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Background: Biomedtrix BFX ® cementless total hip replacement (THR) requires the use of femoral broaches to prepare a press-fit envelope within the femur for subsequent stem insertion. Current broaches contain teeth that crush and remove cancellous bone; however, they are not particularly well-suited for broaching sclerotic (corticalized) cancellous bone. In this study, three tooth designs [Control, TG1 (additional V-grooves), TG2 (diamond tooth pattern)] were evaluated with a quasi-static testing protocol and polyurethane test blocks simulating normal and sclerotic bone. To mimic clinical broaching, a series of five sequential broach insertions were used to determine cumulative broaching energy (J) and peak loads during broach insertion. To determine the effect of broach tooth design on THR stem insertion, a BFX ® stem was inserted into prepared test blocks and insertion and subsidence energy and peak loads were determined., Results: Broach tooth design led to significant differences in broaching energy and peak broaching loads in test blocks of both densities. In low density test blocks, TG1 required the lowest cumulative broaching energy (10.76 ±0.29 J), followed by Control (12.18 ±1.20 J) and TG2 (16.66 ±0.78 J) broaches. In high density test blocks, TG1 required the lowest cumulative broaching energy (32.60 ±2.54 J) as compared to Control (33.25 ±2.16 J) and TG2 (59.97 ±3.07 J).  During stem insertion and subsidence testing, stem insertion energy for high density test blocks prepared with Control broaches was 14.53 ± 0.81 J, which was significantly lower than blocks prepared with TG1 (22.53 ± 1.04 J) or TG2 (19.38 ± 3.00 J) broaches. For stem subsidence testing in high density blocks, TG1 prepared blocks required the highest amount of energy to undergo subsidence (14.49 ± 0.49 J), which was significantly greater than test blocks prepared with Control (11.09 ±0.09 J) or TG2 (12.57 ± 0.81 J) broaches., Conclusions: The additional V-grooves in TG1 broaches demonstrated improved broaching performance while also generating press-fit envelopes that were more resistant to stem insertion and subsidence. TG1 broaches may prove useful in the clinical setting; however additional studies that more closely simulate clinical broach impaction are necessary prior to making widespread changes to THR broaches., (© 2024. The Author(s).)

Introduction: Indoor tanning is a major modifiable risk factor in the development of both melanoma and nonmelanoma skin cancers. Investigation of behavior-altering interventions is an area of active research. As with other preventive measures, screening of high-risk populations can be an important aspect of a multimodality public health intervention. This study sought to further the limited understanding of indoor tanning screening practices in the primary care setting., Methods: Physicians practicing within the scope of primary care in the northeast were surveyed in 2022 on practice patterns around the frequency of indoor tanning screening, barriers encountered with implementing screening, and actions taken with a positive screen. Research methodology adhered to the Joanna Briggs Institute critical appraisal checklist., Results: Of 26 primary care physicians, only 7.7% routinely screened for indoor tanning. Barriers identified included time limitations (76.9%) and prioritization of other health concerns (96.2%). All primary care physicians (100%) reacted to reports of indoor tanning with an intervention, most commonly counseling on the risks of indoor tanning (92.6%)., Conclusions: This data suggest that screening for indoor tanning use could be improved. The authors recommend the incorporation of a standardized screening question regarding indoor tanning in intake forms., (© 2024 The Author(s).)

Estimation of the hip joint center in ovine biomechanical analysis is often overlooked or estimated using a marker on the greater trochanter which can result in large errors that propagate through subsequent analyses. The purpose of this study was to develop a novel method of estimating the hip joint centers in sheep to facilitate more accurate analysis of ovine biomechanics. CT scans from 16 sheep of varying ages, weight, sex, and phenotypes were acquired and the data was used to calculate the known hip joint center by sphere fitting the femoral head. Anatomical measurements and additional subject information were used to create a variety of regression models to estimate the hip joint centers in absence of CT data. The best regression equation created utilized markers placed on the tuber coxae and tuber ischii of the pelvis and resulted in a mean 3D Euclidean distance error of 6.43 ± 2.22 mm (mean ± standard deviation) between the known and estimated hip joint center. The regression models produced allow for more detailed, accurate and robust analysis of sheep biomechanics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a (CAG) repeat expansion in the coding sequence of ATXN1 . The primary mechanism of disease in SCA1 is toxic gain of function by polyglutamine-expanded mutant ATXN1 and is compounded by partial loss of wild-type function. Addressing both disease mechanisms, we have shown that virally expressed RNA interference targeting ATXN1 can both prevent and reverse disease phenotypes in SCA1 mice, and that overexpression of the ATXN1 homolog, ataxin 1-like (ATXN1L), improves disease readouts when delivered pre-symptomatically. Here, we combined these therapeutic approaches into two, dual component recombinant adeno-associated virus (rAAV) vectors and tested their ability to reverse disease in symptomatic SCA1 mice using behavior, pathological, and next-generation sequencing assays. Mice treated with vectors expressing human ATXN1L (hATXN1L) alone showed motor improvements and changes in gene expression that reflected increases in pro-development pathways. When hATN1L was combined with miS1, a previously validated microRNA targeting h ATXN1 , there was added normalization of disease allele-induced changes in gene expression along with motor improvements. Our data show the additive nature of this two-component approach for a more effective SCA1 therapy., Competing Interests: B.L.D. is a founder of Spark Therapeutics and Spirovant Sciences. She serves an advisory role and/or receives sponsored research support for her laboratory from Roche, Novartis, Homology Medicines, Resilience, Spirovant Sciences, Saliogen, Patch Bio, Panorama Medicines, and Voyager Therapeutics., (© 2022 The Authors.)

Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. STATEMENT OF SIGNIFICANCE: Current treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential "off-the-shelf" surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Push-out tests are frequently used to evaluate the bone-implant interfacial strength of orthopedic implants, particularly dental and craniomaxillofacial applications. There currently is no standard method for performing push-out tests on calvarial models, leading to a variety of inconsistent approaches. In this study, fixtures and methods were developed to perform push-out tests in accordance with the following design objectives: (i) the system rigidly fixes the explanted calvarial sample, (ii) it minimizes lateral bending, (iii) it positions the defect accurately, and (iv) it permits verification of the coaxial alignment of the defect with the push-out rod. The fixture and method was first validated by completing push-out experiments on 30 explanted murine cranial caps and two explanted leporine cranial caps, all induced with bilateral sub-critical defects (5.0 mm and 8.0 mm nominal diameter for the murine and leporine models, respectively). Defects were treated with an autograft (i.e., excised tissue flap), a shape memory polymer (SMP) scaffold, or a PEEK implant. Additional validation was performed on 24 murine cranial caps induced with a single, unilateral critically-sized defect (8.0 mm nominal diameter) and treated with an autograft or a SMP scaffold.•A novel fixture was developed for performing push-out mechanical tests to characterize the strength of a bone-implant interface in calvarial defect repair.•The fixture uses a 3D printed vertical clamp with mating alignment component to fix the sample in place without inducing lateral bending and verify coaxial alignment of push-out rod with the defect.•The fixture can be scaled to different calvarial defect geometries as validated with 5.0 mm bilateral and 8.0 mm single diameter murine calvarial defect model and 8.0 mm bilateral leporine calvarial defect model., (© 2021 The Authors. Published by Elsevier B.V.)

Neuronal tau reduction confers resilience against β-amyloid and tau-related neurotoxicity in vitro and in vivo. Here, we introduce a novel translational approach to lower expression of the tau gene MAPT at the transcriptional level using gene-silencing zinc finger protein transcription factors (ZFP-TFs). Following a single administration of adeno-associated virus (AAV), either locally into the hippocampus or intravenously to enable whole-brain transduction, we selectively reduced tau messenger RNA and protein by 50 to 80% out to 11 months, the longest time point studied. Sustained tau lowering was achieved without detectable off-target effects, overt histopathological changes, or molecular alterations. Tau reduction with AAV ZFP-TFs was able to rescue neuronal damage around amyloid plaques in a mouse model of Alzheimer's disease (APP/PS1 line). The highly specific, durable, and controlled knockdown of endogenous tau makes AAV-delivered ZFP-TFs a promising approach for the treatment of tau-related human brain diseases., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background A comparative biomechanical analysis of two distal biceps tendon repair techniques was performed: a single suture tension slide technique (TST) and two suture double tension slide (DTS) technique. Methodology Ten matched pairs of fresh frozen human cadaveric elbows (20 elbows) were randomly separated into two cohorts for distal biceps tendon repair. One cohort underwent the TST, and the other underwent the DTS technique. The tendon was preconditioned with cyclic loading from 0° to 90° at 0.5 Hz for 3,600 cycles with a 50 N load. The specimens were then loaded to failure at a rate of 1 mm/s. The difference in the load to failure between the groups was analyzed using the Student's t test. The mode of failure was compared between groups using the chi-square test. All p-values were reported with significance set at p < 0.05. Results Overall, 77.8% of the included matched pairs demonstrated greater load to failure in the DTS group. The mean load to failure in the DTS group was 383.3 ± 149.3 N compared to 275.8 ± 98.1 N in the TST group (p = 0.13). The DTS specimens failed at the tendon (5/9), suture (3/9), and bone (1/9). The TST specimens failed at the tendon (4/9) and suture (5/9) only. There was no significant difference in failure type between groups (p = 0.76). Conclusions DTS demonstrates a similar to greater load to failure compared to TST with a trend towards statistical significance. The redundancy provided by the second suture has an inherent advantage without compromising the biomechanical testing., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Sochacki et al.)

Uniaxial testing remains the most common modality of mechanical analysis for biological and other soft materials; however, biaxial testing enables a more comprehensive understanding of these materials' mechanical behavior. In recent years, a number of commercially available biaxial testing systems designed for biological materials have been produced; however, there are common limitations that are often associated with using these systems. For example, the range of allowable sample geometries are relatively constrained, the clamping systems are relatively limited with respect to allowable configurations, the load and displacement ranges are relatively small, and the software and control elements offer relatively limited options. Due to these constraints, there are significant benefits associated with designing custom biaxial testing systems that meet the technical requirements for testing a broad range of materials. Herein we present a design for a biaxial testing system with capabilities that extend beyond those associated with typical commercially available systems. Our design is capable of performing uniaxial tests, traditional biaxial tests, and double lap shear (simple shear) tests, in either a displacement or load control mode. Testing protocols have been developed and proof-of-concept experiments have been performed on commercially available silicone membranes and rat abdominal skin samples., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Repeated endoscopic access to the abdominal cavity of animal models is useful for a variety of research applications. However, repeated surgical access may affect the welfare of the animal and compromise results. We present the design and benchtop manufacturing process for a self-sealing endoscopic port requiring surgical incision only at implantation. It can be used for repeated body cavity access over a long time period. This device reduces costs, animals required for a given study, and potential suffering for each animal. This novel endoscopic port is designed for low-cost benchtop manufacturing without expensive equipment such as injection molding facilities. Devices manufactured using the method described in this work have been implanted successfully in hen models for investigation of ovarian cancer for over two years. All work followed Texas A&M University institutional guidelines and was covered under Animal Use Protocol 2017-0172, approved by TAMU Animal Care and Use Committee (IACUC). This method can be translated to produce similar devices for use in other small animal models besides the galline model used in this work. This method can be used to produce devices for slightly different purposes than repeated endoscopic access, such as production of an entry port for surgical tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Distal biceps tendon ruptures are thought to be secondary to an acute forceful eccentric load on a degenerative tendon. Nonoperative treatment following rupture leads to significantly decreased forearm supination and elbow flexion strength. There are several techniques described in the literature for repair. This article describes, with video illustration, distal biceps tendon repair using a double tension slide technique with 2 No. 2 high-tension nonabsorbable composite sutures., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier.)

Biologic tissues are complex materials that come in many forms and perform a variety of functions. They vary widely in composition and mechanical properties, and determination of the mechanical properties of tissues is of interest to those trying to engineer tissues to restore missing function. In performing experiments to characterize the mechanical properties of biologic tissues, there is no single solution to clamping tissues or tissue engineered constructs for mechanical testing. Various clamping techniques have been developed over the past few decades to address the difficulty of imposing appropriate boundary conditions on particular soft tissues during mechanical testing. Two criteria for a successful clamping mechanism are (i) prevention of test specimen slippage, and (ii) prevention of test specimen failure outside the gage region. Herein we present a novel clamping mechanism design developed for the mechanical testing of abdominal wall tissue as an example. This design incorporates pins with serrated clamps to successfully decrease the occurrence of test sample slippage while reducing imposed stress concentrations at the clamping sites. This design was evaluated by performing 40 uniaxial tensile tests on rat abdominal wall muscles using strain rates of 1% per second or 10% per second. Load and displacement data were acquired at the grips. The clamping area on the tissue sample was marked with India ink to track potential slippage of the sample during testing. Ultimate tensile strength and the corresponding stretch were calculated when the maximum load was achieved. With fine-tuning of the torque applied to the clamping grips, the success rate of the tensile tests reached over 90%., Competing Interests: Declaration of competing interest The authors of this paper have no Conflicts of Interest to report., (Copyright © 2019. Published by Elsevier Ltd.)

It is common practice to evaluate the mechanical performance of a scaffold for tissue engineering using concepts from linear elasticity theory (i.e. Young's modulus), or variations thereof, and uniaxial testing data. In some cases the non-linear nature of tissue stress-strain behavior has prompted development of empirical approaches to obtain a more comprehensive description of the observed mechanical behavior. Such approaches constitute improvements over singular stiffness measures but the lack of an appropriate non-linear theoretical foundation renders them somewhat arbitrary and potentially incomplete. Recently, a constitutive model for non-linear tissues was developed based on first principles in physics. The Freed-Rajagopal 1-D Fiber Model incorporates physically meaningful parameters that provide a unique and comprehensive characterization of non-linear tissue behavior for the class of tissues with strain limiting behavior in 1D. The physical interpretation that these parameters provide suggests they may serve as useful design targets for tissue engineering applications. In this study, the Freed-Rajagopal model is employed with conventional uniaxial mechanical testing data obtained from experiments with collagen scaffolds for hernia repair grafts and the healthy native tissue counterpart. Results from the Freed-Rajagopal analysis revealed that tissue-engineered constructs that qualify as "biomimetic" according to linear elasticity theory, or variations thereof, are not truly biomimetic, as they do not mimic the non-linear mechanical behaviors observed in their native tissue counterparts. Most importantly, the Freed-Rajagopal model was easy to employ (it can be done using a standard uniaxial testing system, with minimal additional effort) and revealed specific design improvements that could be targeted to improve the biofidelity of these constructs. A performance comparison with conventional non-linear models (including Fung's 1D Law and a one-dimensionalized version of the Holzapfel, Gasser, Ogden model), was then conducted and revealed the Freed-Rajagopal model produced results that correlated exceptionally well with experimental data and better describes material behavior at low strains as compared to competing models., (Copyright © 2019. Published by Elsevier Ltd.)

Thermally conductive polymer crystals are of both fundamental and practical interest for their high thermal conductivity that exceeds that of many metals. In particular, polyethylene fibers and oriented films with uniaxial thermal conductivity exceeding 50 [Formula: see text] have been reported recently, stimulating interest into the underlying microscopic thermal transport processes. While ab initio calculations have provided insight into microscopic phonon properties for perfect crystals, such properties of actual samples have remained experimentally inaccessible. Here, we report the direct observation of thermal phonons with mean free paths up to 200 nm in semicrystalline polyethylene films using transient grating spectroscopy. Many of the mean free paths substantially exceed the crystalline domain sizes measured using small-angle X-ray scattering, indicating that thermal phonons propagate ballistically within and across the nanocrystalline domains; those transmitting across domain boundaries contribute nearly one-third of the thermal conductivity. Our work provides a direct determination of thermal phonon propagation lengths in molecular solids, yielding insights into the microscopic origins of their high thermal conductivity., Competing Interests: The authors declare no conflict of interest.

The incidence of Alzheimer's disease (AD), which is characterized by progressive cognitive decline that correlates with the spread of tau protein aggregation in the cortical mantle, is strongly age-related. It could be that age predisposes the brain for tau misfolding and supports the propagation of tau pathology. We tested this hypothesis using an experimental setup that allowed for exploration of age-related factors of tau spread and regional vulnerability. We virally expressed human tau locally in entorhinal cortex (EC) neurons of young or old mice and monitored the cell-to-cell tau protein spread by immunolabeling. Old animals showed more tau spreading in the hippocampus and adjacent cortical areas and accumulated more misfolded tau in EC neurons. No misfolding, at any age, was observed in the striatum, a brain region mostly unaffected by tangles. Age and brain region dependent tau spreading and misfolding likely contribute to the profound age-related risk for sporadic AD.

Background: Activation of inflammation pathways in the brain occurs in Alzheimer's disease and may contribute to the accumulation and spread of pathological proteins including tau. The goal of this study was to identify how changes in microglia, a key inflammatory cell type, may contribute to tau protein accumulation and pathology-associated changes in immune and non-immune cell processes such as neuronal degeneration, astrocyte physiology, cytokine expression, and blood vessel morphology., Methods: We used PLX3397 (290 mg/kg), a colony-stimulating factor receptor 1 (CSF1R) inhibitor, to reduce the number of microglia in the brains of a tau-overexpressing mouse model. Mice were fed PLX3397 in chow or a control diet for 3 months beginning at 12 months of age and then were subsequently analyzed for changes in blood vessel morphology by in vivo two-photon microscopy and tissues were collected for biochemistry and histology., Results: PLX3397 reduced microglial numbers by 30% regardless of genotype compared to control diet-treated mice. No change in tau burden, cortical atrophy, blood vessels, or astrocyte activation was detected. All Tg4510 mice were observed to have an increased in "disease-associated" microglial gene expression, but PLX3397 treatment did not reduce expression of these genes. Surprisingly, PLX3397 treatment resulted in upregulation of CD68 and Tgf1β., Conclusions: Manipulating microglial activity may not be an effective strategy to combat tau pathological lesions. Higher doses of PLX3397 may be required or earlier intervention in the disease course. Overall, this indicates a need for a better understanding of specific microglial changes and their relation to the disease process.

Background: The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain.", Methods: One hundred consecutive patients aged ≥18 years who presented with a chief complaint of pain were asked to record pain scores via a paper VAS and digitally via both the laptop computer and mobile phone. Ninety-eight subjects, 51 men (age, 44 ± 16 years) and 47 women (age, 46 ± 15 years), were included. A mixed-model analysis of covariance with the Bonferroni post hoc test was used to detect differences between the paper and digital VAS scores. A Bland-Altman analysis was used to test for instrument agreement between the platforms. The minimal clinically important difference was set at 1.4 cm (14% of total scale length) for detecting clinical relevance between the three VAS platforms. A paired one-tailed Student t -test was used to determine whether differences between the digital and paper measurement platforms exceeded 14% ( P < 0.05)., Results: A significant difference in scores was found between the mobile phone-based (32.9% ± 0.4%) and both the laptop computer- and paper-based platforms (31.0% ± 0.4%, P < 0.01 for both). These differences were not clinically relevant (minimal clinically important difference <1.4 cm). No statistically significant difference was observed between the paper and laptop computer platforms. Measurement agreement was found between the paper- and laptop computer-based platforms (mean difference, 0.0% ± 0.5%; no proportional bias detected) but not between the paper- and mobile phone-based platforms (mean difference, 1.9% ± 0.5%; proportional bias detected)., Conclusion: No clinically relevant difference exists between the traditional paper-based VAS assessment and VAS scores obtained from laptop computer- and mobile phone-based platforms., Competing Interests: Dr. Boutris or an immediate family member is an employee of Zimmer Biomet. Dr. McCulloch or an immediate family member has received research or institutional support from Arthrex and DePuy Synthes; serves as a board member, owner, officer, or committee member of the Journal of Knee Surgery and Orthobullets.com; and is a member of a speakers' bureau or has made paid presentations on behalf of Vericel. Dr. Moreno or an immediate family member has received research or institutional support from 4WEB Medical. Dr. Harris or an immediate family member serves as a board member, owner, officer, or committee member of the American Academy of Orthopaedic Surgeons, the American Orthopaedic Society for Sports Medicine, Arthroscopy, the Arthroscopy Association of North America, and Frontiers In Surgery; has received research or institutional support from DePuy Synthes and Smith & Nephew; serves as a paid consultant to NIA Magellan, Össur, and Smith & Nephew; is a member of a speakers' bureau or has made paid presentations on behalf of Össur and Smith & Nephew; and has received nonincome support (such as equipment or services), commercially derived honoraria, or other non–research-related funding (such as paid travel) from SLACK. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Ms. Delgado, Dr. Lambert, and Mr. Robbins.

Mixed pathology, with both Alzheimer's disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer's disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa , Serpine1 , and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain's microvasculature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Although a variety of fabrication methods have been developed to generate electrospun meshes with gradient properties, no platform has yet to achieve fiber alignment in the direction of the gradient that mimics the native tendon-bone interface. In this study, we present a method combining in-line blending and air-gap electrospinning to address this limitation in the field. A custom collector with synced rotation permitted fiber collection with uniform mesh thickness and periodic copper wires were used to induce fiber alignment. Two poly(ester urethane ureas) with different hard segment contents (BPUR 50, BPUR 10) were used to generate compositional gradient meshes with and without fiber alignment. The compositional gradient across the length of the mesh was characterized using a fluorescent dye and the results indicated a continuous transition from the BPUR 50 to the BPUR 10. As expected, the fiber alignment of the gradient meshes induced a corresponding alignment of adherent cells in static culture. Tensile testing of the sectioned meshes confirmed a graded transition in mechanical properties and an increase in anisotropy with fiber alignment. Finite element modeling was utilized to illustrate the gradient mechanical properties across the full length of the mesh and lay the foundation for future computational development work. Overall, these results indicate that this electrospinning method permits the fabrication of macromolecular gradients in the direction of fiber alignment and demonstrate its potential for use in interfacial tissue engineering., Statement of Significance: The native tendon-bone interface contains a gradient of properties that ensures stability of the joint. Without this transition, failure can occur due to stress concentration at the bone insertion site. Electrospinning is a method commonly used to produce fibrous grafts with gradient properties; however, no current method allows for gradients in the direction of fiber alignment. This work details a novel electrospinning method to produce gradients in the direction of fiber alignment in order to better mimic transitional zones and improve regeneration of the tendon-bone interface. In addition to the biomechanical gradients demonstrated here, this method may also be used to generate gradients of macromolecular, biochemical, and cellular cues with broad potential utility in tissue engineering., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Medicinal leeches (Hirudo verbana) thermoregulate with respect to their sanguivorous feeding behavior. Immediate postprandial preferences are for warmer than their initial acclimation temperature (T a , 21°C, Petersen et al. 2011), while unfed leeches have a lower preferred temperature (T pref , 12.5°C). This may reduce energy expenditure and defer starvation if feeding opportunities are limited. Energetic benefits may have an associated cost if low temperatures reduce mobility and the ability to locate further hosts. These costs could be limited if mobility is unimpaired at low temperatures, or if acclimation can restore locomotor performance to the levels at T a . The transition from T a to the unfed T pref significantly reduced speed and propulsive cycle frequency during swimming, and extension and retraction rates during crawling. Aerobic metabolic rate was also reduced from 0.20±0.03Wkg -1 at T a to 0.10±0.03Wkg -1 at T pref . The Q 10 values of 1.7-2.9 for energetic and swimming parameters indicate a substantial temperature effect, although part of the decline in swimming performance can be attributed to temperature-related changes in water viscosity. 6 weeks at T a resulted in no detectable acclimation in locomotor performance or aerobic metabolism. The energetic savings associated with a lower T pref in unfed leeches effectively doubled the estimated time until depletion of energy reserves. Given that some mobility is still retained at T pref , and that acclimation is in itself costly, the energetic benefits of selecting cooler temperatures between feedings may outweigh the costs associated with reduced locomotor performance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair., Statement of Significance: Due to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE Sheets and Scaffolds) not only showed promising mechanical performance, but also allowed for an efficient neovascularization, resulting in new adipose and muscle tissue formation within the implant, in only 6weeks. In addition, our meshes allowed for the use of the same surgical procedure utilized in clinical practice, with the commercially available grafts. This study represents a significant step in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral hernia repair., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

As nanocrystal (NC) synthesis techniques and device architectures advance, it becomes increasingly apparent that new ways of connecting NCs with each other and their external environment are required to realize their considerable potential. Enhancing inter-NC coupling by thermal annealing has been a long-standing challenge. Conventional thermal annealing approaches are limited by the challenge of annealing the NC at sufficiently high temperatures to remove surface-bound ligands while at the same time limiting the thermal budget to prevent large-scale aggregation. Here we investigate nonequilibrium laser annealing of NC thin films that enables separation of the kinetic and thermodynamic aspects of nanocrystal fusion. We show that laser annealing of NC assemblies on nano- to microsecond time scales can transform initially isolated NCs in a thin film into an interconnected structure in which proximate dots "just touch". We investigate both pulsed laser annealing and laser spike annealing and show that both annealing methods can produce "confined-but-connected" nanocrystal films. We develop a thermal transport model to rationalize the differences in resulting film morphologies. Finally we show that the insights gained from study of nanocrystal mono- and bilayers can be extended to three-dimensional NC films. The basic processing-structure-property relationships established in this work provide guidance to future advances in creating functional thin films in which constituent NCs can purposefully interact.

Background: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast with balloon-based accelerated partial breast irradiation (APBI) to determine the efficacy of this treatment approach in this group of patients., Materials and Methods: A total of 126 cases of DCIS seen and treated with APBI using balloon-based brachytherapy constitute the study population. The median age at diagnosis was 59 years (range, 37-82) with 21% younger than age 50. Nuclear grade distribution was 52.5, 41.4, and 6.1% high, intermediate and low, respectively. Of these patients, 86% had estrogen receptor positive DCIS. The median tumor size was 6 mm (range, 1-26). Margins of excision were negative in 98.4% of patients. All patients were treated with 34 Gy in 10 fractions using either the MammoSite™ or Contura™ breast brachytherapy catheter. A total of 87 patients (73.1%) were placed on adjuvant tamoxifen or arimedex., Results: With a median follow-up of 24 months (range, 0.7-73.9), three (2.4%) ipsilateral breast tumor recurrences (IBTRs) developed for a 2-year actuarial rate of 0.81%. Recurrences developed 4.8, 24.7, and 24.9 months after treatment. On univariate analysis, no variable was associated with IBTR. A subset analysis of the first 50 consecutive patients treated was also performed. With a median follow-up of 40 months (range, 15.6-73.9), one IBTR developed for a 3-year actuarial rate of 2.15%., Conclusions: Early results in patients with DCIS treated with APBI using balloon-based brachytherapy produced results similar to those with invasive cancer treated with APBI or DCIS treated with whole breast irradiation.

We reviewed our surgical experience with the Contura Multi Lumen Balloon breast brachytherapy catheter used to deliver accelerated partial breast irradiation and determined short-term treatment efficacy, cosmesis, and toxicity. Forty-six patients undergoing breast conserving therapy, including the use of Contura catheter, were analyzed. Thirty-four Gray were delivered in 10 fractions. Fourteen patients had stage 0, 24 had stage I, and 8 had stage II breast cancer. Catheters were placed with a closed cavity technique. Median minimum skin spacing was 10 mm (range, 2-18 mm). Median maximum skin doses were 99.7 per cent of the prescription dose. Nine patients were treated with a skin spacing < or = 5 mm (2 patients with 2 mm skin spacing). The percentage of patients with excellent/good cosmesis at 6 (n = 26) and 12 (n = 13) months was 100 per cent, respectively. Patient tolerance was assessed on a scale of 0-10 (0 = no pain, 10 = requiring narcotic analgesics). Pain was graded < or = 3 in 98 per cent of patients at catheter insertion and 84 per cent at catheter removal. Four breast infections (8.8%) and one symptomatic seroma developed. Adjuvant accelerated partial breast irradiation using the Contura Multi Lumen Balloon exhibited similar toxicities to standard single lumen, single dwell balloon brachytherapy with improvements in dosimetric capabilities allowing the treatment of patients with skin spacing < or = 5 mm.

We report the first case of transvenous removal of a peripheral inserted central catheter (PICC) fragment embolized to a peripheral vein in a 32-week gestational age 1450 g infant. The technical aspect of this alternative method to surgery is discussed.

Cold insoluble globulin (fibronectin, alpha 2-surface binding glycoprotein) is a naturally occurring substance necessary for optimal stimulation of the reticuloendothelial system. While this globulin depends on macrophages as the effector cells for its opsonic function, as is true of both antibody and complement, it is neither part of nor dependent on these systems for its opsonic activity. A relatively simple bioassay developed at the Medical College of Georgia substantiated that cold insoluble globulin is severely depleted in sepsis. Cryoprecipitate, properly processed and stored, is an exogenous source of cold insoluble globulin. Infused into septic patients 10 units thawed at 2 degrees C and reconstituted to 250 ml with saline solution can temporarily restore cold insoluble globulin levels and enhance activity of the reticuloendothelial system. Proper current use dictates measurement of cold insoluble globulin levels in the infusate as well as levels in the patient and the clinical response to infusion. Our bioassay and a septic patient's response to infusion of cold insoluble globulin are reported herein.

Various transition metal complexes containing nitroimidazoles as ligands have been shown to act as radiosensitizers of hypoxic cells in vitro. Sensitization by cis-Pt(II)Cl2 (nitroimidazole)2 complexes is no greater than that which can be demonstrated by the free nitroimidazole ligand alone. These results differ from those previously described for the compound FLAP where an ER of 2.4 was obtained at a concentration of 50 microM. We report that, even using the same treatment technique, the maximum ER that can be achieved is 1.2. Further, the sensitizing efficiency of FLAP cannot be improved when cells are kept in contact with the compound for 12 hours in air prior to deoxygenation and irradiation. In contrast, Rh(II) complexes show much greater sensitization than can be obtained with the free ligand and these compounds are in turn more efficient sensitizers than the comparable Pt(II) complexes.

Levels of cold insoluble globulin (CIG), also called opsonic alpha2 surface-binding glycoprotein, humoral recognition factor, and fibronectin, are depressed as a result of major trauma. This protein normally promotes the phagocytosis and removal of abnormal particles and bacteria by cells of the recticuloendothelial system. Although CIG depends on macrophages as the effector cells for its opsonic function as is true of both antibody and complement, CIG is neither part of nor dependent on these systems for its opsonic activity. Using a new, rapid bioassay, we have demonstrated that in humans subjected to operative trauma, circulating CIG levels are considerably depressed in the early hours after operation and return to normal within 24 hours. The observed decreases in titer varied in extent, time of onset, and duration. Continuing study is designed to determine potential correlation between initial levels of CIG, decreases in titer resulting from operation, and the incidence of postoperative infection.