in cytokine levels after ACA versus VFCA may not mediate the differences in secondary injuries between these 2 CA phenotypes.

Background Spinopelvic pathology has been identified as a potential risk factor for instability after total hip arthroplasty. Spinopelvic radiographic parameters used to diagnose spinopelvic disease may also impact optimal cup placement. The purpose of this study was to assess the arthroplasty surgeon accuracy in making spinopelvic measurements. Methods Five fellowship-trained or in-training arthroplasty surgeons reviewed 44 lateral lumbar radiographs in two sessions. All evaluators were instructed how to perform measurements but had little experience in doing so. Traditional measurements included the pelvic tilt (PT), pelvic incidence (PI), and sacral slope (SS), and novel measurements included the acetabular ante-inclination (AI) and pelvic femoral angle. Surgeon measurements were compared with those made by experienced engineers. intraclass coefficients (ICCs) were calculated and interpreted. Results The interobserver reliability for 4 of 5 of the spinopelvic parameters was good to excellent (ICC >0.75) with the highest reliability seen for PI measurement (ICC = 0.939). Only moderate interobserver reliability was observed for AI measurement (ICC = 0.559). Intraobserver reliability was the highest for the PI and SS, ranging from moderate to good (ICC, 0.718 to 0.896). The lowest intraobserver reliability was seen for the AI (ICC range, 0.026 to 0.545) and pelvic femoral angle (ICC range, 0.035 to 0.828). Surgeon measurements of PT and SS were compared with engineer measurements with extremely poor correlation observed (ICC Conclusion Surgeon intraobserver and interobserver reliability in making novel radiographic measurements was low compared with traditional radiographic measurements. Surgeon reliability in making traditional measurements of the PT and SS was very poor compared with experienced assessors using software-based measurements.

Co-design and co-engineering have the potential to improve the design of electronics packaging significantly. A co-designed approach moves away from the sequential approach of an electrical layout followed by a mechanical module design, and then the addition of a heat sink. Replacing it with an approach that addresses the electrical, thermal, and mechanical design simultaneously during the initial design. The goal is to evaluate the design space quickly, considering both the thermal and mechanical stress aspects together. ParaPower is a low order fast running parametric analysis tool, developed by the Army Research Laboratory (ARL), that allows rapid evaluation of package temperatures and coefficient of thermal expansion (CTE) induced stresses throughout the design space. The model uses a 3D nodal network to calculate device temperatures and thermal stresses. In order to rapidly evaluate the design space both the thermal and stress models must be reduced order and provide reasonable results on coarse grids. In the case of the stress model, the goal is a low order relationship between the temperatures and the CTE induced stresses. This paper compares three different low order models for stress. The first uses a more traditional planar module design. This assumes a substantial substrate or heat spreader as the base for the module assembly. The second model is less restrictive, eliminating the requirement for a substrate. The third model also eliminates the substrate requirement, but also allows for in-plane distribution of the stresses. The first two models do not account for the in-plane distribution. Two geometries are considered, a standard power module with a substantial substrate and a stacked novel module with no clear substrate layer. Results for both geometries and the three stress models are compared to finite element analysis (FEA) using SolidWorks, beginning with a thermal analysis followed by a stress analysis based on the temperature solution. All three models run roughly two orders of magnitude faster than the FEA and they correctly predict the trends in the CTE induced stresses.

Background The risk of early complications is high after monoblock acetabular metal-on-metal (MoM) THA revisions. However, there is a paucity of evidence regarding clinical complications after isolated head-liner exchange of modular MoM THA. Questions/purposes The purposes of this study were (1) to describe the frequency of early complications after an isolated head-liner exchange revision of modular MoM THA; and (2) to determine whether patients who experienced complications or dislocation after head-liner exchanges had higher serum chromium (Cr) or cobalt (Co) ion levels than those who did not. Methods A review of our institution's total joint registry retrospectively identified 53 patients who underwent 54 liner exchange revisions of a modular acetabular MoM THA. The study period was from April 2008 to April 2016 at a single tertiary care center. During this period, isolated head-liner exchanges (rather than more extensive revisions) were performed in patients if they did not have evidence of loosening of the acetabular or femoral components. Reasons for revision surgery included pain, mechanical symptoms, radiographic evidence of osteolysis, elevated serum metal ions, and MRI abnormalities with 40 of the 54 hips having pain or mechanical symptoms and 38 of 54 hips having multiple reasons for revision before surgery. Patients were excluded if they did not meet the minimum postrevision followup or had the modular liner exchange secondary to infection. All revisions were from a single manufacturer with one head-liner exchange of a MoM THA from another manufacturer excluded during the study period. The mean time from index MoM THA to modular exchange was 96 (SD ± 36) months. Because the focus of this study was early complications, we had a minimum 90-day followup duration for inclusion. Mean followup after revision was 15 months (SD ± 12); a total of 56% (30 of 54) had followup of at least 12 months' duration. Complications (dislocation, infection) and reoperations were obtained by chart review performed by individuals other than the treating physician(s). Serum metal ion levels were obtained before head-liner exchange. The median serum Cr and Co levels were 6 µg/L (range, 0-76 µg/L) and 12 µg/L (range, 0-163 µg/L), respectively. Results Of the 54 revision THAs, 15 (28%) developed complications. Nine (17%) occurred within 90 days of the revision surgery and 11 (20%) resulted in reoperation. The most common complication was dislocation (12 of 54 [22%]) with recurrent dislocation noted in eight of these 12 patients. All patients with recurrent dislocation continued to dislocate and underwent repeat revision. Patients with dislocation had higher median serum Cr and Co ion levels than those without dislocation (Cr: 24 [range, 11-76] versus 4 [range, 0-70], p = 0.001 [95% confidence interval {CI}, 10-57]; Co: 41 [range, 6-163] versus 8 [range, 0-133], p = 0.016 [95% CI, 6-141]). Three (6%) of the 54 patients underwent repeat surgery for deep space infection. Conclusions Complications and reoperations are common after modular head-liner exchange in the setting of a failed MoM THA. Our study likely underestimates the frequency of complications and revisions because the followup period in this report was relatively short. Dislocation is the most common complication and elevated serum metal ion levels may be a predictor of dislocation. These findings are concerning and surgeons should be aware of the high complication risk associated with this procedure. Level of evidence Level IV, therapeutic study.

Phosphoric acid fuel cells are successfully used as energy conversion technologies in stationary power applications. However, decreased proton conductivity and lower oxygen permeability of phosphoric-acid-imbibed membranes require prohibitive loadings of the traditional noble-metal-based electrocatalyst, such as platinum supported on carbon. Additionally, specific adsorption of phosphate anions on the catalyst results in a surface poisoning that further reduces electrocatalytic activity. Here we report a nonplatinum group metal (non-PGM) electrocatalyst as an alternative cathode electrocatalyst for oxygen reduction in phosphoric acid fuel cells. The non-PGM was prepared in a one-pot synthesis using a metal organic framework and iron salt precursor. Phosphate anion poisoning was monitored electrochemically and spectroscopically in reference to the current state-of-the-art Pt-based catalyst at room temperature. Unlike Pt-based catalysts that are prone to phosphate poisoning, the non-PGM electrocatalyst exhi...

Lewy body disorders are characterized by the emergence of α-synucleinopathy in many parts of the central and peripheral nervous systems, including in the telencephalon. Dense α-synuclein+ pathology appears in regio inferior of the hippocampus in both Parkinson’s disease and dementia with Lewy bodies and may disturb cognitive function. The preformed α-synuclein fibril model of Parkinson’s disease is growing in use, given its potential for seeding the self-propagating spread of α-synucleinopathy throughout the mammalian brain. Although it is often assumed that the spread occurs through neuroanatomical connections, this is generally not examined vis-à-vis the uptake and transport of tract-tracers infused at precisely the same stereotaxic coordinates. As the neuronal connections of the hippocampus are historically well defined, we examined the first-order spread of α-synucleinopathy three months following fibril infusions centered in the mouse regio inferior (CA2 + CA3), and contrasted this to retrograde and anterograde transport of the established tract-tracers FluoroGold and biotinylated dextran amines (BDA). Massive hippocampal α-synucleinopathy was insufficient to elicit memory deficits or loss of cells and synaptic markers in this model of early disease processes. However, dense α-synuclein+ inclusions in the fascia dentata were negatively correlated with memory capacity. A modest compensatory increase in synaptophysin was evident in the stratum radiatum of cornu Ammonis in fibril-infused animals, and synaptophysin expression correlated inversely with memory function in fibril but not PBS-infused mice. No changes in synapsin I/II expression were observed. The spread of α-synucleinopathy was somewhat, but not entirely consistent with FluoroGold and BDA axonal transport, suggesting that variables other than innervation density also contribute to the materialization of α-synucleinopathy. For example, layer II entorhinal neurons of the perforant pathway exhibited somal α-synuclein+ inclusions as well as retrogradely labeled FluoroGold+ somata. However, some afferent brain regions displayed dense retrograde FluoroGold label and no α-synuclein+ inclusions (e.g. medial septum/diagonal band), supporting the selective vulnerability hypothesis. The pattern of inclusions on the contralateral side was consistent with specific spread through commissural connections (e.g. stratum pyramidale of CA3), but again, not all commissural projections exhibited α-synucleinopathy (e.g. hilar mossy cells). The topographical extent of inclusions is displayed here in high-resolution images that afford viewers a rich opportunity to dissect the potential spread of pathology through neural circuitry. Finally, the results of this expository study were leveraged to highlight the challenges and limitations of working with preformed α-synuclein fibrils.

Triphenylene ligands hexasubstituted with amino or phenol groups afford two phases of electrically conductive layered two-dimensional metal–organic frameworks upon reaction with various metals. Regardless of the identity of the metal or chelating atom, π-stacking within the MOF layers is essential to achieve high electrical conductivity, redox activity, and catalytic activity.

Introduction. Graduate professional educational programs are very rigorous and challenging, often leading to increased physiological stress and perceived anxiety for the enrolled student. Stress and anxiety levels in physical therapy students are higher than that in their age and gender matched peers. The purpose of this study was to assess the impact of an animal-assisted intervention on stress and anxiety of entry-level physical therapist (PT) students prior to a laboratory practical exam. Subjects. Twenty-three first-year PT students (mean age 23.4 ± 1.70) participated in this study. Methods. A 15-20-minute intervention which either included a therapy dog or no therapy dog was performed prior to the students’ laboratory practical exam. Following the intervention, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and state anxiety measures using the State-Trait Anxiety Inventory (STAI) were obtained. Results were compared to baseline measures as well as between each of four intervention trials using repeated measures ANOVA or Freidman test (alpha level of p 0.005). Discussion and Conclusion. The results of this study indicate that animal-assisted interventions may be beneficial in reducing perceived anxiety for students in graduate professional educational programs prior to an examination.

The fluoroscopically assisted direct anterior approach for total hip arthroplasty has gained interest in recent years. One of the perceived advantages is the use of fluoroscopy to aid in the positioning of implants. The purpose of this study was to measure the radiation entrance surface dose to anatomically important areas of both patients and surgeons during direct anterior approach total hip arthroplasty.Radiation dosimetry badges were placed at the sternal notch and pubic symphysis of 50 patients undergoing direct anterior approach total hip arthroplasty. Badges were also placed on the surgeons outside of their lead aprons at the level of the thyroid. Three fellowship-trained arthroplasty surgeons were involved in the study. Radiation exposure of each badge was measured after each case (surgeon and patient). The cumulative dose was also calculated for the surgeons. To limit surgeon bias during the study, 50 consecutive direct anterior approach total hip arthroplasties that occurred prior to this study were analyzed for total fluoroscopic dose and time and served as a control group.Forty-five subjects met study criteria. In the study group, 1 patient had a detectable thyroid exposure equal to 1 mrem. Seven patients had a detectable radiation entrance surface dose at the pubic symphysis (range, 1 to 7 mrem). No radiation entrance surface dose was detectable in the remaining 44 patients at the sternal notch and 38 patients at the pubic symphysis. Surgeons in the study did not experience a detectable radiation entrance surface dose. The mean fluoroscopic time was 13.72 seconds (range, 6.7 to 28.7 seconds). The mean patient radiation exposure was 178 mrem (range, 54 to 526 mrem).This study demonstrates that during direct anterior approach total hip arthroplasty, the mean patient entrance surface dose at the pubic symphysis and the sternal notch is not detectable in most patients. The mean patient exposure in this study during direct anterior approach total hip arthroplasty was 178 mrem, which is less than a single pelvic radiograph (600 mrem). No surgeon in our study demonstrated a detectable radiation entrance surface dose. Our data suggest that direct anterior approach total hip arthroplasty typically results in a negligible or very low dose of absorbed radiation exposure to the patient and the surgeon.We believe this study to have clinical relevance because both patients and surgeons have evidence that utilization of fluoroscopy during direct anterior total hip replacement places both parties at a relatively low radiation exposure risk.

Dopamine loss and motor deficits in Parkinson's disease typically commence unilaterally and remain asymmetric for many years, raising the possibility that endogenous defenses slow the cross-hemispheric transmission of pathology. It is well-established that the biological response to subtoxic stress prepares cells to survive subsequent toxic challenges, a phenomenon known as preconditioning, tolerance, or stress adaptation. Here we demonstrate that unilateral striatal infusions of the oxidative toxicant 6-hydroxydopamine (6-OHDA) precondition the contralateral nigrostriatal pathway against the toxicity of a second 6-OHDA infusion in the opposite hemisphere. 6-OHDA-induced loss of dopaminergic terminals in the contralateral striatum was ablated by cross-hemispheric preconditioning, as shown by two independent markers of the dopaminergic phenotype, each measured by two blinded observers. Similarly, loss of dopaminergic somata in the contralateral substantia nigra was also abolished, according to two blinded measurements. Motor asymmetries in floor landings, forelimb contacts with a wall, and spontaneous turning behavior were consistent with these histological observations. Unilateral 6-OHDA infusions increased phosphorylation of the kinase ERK2 and expression of the antioxidant enzyme CuZn superoxide dismutase in both striata, consistent with our previous mechanistic work showing that these two proteins mediate preconditioning in dopaminergic cells. These findings support the existence of cross-hemispheric preconditioning in Parkinson's disease and suggest that dopaminergic neurons mount impressive natural defenses, despite their reputation as being vulnerable to oxidative injury. If these results generalize to humans, Parkinson's pathology may progress slowly and asymmetrically because exposure to a disease-precipitating insult induces bilateral upregulation of endogenous defenses and elicits cross-hemispheric preconditioning.

© 2017 American Chemical Society. Establishing catalytic structure-function relationships introduces the ability to optimize the catalyst structure for enhanced activity, selectivity, and durability against reaction conditions and prolonged catalysis. Here we present experimental and computational data elucidating the mechanism for the O2reduction reaction with a conductive nickel-based metal-organic framework (MOF). Elucidation of the O2reduction electrokinetics, understanding the role of the extended MOF structure in providing catalytic activity, observation of how the redox activity and pKaof the organic ligand influences catalysis, and identification of the catalyst active site yield a detailed O2reduction mechanism where the ligand, rather than the metal, plays a central role. More generally, familiarization with how the structural and electronic properties of the MOF influence reactivity may provide deeper insight into the mechanisms by which less structurally defined nonplatinum group metal electrocatalysts reduce O2.

Objective To examine the safety and efficacy of a high-intensity (HI) progressive rehabilitation protocol beginning 4 days after total knee arthroplasty (TKA) compared to a low-intensity (LI) rehabilitation protocol. Methods A total of 162 participants (mean ± SD ages 63 ± 7 years; 89 women) were randomized to either the HI group or LI group after TKA. Key components of the HI intervention were the use of progressive resistance exercises and a rapid progression to weight-bearing exercises and activities. Both groups were treated in an outpatient setting 2 to 3 times per week for 11 weeks (26 total sessions). Outcomes included the stair climbing test (SCT; primary outcome), timed-up-and-go (TUG) test, 6-minute walk (6MW) test, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 12-item Short Form health survey (SF-12), knee range of motion (ROM), quadriceps and hamstring strength, and quadriceps activation. Outcomes were assessed preoperatively and at 1, 2, 3 (primary end point), 6, and 12 months postoperatively. Results There were no significant differences between groups at 3 or 12 months in SCT, TUG, 6MW, WOMAC scores, knee ROM, quadriceps and hamstrings strength, quadriceps activation, or adverse event rates. By 12 months, outcomes on the 6MW, TUG, WOMAC, SF-12, quadriceps and hamstring strength, and quadriceps activation had improved beyond baseline performance in both groups. Conclusion Both the HI and LI interventions were effective in improving strength and function after TKA. HI progressive rehabilitation is safe for individuals after TKA. However, its effectiveness may be limited by arthrogenic muscular inhibition in the early postoperative period.

Despite the clear importance of the operative report in the electronic medical record, few studies have addressed the quality.We prospectively evaluated 300 consecutive patients undergoing primary total joint arthroplasties for operative report errors utilizing three different forms of documentation (standard dictation vs. templated dictation vs. a computer registry database generated operative report). The three types of reports were evaluated for errors which were classified as either major or minor.There were significantly more total errors in the standard dictation group compared to both the computer registry database generated (p0.001) and the templated operative reports (p0.001). Major errors were significantly reduced in the database generated reports compared to the templated (p0.001) and standard dictation groups (p0.001). There were significantly more minor errors in the standard dictation group (p0.001) compared to the other two groups. No statistically significant differences in major errors were noted when comparing standard vs. templated operative reports. There was no difference in minor or total errors between the database generated and templated operative reports.The use of a computer registry database generated operative report resulted in fewer major errors versus a templated or standard dictated operative report. Further research is warranted in this area to validate these findings across subspecialties and institutions.

Background Patellofemoral (PF) complications following total knee arthroplasty continue to occur. Outcomes are influenced by implant design, size and alignment in addition to patient factors. The objective of this study was to assess the effect of implant design, specifically round versus oval dome patellar components, on size selected and bony coverage in a population of 100 patients. Methods Intraoperative assessments of patella component size were performed using surgical guides for round and oval designs. Digital images of the resected patellae with and without guides were calibrated and analyzed to measure bony coverage. Lastly, the medial–lateral location of the median ridge was assessed in the native patella and compared to the positioning of the apex of the patellar implants. Results In 82% of subjects, a larger oval implant was selected compared to a round. Modest, but statistically significant, differences were observed in selected component coverage of the resected patella: 82.7% for oval versus 80.9% for round. Further, positioning of the apex of oval patellar components reproduced the median ridge of the native patella more consistently than for round components. Conclusions These findings characterized how implant design influenced size selection and coverage in a population of patients. The ability to “upsize” with oval dome components led to increases in bony coverage and better replication of the median ridge compared to round components. Quantifying the interactions between implant design, sizing and coverage for a current implant system in a population of patients supports surgical decision-making and informs the design of future implants.

Background Stress shielding is an uncommon complication associated with primary total knee arthroplasty. Patients are frequently identified radiographically with minimal clinical symptoms. Very few studies have evaluated risk factors for postoperative medial tibial bone loss. We hypothesized that thicker cobalt–chromium tibial trays are associated with increased bone loss. Methods We performed a retrospective review of 100 posterior stabilized, fixed-bearing total knee arthroplasty where 50 patients had a 4-mm-thick tibial tray (thick tray cohort) and 50 patients had a 2.7-mm-thick tibial tray (thin tray cohort). A clinical evaluation and a radiographic assessment of medial tibial bone loss were performed on both cohorts at a minimum of 2 years postoperatively. Results Mean medial tibial bone loss was significantly higher in the thick tray cohort (1.07 vs 0.16 mm; P = .0001). In addition, there were significantly more patients with medial tibial bone loss in the thick tray group compared with the thin tray group (44% vs 10%, P = .0002). Despite these differences, there were no statistically significant differences in range of motion, knee society score, complications, or revision surgeries performed. Conclusion A thicker cobalt–chromium tray was associated with significantly more medial tibial bone loss. Despite these radiographic findings, we found no discernable differences in clinical outcomes in our patient cohort. Further study and longer follow-up are needed to understand the effects and clinical significance of medial tibial bone loss.

Study Design Systematic review. Introduction It is accepted that the etiology of carpal tunnel syndrome (CTS) is multifactorial. One of the most commonly accepted etiologic factors for CTS is compromise of the kinematic behavior and excursion of the median nerve. Purpose of the Study The objective of this systematic review was to establish if there is a relationship between impaired median nerve excursion and CTS. Methods A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, was conducted. Studies were sought where in vivo median nerve excursion was compared between people with CTS to an appropriate control group. Quality appraisal for each study was conducted using the Newcastle-Ottawa Scale by 2 independent evaluators. Results Ten case-control studies using ultrasound imaging to quantify median nerve excursion were included. All studies were rated as of “moderate” methodologic quality having scored 6 or 7 (of 9 stars) for the Newcastle-Ottawa Scale. Seven of the 10 studies concluded that median nerve excursion was reduced in a CTS population when compared with controls. Conclusion The literature suggests that median nerve excursion is reduced in people with CTS when compared with healthy controls. Level of Evidence 3a.

Aims The aim of this study was to determine whether closed suction drain (CSD) use influences recovery of quadriceps strength and to examine the effects of drain use on secondary outcomes: quadriceps activation, intra-articular effusion, bioelectrical measure of swelling, range of movement (ROM), pain, and wound healing complications. Patients and Methods A total of 29 patients undergoing simultaneous bilateral total knee arthroplasty (TKA) were enrolled in a prospective, randomized blinded study. Patients were randomized to receive a CSD in one limb while the contralateral limb had the use of a subcutaneous drain (SCDRN) without the use of suction (‘sham drain’). Isometric quadriceps strength was collected as the primary outcome. Secondary outcomes consisted of quadriceps activation, intra-articular effusion measured via ultrasound, lower limb swelling measured with bioelectrical impendence and limb girth, knee ROM, and pain. Outcomes were assessed preoperatively and postoperatively at day two, two and six weeks, and three months. Differences between limbs were determined using paired Student’s t-tests or Wilcoxon’s signed-rank tests. Results No significant differences were identified between limbs prior to surgery for the primary or secondary outcomes. No significant differences in quadriceps strength were seen between CSD and SCDRN limbs at postoperative day two (p = 0.09), two weeks (primary endpoint) (p = 0.7), six weeks (p = 0.3), or three months (p = 0.5). The secondary outcome of knee extension ROM was significantly greater in the CSD limb compared with the SCDRN (p = 0.01) at two weeks following surgery, but this difference was absent at all other intervals. Secondary outcomes of quadriceps activation, intra-articular effusion, lower limb swelling, and pain were not found to differ significantly at any timepoint following surgery. Conclusion The use of CSD during TKA did not influence quadriceps strength, quadriceps activation, intra-articular effusion, lower limb swelling, ROM, or pain. These results have limited drain use by the authors in primary uncomplicated TKA. Cite this article: Bone Joint J 2019;101-B (7 Supple C):84–90

Co-design and co-engineering have the potential to significantly advance the state of the art of electronics packaging. A key enabling capability of co-design are design tools which allow quick parametric design across various design spaces. ARL's ParaPower tool allows quick parametric thermo-mechanical design analysis of most rectilinear designs using a 3D thermal resistor network for both steady-state and transient heat loads. This work expands the ParaPower capabilities by allowing internal boundary cavity (IBC) features into the network structure. IBCs can be placed anywhere in the 3D rectilinear geometry and include two distinct boundary parameters: (1) a surface heat transfer coefficient and (2) an ambient temperature. Adding the IBC functionality to the network model significantly increases the design flexibility by permitting internal convection paths, non-rectilinear geometries, and heat sink geometry evaluation. This paper presents the IBC equations and illustrates the parametric capability by evaluating the effects of convection coefficient and heat sink material. The ability to quickly assess the thermal and stress effects of a wide variety of power module design parameters during the initial design process - with reasonable results and without the complexity of a full FEA analysis - can significantly improve the final design.

A Cu-azolate metal-organic framework (MOF) uptakes stoichiometric loadings of Groups 1 and 2 metal halides, demonstrating efficient reversible release and reincorporation of immobilized anions within the framework. Ion-pairing interactions lead to anion-dependent Li

A 44-year-old female presented with a chief complaint of left knee pain and dysfunction. The patient had a complex surgical history including patellar fracture repair, subsequent patellar ligament repair, and ultimately allograft reconstruction which was complicated by septic arthritis requiring graft resection. On presentation to our clinic, she was noted to have significant degenerative disease in addition to chronic extensor mechanism deficiency. She underwent primary total knee arthroplasty with concomitant tibial tubercle osteotomy and advancement. The patient has had an excellent result postoperatively including return of full range of motion without residual extensor lag.

Background Use of leukocyte esterase (LE) testing of synovial fluid as an adjunct to the infection workup in total joint arthroplasty patients has been advocated. The purpose of this study was to determine the false positive rate of this test. Methods Two hundred patients with the diagnosis of degenerative osteoarthritis undergoing a total knee arthroplasty were identified for this study. The knee joint was aspirated under sterile conditions before performing the total knee arthroplasty. The fluid was analyzed with an LE reagent strip. Results There were 27 bloody and 17 dry aspirations. One hundred forty-nine patients produced an aspiration that allowed for LE testing. There was 1 positive LE result. The specificity of the LE test was found to be 99.3%. Conclusion These data suggest the LE strip as a part of the workup for infection in a native knee should yield few false positive results.

A low order fast running parametric analysis tool, ParaPower, was used to arrive at the design for a novel high voltage module. The low order model used a 3D nodal network to calculate device temperatures and thermal stresses. The model assumed heat flux generated near the top surface of each device which is then conducted through the packaging structure and removed by convection. The temperature distribution is used to calculate thermal stresses throughout the package. This co-design modeling tool, developed for rectilinear geometries, allowed a rapid evaluation of the package temperatures and CTE induced stresses throughout the design space. However, once the final design configuration was determined a detailed finite element analysis was performed to validate the design. This paper compares the results obtained using ParaPower to the FEA, demonstrating the usefulness of the parametric analysis tool. Results for both temperature and CTE induced stress are compared. Two different stress models are evaluated. One based on the more traditional planar module design, which assumes a substantial substrate or heat spreader on which the module is assembled. The other model is less restrictive, eliminating the requirement for a substrate. The FEA modeling was performed using SolidWorks beginning with a thermal analysis followed by a stress analysis based on the temperature solution. Both the values and the trends of the temperatures and stresses were evaluated. The temperature results agreed to within 3.2°C. The trends and sign of the stresses were correctly predicted, but the magnitudes were not. One of the significant advantages of ParaPower is the speed of the computation. The run time for the parametric analysis was roughly two orders of magnitude faster than the FEA. This made it possible to build the model and complete the parametric analysis of roughly 500 runs in less than a day.

Co-design and co-engineering have the potential to significantly advance the state of the art of electronics packaging. A co-designed approach moves away from a sequential design approach (electrical layout, then a mechanical module design, and finally the addition of a heat sink) and replaces it with an approach where the electrical, thermal, and mechanical domains are all simultaneously designed for during the initial design. This paper demonstrates how a co-design approach can be used to design an electronics module. This work shows the design and fabrication of a 30 kV module using two aspects of co-design: (1) multi-functional components (MFCs) and (2) quick parametric analysis. There is a need for advanced high voltage electronics packages due to the recent development of high voltage (15–30 kV) single-die silicon carbide (SiC) power devices to realize their full potential. This paper describes a 30 kV module with integrated heat sinks, double sided device cooling, and an air cooled heat sink which removes heat from four sides of the module. The module has numerous MFCs allowing a compact form factor and efficient design. In addition, the geometry and materials selections were based off a co-design tool which allows quick parametric analysis for both thermal and stress. This paper demonstrates the capabilities and benefits of moving away from a traditional design approach and implementing a co-design methodology.

Introduction Hard-on-hard (HoH) bearing surfaces in total hip arthroplasty (THA) are commonly utilized in younger patients and may decrease mechanical wear compared to polyethylene bearing surfaces. To our knowledge, no study has prospectively compared the 2 most common HoH bearings, ceramic-on-ceramic (CoC) and metal-on-metal (MoM) THA. Materials and Methods We prospectively enrolled 40 patients to undergo an MoM THA and 42 patients to undergo a CoC THA utilizing the same acetabular component. Patients were followed up for a minimum of 2 years. Comparative outcomes included clinical scores, revision or reoperation for any reason, complication rates, and radiographic outcomes. Results The average follow-up was significantly longer in the CoC cohort (94 vs 74 months; P = .005). The CoC cohort had significantly improved Harris Hip Scores (95 vs 84; P = .0009) and pain scores (42 vs 34; P = .0003). The revision (0% vs 31%; P = .0001), reoperation (7.5% vs 36%; P = .004), and complication rates (10% vs 56%; P = .0001) were significantly lower in the CoC cohort. There were no statistically significant differences in radiographic parameters. Conclusion The clinical outcomes in the CoC cohort exceeded the MoM cohort. It is unlikely that another prospective comparative study of HoH THAs will be conducted. Our midterm results support the use of CoC THA as a viable option that may reduce long-term wear in younger patients. Close surveillance of MoM THA patients is recommended considering the higher failure and complication rates reported in this cohort.

This work presents an easy to use approach to quickly estimate the device temperatures and thermal stresses in a generic high power module. A low order model was developed in MATLAB using a combination of numerical-analytical approach and a 3D nodal resistor network to calculate device temperatures and thermal stresses. The model assumes a heat flux generated at the top of each device which is dissipated through the packaging structure and removed by convection. The temperature distribution is used to calculate thermal stresses throughout the package. This method eliminates computer aided drawings (CAD) in favor of numerical parameters that can be easily and quickly varied over a wide range. The resistor network solves quickly in MATLAB, enabling fast, iterative thermal analyses and design through parametric studies of the chip dimensions, number of chips, chip layout, material types, cooling solutions, etc. The model is adaptable to any number of devices and board layers. The MATLAB model reduced the computational time by 97% compared to an equivalent SOLIDWORKS finite element analysis (FEA) model and that does not include the time required to generate the CAD model and verify mesh convergence and mesh independence. Temperatures from the network model were within 5°C and stresses were within 30% of the values obtained from the FEA model. The ability to quickly assess the thermal and stress effects of a wide variety of power module design parameters during the initial design process, without the complexity of a full FEA analysis, with reasonable results can significantly improve the final module.

Over 70,000 Burmese refugees have resettled in the United States in the past decade. While Burmese adolescents quickly acculturate into American society, their perspectives on health are not well-known. The purpose of this study was to identify adolescent Burmese refugee perspectives on determinants of health and health-related experiences after resettlement. In this qualitative study, Burmese adolescents took photographs depicting health-related experiences that were used as elicitation tools during focus groups. These discussions were recorded, transcribed, and analyzed for themes. Participants described positive determinants of health, including family and church. Rampant tobacco use was identified by the participants as a determinant of poor health within the Burmese community. Notably, the participants were proud to serve as liaisons within their community, despite the stressful nature of this role. Our results highlight the need to screen this population for anxiety, secondary to serving as a liaison for their community, as well as tobacco use.

This study uses CFD to consider the effects of obstructions (bosses) on the fluid flow and heat transfer in finned heat sinks used for cooling electronic components. In particular, the effect of bosses, used for mounting components, on the fluid flow distribution and temperature distribution in the heat sink are evaluated. A typical heat sink has fins sandwiched between top and bottom plates, with electronic components mounted on the plates. The top and bottom plates spread the heat generated in the components to reduce the local heat flux. The fins substantially increase the heat transfer area, reducing the temperature rise from the coolant to the top and bottom plates. In this case a uniform distribution of flow across the heat sink can be achieved and there will be no localized hot spots. Ideally there are no protrusions into the finned portion of the heat sink which would cause disruptions in the uniform flow through the heat sink. However, a boss may be needed to bolt a component to the heat sink. The presence of the boss has three effects on the heat sink performance. The boss disrupts the flow in its immediate vicinity, increasing the thermal resistance. This will cause an increase in operating temperature at that location. In addition, the boss will change the flow distribution in the heat sink. Locations upstream and downstream of the boss may see reduced flow due to the obstruction, which in turn will cause an increase in operating temperature for these areas of the heat sink. Finally, the change in flow distribution may increase the pressure drop through the entire heat sink, increasing the power required to operate the system. The purpose of this study is to numerically evaluate the clearance requirements around circular bosses. Comparisons between an unobstructed heat sink and a heat sink with an obstruction are made for the maximum component temperature rise, the pressure drop and the flow distribution. Clearance ratios, diameter of the fin cut out to boss diameter, were varied from 1.1 to 3.3. The Reynolds number for the flow was varied from roughly 3000 to 70,000 based on the hydraulic diameter of flow passage.

Fontan patients managed with warfarin are at risk not only for thrombotic events, but also for bleeding episodes as a consequence of anticoagulation treatment. The aim of this study was to determine whether time spent in patient specified therapeutic range (TTR), when managed in a cardiology-based pharmacist managed anticoagulation clinic (PMAC), is a useful target metric for monitoring, as well as improving outcomes. A single center retrospective review was conducted evaluating TTR of all Fontan patients (n = 45) on warfarin managed in our outpatient cardiology pharmacist managed anticoagulation clinic (PMAC) during a 19 month time frame. The primary outcome was time spent within, above, and below therapeutic range. Secondary outcomes were thrombotic event (TE) incidence pre- and post PMAC enrollment and bleeding event incidence during PMAC management. Of the Fontan patients included, 55.6% were male and the median age at latest anticoagulation clinic follow-up was 19 years (IQR 13, 29). A composite 52.9 patient years of warfarin therapy was evaluated during the study time frame. The mean TTR for patients was 84.1 ± 5.2%. The most frequent reasons for non-therapeutic INRs were diet changes (42.8%), medication non-compliance (13.7%), and drug interactions (8.8%). Only one TE occurred during the study time frame. The incidence of TE in this population was decreased after PMAC enrollment (1 per 52.9 patient year versus 1 event per 17.4 patient year; p

Background: The medial tibial reduction osteotomy (MTRO) was introduced to achieve coronal ligamentous balance in total knee arthroplasty (TKA) patients with substantial preoperative varus deformity. Limited data exists on the outcomes of patients requiring an MTRO. This study compares outcomes of a matched cohort of patients that either required or did not require an MTRO during TKA. Methods: A retrospective review was performed on 67 patients that underwent an MTRO during primary TKA to achieve coronal balance. This patient population was matched 1:1 to another cohort of TKA patients by age, gender, and BMI that did not require an MTRO. A clinical and radiographic evaluation was utilized to compare the two cohorts. Results: Preoperatively, the tibiofemoral angle was 3.42° valgus versus 6.12° varus in the control and MTRO cohorts respectively (p=0.01). Mean postoperative tibiofemoral angles were 3.40° versus 2.43° valgus respectively. Postoperative Knee Society Scores were superior in the MTRO cohort (183.84 versus 174.58; p=0.04). Intraoperatively, no superficial MCL releases were required to achieve coronal balance in either cohort. Complications were similar and limited in both groups. Medial tibial bone resorption was observed in 64% of MTRO subjects averaging 2.02mm versus only 0.3mm in the control cohort ( p=0.01). Conclusion: Patients requiring an MTRO achieved similar alignment and superior knee scores compared to a control cohort with less varus deformity. This procedure eliminated the need for release of the superficial MCL. Resorption of medial tibial bone was commonly observed, possibly secondary to saw-induced thermal necrosis associated with performing an MTRO.