Search

Activation of calpain1 (CPN1) contributes to mitochondrial dysfunction during cardiac ischemia (ISC) - reperfusion (REP). Blockade of electron transport using amobarbital (AMO) protects mitochondria during ISC-REP, indicating that the electron transport chain (ETC) is a key source of mitochondrial injury. We asked if AMO treatment can decrease CPN1 activation as a potential mechanism of mitochondrial protection during ISC-REP. Buffer-perfused adult rat hearts underwent 25 min global ISC and 30 min REP. AMO (2.5 mM) or vehicle was administered for 1 min before ISC to block electron flow in the ETC. Hearts in the time control group were untreated and buffer perfused without ISC. Hearts were collected at the end of perfusion and used for mitochondrial isolation. ISC-REP increased both the cleavage of spectrin (indicating cytosolic CPN1 activation) in cytosol and the truncation of AIF (apoptosis inducing factor, indicating mitochondrial CPN1 activation) in subsarcolemmal mitochondria compared to time control. Thus, ISC-REP activated both cytosolic and mitochondrial CPN1. AMO treatment prevented the cleavage of spectrin and AIF during ISC-REP, suggesting that the transient blockade of electron transport during ISC decreases CPN1 activation. AMO treatment decreased the activation of PARP [poly(ADP-ribose) polymerase] downstream of AIF that triggers caspase-independent apoptosis. AMO treatment also decreased the release of cytochrome c from mitochondria during ISC-REP that prevented caspase 3 activation. These results support that the damaged ETC activates CPN1 in cytosol and mitochondria during ISC-REP, likely via calcium overload and oxidative stress. Thus, AMO treatment to mitigate mitochondrial-driven cardiac injury can decrease both caspase-dependent and caspase-independent programmed cell death during ISC-REP.

Here, we describe the full-length genome sequence of a novel potyvirus, tentatively named “Miscanthus sinensis mosaic virus” (MsiMV), isolated from Miscanthus sinensis (silver grass) held in a post-entry quarantine facility after being imported into Western Australia, Australia. The MsiMV genome is 9604 nucleotides (nt) in length, encoding a 3071-amino-acid (aa) polyprotein with conserved sequence motifs. The MsiMV genome is most closely related to that of sorghum mosaic virus (SrMV), with 74% nt and 78.5% aa sequence identity to the SrMV polyprotein region. Phylogenetic analysis based on the polyprotein grouped MsiMV with SrMV, sugarcane mosaic virus (SCMV), and maize dwarf mosaic virus (MDMV). This is the first report of a novel monopartite ssRNA virus in Miscanthus sinensis related to members of the genus Potyvirus in the family Potyviridae.

Background: Fournier’s gangrene (FG) is a fatal condition that often leads to death if not treated properly. To this date, there are no data regarding FG in Indonesia. Objective: This study aims to investigate the characteristics of patients with FG.Methods: A cross-sectional study design was used to evaluate the medical records of patients admitted to Cipto Mangunkusumo Hospital between January 2012 and December 2017.Results: The median age of the subjects were 51 (2-81) years. All of the subjects were male and presented with scrotal pain. The scrotal abscess was found in 38 (88.4%) cases. Type II diabetes was found in 10 (23.3%) subjects. E. coli was the most dominant causative agent in 28 (65.1%) cases. Meropenem was administered in 16 (37.2%) subjects, and 16 (37.2%) subjects had antibiotics administered for ≤7 days. Conclusion: Although the mortality rate has decreased, those with FG tend to have a long hospital stay, which implies a high risk of complications. All males presenting with scrotal pain should be suspected of FG. Further studies on long-term hospitalisation complications in those with FG are required.

In this study 163 complete whole-genome sequences of the emerging pathogen grapevine red blotch virus (GRBV; genus Grablovirus, family Geminiviridae) were used to reconstruct phylogenies using Bayesian analyses on time-tipped (heterochronous) data. Using different combinations of priors, Bayes factors identified heterochronous datasets (3×200 million chains) generated from strict clock and exponential tree priors as being the most robust. Substitution rates of 3.2×10−5 subsitutions per site per year (95% HPD 4.3–2.1×10−5) across the whole of the GRBV genome were estimated, suggesting ancestral GRBV diverged from ancestral wild Vitis latent virus 1 around 9 000 years ago, well before the first documented arrival of Vitis vinifera in North America. Whole-genome analysis of GRBV isolates in a single infected field-grown grapevine across 12 years identified 12 single nucleotide polymorphisms none of which were fixed substitutions: an observation not discordant with the in silico estimate. The substitution rate estimated here is lower than those estimated for other geminiviruses and is the first for a woody-host-infecting geminivirus.

Introduction: The concept of voiding patterns in neonates had not been completely understood. The voiding pattern in neonates was physiologically different from that in older children. The brain's development affects voiding patterns in frequency, bladder volume, and post-void residual bladder volume, as the child keeps growing. This study aims to understand the physiological neonates' voiding system in Indonesian newborns.Materials and methods: We evaluate ten normal-born and 12 perinatology-hospitalized aterm neonates without anatomical or physiological urologic abnormalities at RSUP Haji Adam Malik from October to November 2019. We used an observational study, assessing the voiding physiology in newborns, including voiding frequency and urine volume. Infants with a history of urinary tract infection or present bacteriuria confirmed by urine culture were excluded. Voiding volume, frequency, bladder capacity, and residual volume were measured. Results: We collected a total of 22 patients, with 12 patients were perinatology-hospitalized and ten patients were healthy neonates with ten subjects were male, and 12 subjects were female. There was no correlation between voiding frequency and total voiding volume with perinatology-hospitalized, healthy neonates, and sex. (p>0.05). Independent T-test was performed with a p-value for volume, frequency, bladder capacity, and residual volume of 0.225, 0.112, 0.031, and 0.663. We got a significant difference in bladder capacity between healthy neonates and perinatology-hospitalized. No significant differences were noted in other variables. Pearson correlation analysis was performed to determine the correlation between total voiding volume and age of gestation, body weight, length, head circumference, abdominal circumference, and chest circumference. The correlation coefficients were 0.772, 0.869, 0.623, 0.698, 0.079, 0.523 in order, with significant p-value in the age of gestation, body weight, length, head circumference, and chest circumference. There were correlations between total voiding volume and age of gestation, body weight, length, head circumference, and chest circumference. Conclusion: In conclusion, we found there was a significant difference in bladder capacity between healthy neonates and perinatology-hospitalized.

p53 is a tumor suppressor protein with a very low content in the basal condition, but the content rapidly rises during stress conditions including ischemia-reperfusion. An increase in p53 content increases cardiac injury during ischemia-reperfusion. Since mitochondrial damage plays a key role in cardiac injury during ischemia-reperfusion, we asked if genetic ablation of p53 decreases cardiac injury by protecting mitochondria. Isolated, perfused hearts from cardiac specific p53 deletion or wild type underwent 25 min global ischemia at 37 °C and 60 min reperfusion. At the end of reperfusion, hearts were harvested for infarct size measurement. In separate groups, cardiac mitochondria were isolated at 30 min reperfusion. Time control hearts were buffer-perfused without ischemia. Compared to wild type, deletion of p53 improved cardiac functional recovery and decreased infarct size following ischemia-reperfusion. Oxidative phosphorylation was improved in p53 deletion mitochondria following ischemia-reperfusion compared to wild type. The net release of ROS generation from wild type but not in p53 deletion mitochondria was increased following ischemia-reperfusion. Peroxiredoxin 3 (PRDX 3) content was higher in p53 deletion than that in wild type, indicating that p53 deletion increases a key antioxidant. Ischemia-reperfusion led to increased spectrin cleavage (a marker of cytosolic calpain1 activation) in wild type but not in p53 deletion mice. Ischemia-reperfusion increased the truncation of mature AIF (apoptosis inducing factor, an indicator of mitochondrial calpain1 activation) in wild type but not in p53 deletion mice. The loss of cytochrome c from mitochondria was also decreased in p53 deletion following ischemia-reperfusion. Bcl-2 content was decreased in wild type but not in p53 deletion following reperfusion, suggesting that depletion of bcl-2 contributes to permeabilization of the mitochondrial outer membrane. Thus, deletion of p53 decreases cardiac injury by protecting mitochondria through attenuation of oxidative stress and calpain activation during ischemia-reperfusion.

In Conway’s game, Sylver Coinage, the set of legal plays forms the complement of a numerical semigroup after a finite number of turns. Our goal is to show how the tools and techniques of numerical ...

Aging chronically increases endoplasmic reticulum (ER) stress that contributes to mitochondrial dysfunction. Activation of calpain 1 (CPN1) impairs mitochondrial function during acute ER stress. We proposed that aging-induced ER stress led to mitochondrial dysfunction by activating CPN1. We posit that attenuation of the ER stress or direct inhibition of CPN1 in aged hearts can decrease cardiac injury during ischemia-reperfusion by improving mitochondrial function. Male young (3 mo) and aged mice (24 mo) were used in the present study, and 4-phenylbutyrate (4-PBA) was used to decrease the ER stress in aged mice. Subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) were isolated. Chronic 4-PBA treatment for 2 wk decreased CPN1 activation as shown by the decreased cleavage of spectrin in cytosol and apoptosis inducing factor (AIF) and the α1 subunit of pyruvate dehydrogenase (PDH) in mitochondria. Treatment improved oxidative phosphorylation in 24-mo-old SSM and IFM at baseline compared with vehicle. When 4-PBA-treated 24-mo-old hearts were subjected to ischemia-reperfusion, infarct size was decreased. These results support that attenuation of the ER stress decreased cardiac injury in aged hearts by improving mitochondrial function before ischemia. To challenge the role of CPN1 as an effector of the ER stress, aged mice were treated with MDL-28170 (MDL, an inhibitor of calpain 1). MDL treatment improved mitochondrial function in aged SSM and IFM. MDL-treated 24-mo-old hearts sustained less cardiac injury following ischemia-reperfusion. These results support that age-induced ER stress augments cardiac injury during ischemia-reperfusion by impairing mitochondrial function through activation of CPN1.

Here, we describe the full-length genome sequence of a novel potyvirus, tentatively named "Miscanthus sinensis mosaic virus" (MsiMV), isolated from Miscanthus sinensis (silver grass) held in a post-entry quarantine facility after being imported into Western Australia, Australia. The MsiMV genome is 9604 nucleotides (nt) in length, encoding a 3071-amino-acid (aa) polyprotein with conserved sequence motifs. The MsiMV genome is most closely related to that of sorghum mosaic virus (SrMV), with 74% nt and 78.5% aa sequence identity to the SrMV polyprotein region. Phylogenetic analysis based on the polyprotein grouped MsiMV with SrMV, sugarcane mosaic virus (SCMV), and maize dwarf mosaic virus (MDMV). This is the first report of a novel monopartite ssRNA virus in Miscanthus sinensis related to members of the genus Potyvirus in the family Potyviridae.

The paper investigates matrix-free high-order implementation of finite element discretization with p-multigrid preconditioning for the compressible Neo-Hookean hyperelasticity problem at finite strain on unstructured 3D meshes in parallel. We consider two formulations for the matrix-free action of the Jacobian in Neo-Hookean hyperelasticity: (i) working in the reference configuration to define the second Piola-Kirchhoff tensor as a function of the Green-Lagrange strain S(E) (or equivalently, the right Cauchy-Green tensor C = I+2E), and (ii) working in the current configuration to define the Kirchhoff stress in terms of the left Cauchy-Green tensor τ(b). The proposed efficient algorithm utilizes the Portable, Extensible Toolkit for Scientific Computation (PETSc), along with the libCEED library for efficient compiler optimized tensor-product-basis computation to demonstrate an efficient nonlinear solution algorithm. We utilize p-multigrid preconditioning on the high-order problem with algebraic multigrid (AMG) on the assembled linear Q1 coarse grid operator. In contrast to classical geometric multigrid, also known as h-multigrid, each level in p-multigrid is related to a different approximation polynomial order p, instead of the element size h. A Chebyshev polynomial smoother is used on each multigrid level. AMG is then applied to the assembled Q1 (trilinear hexahedral elements), which allows low storage that can be efficiently used to accelerate convergence to a solution. For the compressible Neo-Hookean hyperelastic constitutive model we exploit the stored energy density function to compute the stored elastic energy density of the Neo-Hookean material as it relates to the deformation gradient. Based on our formulation, we consider four different algorithms each with different storage strategies. Algorithms 1 and 3 are implemented in the reference and current configurations respectively and store ∇Xξ, det(∇ξX), and ∇Xu. Algorithm 2 in the reference configuration stores, ∇Xξ, det(∇ξX), ∇Xu, C−1, and λ log (J). Algorithm 4, in the current configuration, stores det(∇ξX), ∇xξ, τ, and μ – λ log(J). x refers to the current coordinates, X to the reference coordinates, and ξ to the natural coordinates. We perform 3D bending simulations of a tube composed of aluminum (modulus of elasticity E = 69 GPa, Poisson’s ratio v = 0.3) using unstructured meshes and polynomials of order p = 1 through p = 4 under mesh refinement. We explore accuracy-time-cost tradeoffs for the prediction of strain energy across the range of polynomial degrees and Jacobian representations. In all cases, Algorithm 4 using the current configuration formulation outperforms the other three algorithms and requires less storage. Similar simulations for large deformation compressible Neo-Hookean hyperelasticity as applied to the same aluminum material are conducted with ABAQUS, a commercial finite element software package which is a state-of-the-art engineering software package for finite element simulations involving large deformation. The best results from the proposed implementations and ABAQUS are compared in the case of p = 2 on an Intel system with @2.4 GHz and 128 GB RAM. Algorithm 4 outperforms ABAQUS for polynomial degree p = 2.

A novel virus, tentatively named "sweetbriar rose curly-top associated virus" (SRCTaV), was identified in sweetbriar rose (Rosa rubiginosa) using high-throughput sequencing. The complete genome sequence of SRCTaV was determined and characterized. Phylogenetic analysis revealed that SRCTaV is closely related to members of the genus Waikavirus.

Efficient exploitation of exascale architectures requires rethinking of the numerical algorithms used in many large-scale applications. These architectures favor algorithms that expose ultra fine-grain parallelism and maximize the ratio of floating point operations to energy intensive data movement. One of the few viable approaches to achieve high efficiency in the area of PDE discretizations on unstructured grids is to use matrix-free/partially-assembled high-order finite element methods, since these methods can increase the accuracy and/or lower the computational time due to reduced data motion. In this paper we provide an overview of the research and development activities in the Center for Efficient Exascale Discretizations (CEED), a co-design center in the Exascale Computing Project that is focused on the development of next-generation discretization software and algorithms to enable a wide range of finite element applications to run efficiently on future hardware. CEED is a research partnership involving more than 30 computational scientists from two US national labs and five universities, including members of the Nek5000, MFEM, MAGMA and PETSc projects. We discuss the CEED co-design activities based on targeted benchmarks, miniapps and discretization libraries and our work on performance optimizations for large-scale GPU architectures. We also provide a broad overview of research and development activities in areas such as unstructured adaptive mesh refinement algorithms, matrix-free linear solvers, high-order data visualization, and list examples of collaborations with several ECP and external applications., 22 pages, 18 figures

Objectives: Because of its multifaceted cardioprotective effects, remote ischemic pre-conditioning (RIPC) was examined as a strategy to attenuate doxorubicin (DOX) cardiotoxicity. Background: The use of DOX is limited by dose-dependent cardiotoxicity and heart failure. Oxidative stress, mitochondrial dysfunction, inflammation, and autophagy modulation have been proposed as mediators of DOX cardiotoxicity. Methods: After baseline echocardiography, adult male CD1 mice were randomized to either sham or RIPC protocol (3 cycles of 5 min femoral artery occlusion followed by 5 min reperfusion) 1 h before receiving DOX (20 mg/kg, intraperitoneal). The mice were observed primarily for survival over 85 days (86 mice). An additional cohort of 50 mice was randomized to either sham or RIPC 1 h before DOX treatment and was followed for 25 days, at which time cardiac fibrosis, apoptosis, and mitochondrial oxidative phosphorylation were assessed, as well as the expression profiles of apoptosis and autophagy markers. Results: Survival was significantly improved in the RIPC cohort compared with the sham cohort (p = 0.007). DOX-induced cardiac fibrosis and apoptosis were significantly attenuated with RIPC compared with sham (p < 0.05 and p < 0.001, respectively). Although no mitochondrial dysfunction was detected at 25 days, there was a significant increase in autophagy markers with DOX that was attenuated with RIPC. Moreover, DOX caused a 49% decline in cardiac BCL2/BAX expression, which was restored with RIPC (p < 0.05 vs. DOX). DOX also resulted in a 17% reduction in left ventricular mass at 25 days, which was prevented with RIPC (p < 0.01), despite the lack of significant changes in left ventricular ejection fraction. Conclusions: Our preclinical results suggested that RIPC before DOX administration might be a promising approach for attenuating DOX cardiotoxicity.

Activation of calpain 1 (CPN1) and calpain 2 (CPN2) contributes to cardiac injury during ischemia (ISC) and reperfusion (REP). Complex I activity is decreased in heart mitochondria following ISC-REP. CPN1 and CPN2 are ubiquitous calpains that exist in both cytosol (cs)-CPN1 and 2 and mitochondria (mit)-CPN1 and 2. Recent work shows that the complex I subunit (NDUFS7) is a potential substrate of the mit-CPN1. We asked whether ISC-REP led to decreased complex I activity via proteolysis of the NDUFS7 subunit via activation of mit-CPN1 and -2. Activation of cs-CPN1 and -2 decreases mitophagy in hepatocytes following ISC-REP. We asked whether activation of cs-CPN1 and -2 impaired mitophagy in the heart following ISC-REP. Buffer-perfused rat hearts underwent 25 min of global ISC and 30 min of REP. MDL-28170 (MDL; 10 µM) was used to inhibit CPN1 and -2. Cytosol, subsarcolemmal mitochondria (SSM), and interfibrillar mitochondria (IFM) were isolated at the end of heart perfusion. Cardiac ISC-REP led to decreased complex I activity with a decrease in the content of NDUFS7 in both SSM and IFM. ISC-REP also resulted in a decrease in cytosolic beclin-1 content, a key component of the autophagy pathway required to form autophagosomes. MDL treatment protected the contents of cytosolic beclin-1 and mitochondrial NDUFS7 in hearts following ISC-REP. These results support that activation of both cytosolic and mitochondrial calpains impairs mitochondria during cardiac ISC-REP. Mitochondria-localized calpains impair complex I via cleavage of a key subunit. Activation of cytosolic calpains contributes to mitochondrial dysfunction by impairing removal of the impaired mitochondria through depletion of a key component of the mitophagy process.

Prior to 1994, the media operated in an environment that can best be described as ‘suppressed’. Diversity of thoughts, views and opinions on media platforms were non-existent as the regime, at the time, ruled with an iron-fist. A variety of print media outlets sought to reflect reality, but it was a steady struggle especially for those with meagre resources, and exacerbated by the constant clampdowns. The state-run broadcaster, if anything, entrenched discriminatory principles and practices. Given our precarious past, the birth of democracy proved to be the perfect panacea for a promising pathway for the media fraternity. Transformation, in more ways than one, permeated the sector. Reflections of the South African Media: 1994-2019 is a compilation by authors who have peculiar insight of and excelled in the different areas of the fast-developing industry in the first 25 years of South Africa’s democracy. And they are no ordinary authors. Every chapter contributed came from women and men who had, through the years, a direct link with ML Sultan Technikon, Technikon Natal, Durban Institute of Technology (DIT) or Durban University of Technology (DUT) * either as a student, lecturer, visiting professor, speaker or associate. Compiling and editing this book has been an incredibly invigorating experience. It was never in doubt whose image will adorn the cover of the book, so it was beautifully uplifting that many authors, not knowing my choice, gave Nelson Mandela due recognition. My brief to the authors was simple: let me have your personal lookback in your own style on the topic that you are most comfortable with. All of them stepped up to the plate, and the vast array of content in the book bares strong testimony. A section titled Journeys in Journalism encapsulates input from alumni of DUT Journalism – they were afforded free reign to trace the territory they traversed. I’m indebted to each and every contributor for generously volunteering their precious time and talent to the book. They were simply magnificent. It has to be said that this publication far exceeded my expectations as it, initially, was a humble idea to celebrate 25 years of the media industry with a handful of contributions. Little did I realise that my desk will be flooded with 40 pieces of excellence and a Foreword penned by the brilliant Jeremy Thompson. My eternal gratitude must also be extended to the small team of assistants for understanding my vision upfront and rallying remarkably throughout. Once you’ve enjoyed the read, I invite you to share Reflections of the South African Media: 1994-2019 with whoever you believe can benefit from its rich and diverse content!

We examine a residual and matrix-free Jacobian formulation of compressible and nearly incompressible (v → 0.5) displacement-only linear isotropic elasticity with high-order hexahedral finite elements. A matrix-free p-multigrid method is combined with algebraic multigrid on the assembled sparse coarse grid matrix to provide an effective preconditioner. The software is verified with the method of manufactured solutions. We explore convergence to a predetermined L2 error of 10-4, 10-5 and 10-6 for the compressible case and 10-4, 10-5 for the nearly-incompressible cases, as the Poisson's ratio approaches 0.5, based upon grid resolution and polynomial order. We compare our results against results obtained from C3D20H mixed/hybrid element available in the commercial finite element software ABAQUS that is quadratic in displacement and linear in pressure. We determine, for the same problem size, that our matrix-free approach for displacement-only implementation is faster and more efficient for quadratic elements compared to the C3D20H element from ABAQUS that is specially designed to handle nearly-incompressible and incompressible elasticity problems. However, as we approach the near incompressibility limit, the number of Conjugate Gradient iterations required to achieve the desired solution increases significantly. &nbsp

Soft materials such as rubber, elastomers, and soft biological tissues mechanically deform at large strain isochorically for all time, or during their initial transient (when a pore fluid, typically incompressible such as water, does not have time to flow out of the deforming polymer or soft tissue porous skeleton). Simulating these large isochoric deformations computationally, such as with the Finite Element Method (FEM), requires higher order (typically quadratic) interpolation functions and/or enhancements through hybrid/mixed methods to maintain stability. Lower order (linear) finite elements with hybrid/mixed formulation may not perform stably for all mechanical loading scenarios involving large isochoric deformations, whereas quadratic finite elements with or without hybrid/mixed formulation typically perform stably, especially when large bending or folding deformations are being simulated. For topology-optimization design of soft robotics, for instance, the FEM solid mechanics solver must run efficiently and stably. Stability is ensured by the higher order finite element formulation (with possible enhancement), but efficiency for higher order FEM remains a challenge. Thus, this paper addresses efficiency from the perspective of computer science algorithms and programming. The proposed efficient algorithm utilizes the Portable, Extensible Toolkit for Scientific Computation (PETSc), along with the libCEED library for efficient compiler optimized tensor-product-basis computation to demonstrate an efficient nonlinear solution algorithm. For preconditioning, a scalable p-multigrid method is presented whereby a hierarchy of levels is constructed. In contrast to classical geometric multigrid, also known as h-multigrid, each level in p-multigrid is related to a different approximation polynomial order, p, instead of the element size, h. A Chebyshev polynomial smoother is used on each multigrid level. Algebraic MultiGrid (AMG) is then applied to the assembled Q1 (linear) coarse mesh on the nodes of the quadratic Q2 (quadratic) mesh. This allows low storage that can be efficiently used to accelerate the convergence to solution. For a Neo-Hookean hyperelastic problem, we examine a residual and matrix-free Jacobian formulation of a tri-quadratic hexahedral finite element with enhancement. Efficiency estimates on AVX-2 architecture based on CPU time are provided as a comparison to similar simulation (and mesh) of isochoric large deformation hyperelasticity as applied to soft materials conducted with the commercially-available FEM software program ABAQUS. The particular problem in consideration is the simulation of an assistive device in the form of finger-bending in 3D.

Aging impairs mitochondrial function that leads to greater cardiac injury during ischemia and reperfusion. Cardiac endoplasm reticulum (ER) stress increases with age and contributes to mitochondrial dysfunction. Metformin is an anti-diabetic drug that protects cardiac mitochondria during acute ER stress. We hypothesized that metformin treatment would improve preexisting mitochondrial dysfunction in aged hearts by attenuating ER stress, followed by a decrease in cardiac injury during subsequent ischemia and reperfusion. Male young (3 mo.) and aged mice (24 mo.) received metformin (300 mg/kg/day) dissolved in drinking water with sucrose (0.2 g/100 ml) as sweetener for two weeks versus sucrose vehicle alone. Cytosol, subsarcolemmal (SSM), and interfibrillar mitochondria (IFM) were isolated. In separate groups, cardioprotection was evaluated using ex vivo isolated heart perfusion with 25 min. global ischemia and 60 min. reperfusion. Infarct size was measured. The contents of CHOP and cleaved ATF6 were decreased in metformin-treated 24 mo. mice compared to vehicle, supporting a decrease in ER stress. Metformin treatment improved OXPHOS in IFM in 24 mo. using a complex I substrate. Metformin treatment decreased infarct size following ischemia-reperfusion. Thus, metformin feeding decreased cardiac injury in aged mice during ischemia-reperfusion by improving pre-ischemic mitochondrial function via inhibition of ER stress.

Aging impairs the mitochondrial electron transport chain (ETC), especially in interfibrillar mitochondria (IFM). Mitochondria are in close contact with the endoplasmic reticulum (ER). Induction of ER stress leads to ETC injury in adult heart mitochondria. We asked if ER stress contributes to the mitochondrial dysfunction during aging. Subsarcolemmal mitochondria (SSM) and IFM were isolated from 3, 18, and 24 mo. C57Bl/6 mouse hearts. ER stress progressively increased with age, especially in 24 mo. mice that manifest mitochondrial dysfunction. OXPHOS was decreased in 24 mo. IFM oxidizing complex I and complex IV substrates. Proteomic analysis showed that the content of multiple complex I subunits was decreased in IFM from 24 mo. hearts, but remained unchanged in in 18 mo. IFM without a decrease in OXPHOS. Feeding 24 mo. old mice with 4-phenylbutyrate (4-PBA) for two weeks attenuated the ER stress and improved mitochondrial function. These results indicate that ER stress contributes to the mitochondrial dysfunction in aged hearts. Attenuation of ER stress is a potential approach to improve mitochondrial function in aged hearts.

Highway programmes typically focus on reducing vehicle collisions with large mammals because of economic or safety reasons, while overlooking the millions of birds that die annually from traffic. We studied wildlife–vehicle collisions along an interstate highway in southern Idaho, USA, with among the highest reported rates of American Barn Owl Tyto furcata road mortality. Carcass data from systematic and ad hoc surveys conducted in 2004–2006 and 2013–2015 were used to explore the extent to which spatial, road geometric and biotic factors explained Barn Owl–vehicle collisions. Barn Owls outnumbered all other identified vertebrate species of roadkill and represented > 25% of individuals and 73.6% of road‐killed birds. At a 1‐km highway segment scale, the number of dead Barn Owls decreased with increasing numbers of human structures, cumulative length of secondary roads near the highway and width of the highway median. The number of dead Barn Owls increased with higher commercial average annual daily traffic (CAADT), small mammal abundance index and grass rather than shrubs in the roadside verge. The small mammal abundance index was also greater in roadsides with grass vs. mixed shrubs, suggesting that Barn Owls may be attracted to grassy portions of the highway with more abundant small mammals for hunting prey. When assessed at a 3‐km highway segment scale, the number of dead Barn Owls again increased, with higher CAADT as well as with greater numbers of dairy farms. At a 5‐km scale, the number of dead Barn Owls increased with a greater percentage of cropland near the highway. Although human conversion of the environment from natural shrub‐steppe to irrigated agriculture in this region of Idaho has probably enhanced habitat for Barns Owls, it simultaneously has increased risk for owl–vehicle collisions where an interstate highway traverses the altered landscape. We review some approaches for highway mitigation and suggest that reducing wildlife–vehicle collisions involving Barn Owls may contribute to the persistence of this species.

Objectives The management of closed diaphyseal humerus fractures in the polytrauma patient varies widely. The aim of this study was to compare outcomes of operative and nonoperative management in this patient population. Design Single-center, retrospective cohort analysis. Setting Urban, Level 1 trauma center. Patients Seventy-one patients with closed diaphyseal humerus fractures, and Injury Severity Score (ISS) of ≥17, treated between 2006 and 2011 were identified. Intervention Patients were treated operatively versus nonoperatively with a functional brace by surgeon preference. Main outcomes Primary outcome was union. Secondary outcomes included time to union, time to release to weightbearing, and complications other than nonunion. Results There was no statistical difference between age, Injury Severity Score, or fracture type between the 2 cohorts. There was a statistically higher incidence of associated orthopaedic injury, and more specifically, lower extremity injury in the group treated with operative intervention. There was no difference in union rates (95% operative, 94% nonoperative), time to union (17 weeks operative, 15 weeks nonoperative), or complication rates between the 2 groups. Time to release to weightbearing was 3 weeks shorter in the operative group (9.3 weeks operative, 12.8 weeks nonoperative). Conclusions Polytrauma patients with closed diaphyseal humerus fractures can be treated successfully with equivalent union rates, time to union, and complication rates when selected for conservative management techniques. The decision to undertake operative management of closed diaphyseal humerus fractures in the polytraumatized patient is multifaceted and should consider patient expectations, demographics, injury profile, and ambulatory status. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.