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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.

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 ...

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.

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.

Objective To discuss the consideration of performing radical cystectomy for rhabdomyosarcoma in children during the COVID-19 pandemic in the urology department of Adam Malik Hospital, Medan. Introduction Rhabdomyosarcoma is a rare malignancy that develops from primitive mesenchymal stem cells. The gold standard for the treatment of rhabdomyosarcoma is radical cystectomy. However, during the COVID-19 pandemic, radical cystectomy becomes a concern due to the risk of virus transmission. This article reported a patient who underwent radical cystectomy during the COVID-19 pandemic. Case presentation A five-year-old female child was admitted to the hospital with chief complaints of bloody urine 1 month before admission. A month before hospital admission, the patient had pain during urination and was treated with radical cystectomy with Abol-Enein pouch modification. Result After the surgery, the patient was able to urinate without any disturbance. Hematuria was not found. There was no complaint related to stricture of the ureter after the surgery. Conclusion In our center, radical cystectomy could be performed in child with bladder rhabdomyosarcoma during COVID-19 pandemic. The procedure is considered a high priority therapy in most regions during COVID-19 pandemic. Abol-Enein technique after radical cystectomy resulted in improvement of symptom with no reported complication in our case.

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.

Background Duchenne muscular dystrophy (DMD) is the most frequently inherited human myopathy and represents the most devastating type of muscular dystrophy. This progressive disease is caused by X-...

Severity of cardiovascular disease increases markedly in elderly patients. In addition, many therapeutic strategies that decrease cardiac injury in adult patients are invalid in elderly patients. Thus, it is a challenge to protect the aged heart in the context of underlying chronic or acute cardiac diseases including ischemia-reperfusion injury. The cause(s) of this age-related increased damage remain unknown. Aging impairs the function of the mitochondrial electron transport chain (ETC), leading to decreased energy production and increased oxidative stress due to generation of reactive oxygen species (ROS). Additionally, ROS-induced oxidative stress can increase cardiac injury during ischemia-reperfusion by potentiating mitochondrial permeability transition pore (MPTP) opening. Aging leads to increased endoplasmic reticulum (ER) stress, which contributes to mitochondrial dysfunction, including reduced function of the ETC. The activation of both cytosolic and mitochondrial calcium-activated proteases termed calpains leads to mitochondrial dysfunction and decreased ETC function. Intriguingly, mitochondrial ROS generation also induces ER stress, highlighting the dynamic interaction between mitochondria and ER. Here, we discuss the role of ER stress in sensitizing and potentiating mitochondrial dysfunction in response to ischemia-reperfusion, and the promising potential therapeutic benefit of inhibition of ER stress and / or calpains to attenuate cardiac injury in elderly patients.

Endoplasmic reticulum (ER) stress contributes to cardiovascular disease including heart failure. Interactions between the ER and mitochondria during ER stress can impair the mitochondrial respiratory chain and increase cell injury. p53 is a tumor suppressor protein that regulates apoptosis. p53 contributes to the regulation of mitochondrial and ER interactions, especially during the progression of ER stress. The knockout (KO) of p53 leads to decreased injury in hearts following ischemia-reperfusion. We asked if KO of p53 can protect mitochondria during the induction of ER stress and decrease cell injury. Floxed p53 mice were crossed with mice carrying an α-myosin heavy chain cre to generate cardiac specific p53 KO mice. Thapsigargin (THAP) was used to induce ER stress in wild type (WT) and p53 KO mice. Mice were euthanized after 48 h THAP treatment. Cardiac mitochondria were isolated for functional measurement. TUNEL staining was used to assess myocyte death. In WT mice, THAP treatment decreased the rate of oxidative phosphorylation using pyruvate + malate as complex I substrates compared to vehicle-treated control. Complex I activity was also decreased in the THAP-treated WT mice. The rate of oxidative phosphorylation and complex I activity were not altered in THAP-treated p53 KO mice. The content of pyruvate dehydrogenase (PDH) α1 subunit was decreased in THAP-treated WT mice but not in p53 KO mice. ER stress led to a release of cytochrome c and apoptosis inducing factor from mitochondria into cytosol in WT but not in KO mice. Knockout of p53 also preserved mitochondrial bcl-2 content in THAP-treated mice. In WT mice, THAP treatment markedly increased cell death compared to vehicle treated hearts. In contrast, cell injury was decreased in THAP-treated p53 KO mice compared to corresponding wild type. Thus, KO of p53 decreased cell injury by protecting mitochondria during the ER stress.

Background ER (endoplasmic reticulum) stress leads to decreased complex I activity in cardiac mitochondria. The aim of the current study is to explore the potential mechanisms by which ER stress leads to the complex I defect. ER stress contributes to intracellular calcium overload and oxidative stress that are two key factors to induce mitochondrial dysfunction. Since oxidative stress is often accompanied by intracellular calcium overload during ER stress in vivo, the role of oxidative stress and calcium overload in mitochondrial dysfunction was studied using in vitro models. ER stress results in intracellular calcium overload that favors activation of calcium-dependent calpains. The contribution of mitochondrial calpain activation in ER stress-mediated complex I damage was studied. Methods Thapsigargin (THAP) was used to induce acute ER stress in H9c2 cells and C57BL/6 mice. Exogenous calcium (25 μM) and H2O2 (100 μM) were used to induce modest calcium overload and oxidative stress in isolated mitochondria. Calpain small subunit 1 (CAPNS1) is essential to maintain calpain 1 and calpain 2 (CPN1/2) activities. Deletion of CAPNS1 eliminates the activities of CPN1/2. Wild type and cardiac-specific CAPNS1 deletion mice were used to explore the role of CPN1/2 activation in calcium-induced mitochondrial damage. Results In isolated mitochondria, exogenous calcium but not H2O2 treatment led to decreased oxidative phosphorylation, supporting that calcium overload contributes a key role in the mitochondrial damage. THAP treatment of H9c2 cells decreased respiration selectively with complex I substrates. THAP treatment activated cytosolic and mitochondrial CPN1/2 in C57BL/6 mice and led to degradation of complex I subunits including NDUFS7. Calcium treatment decreased NDUFS7 content in wild type but not in CAPNS1 knockout mice. Conclusion ER stress-mediated activation of mitochondria-localized CPN1/2 contributes to complex I damage by cleaving component subunits.

Mobile phones come equipped with a vast array of actuation and sensing technologies, making them an ideal platform for point-of-care diagnostics and information gathering. Mobile phone microscopes take advantage of the small pixel size on mobile phone camera sensors for micron-scale resolution. Focusing can be achieved with built-in autofocus and image processing can be done on-board, however, the illumination is typically introduced via an external light emitting diode (LED). These external LEDs are typically externally powered, adding bulk and cost to a system that is meant to be as affordable as possible. In this work, we present a mobile phone microscope that uses the phone's integrated flash as an illumination source, eliminating the need to engineer an external illumination into the system. Our design consists of a 3D printed clip-on module containing a lens, which together with the mobile phone camera lens acts as an infinite-conjugate microscope. The clip-on module functions as a basic sample holder, and contains a series of light tunnels that redirect light from the flash through the sample for brightfield illumination. Instead of mirrors and a condenser lens, diffuse reflection from the internal light tunnel of the plastic clip-on module both reflects and scatters light into a range of illumination angles – ideal for brightfield microscopy. For low-contrast samples, darkfield imaging is achieved with ambient lighting via internal reflection within the sample microscope slide. We demonstrate imaging and video microscopy of a range of samples including plants, cell cultures and cattle semen.

Air embolism is a rare, often misdiagnosed, potentially fatal condition. It is most frequently associated with invasive vascular procedures and mechanical ventilation. Air emboli developing from peripheral intravenous lines are uncommon. We present a case of symptomatic venous air embolism likely arising from peripheral intravenous access gained during an interventional pain procedure. This case highlights the need to consider air embolism in the differential diagnoses of patients presenting with neurological symptoms following vascular interventions.

Oesophageal and gastric adenocarcinoma (OGA) treatment remains challenging. Improvements in early diagnosis, staging and management might have contributed to survival prolongation. To examine this hypothesis, we assessed outcomes of resected OGA patients in our institution over 10 years, comparing two time periods, 2001–2005 and 2006–2010. Records from patients who had undergone surgery with radical intent and follow-up for OGA were retrospectively reviewed. Patients followed up at hospitals other than the Royal Marsden Hospital were excluded. Two different cohorts were identified: patients with oesophageal and type I or type II oesophagogastric junction (OGJ) tumours, and patients with gastric and type III OGJ tumours. We identified 360 patients: 147 from 2001–2005 and 213 from 2006–2010. The characteristics were comparable across the two time periods. Between 2001–2005 and 2006–2010, the percentage of R0 resections increased (from 67.1 to 81.1 % for proximal tumours and from 76.3 to 95.9 % for gastric and type III OGJ tumours). The mean number of lymph nodes retrieved increased over time. The 5-year overall survival rate increased significantly from 42.3 to 56.6 % for proximal tumours and from 38.8 to 55.3 % for gastric and type III OGJ tumours. Similarly, the disease-free survival rate significantly increased from 34.6 to 53.5 % for proximal tumours and from 35.9 to 51.1 % for gastric and type III OGJ tumours. This study comprehensively describes the improvement in survival outcomes in a major UK referral centre over a 10-year period, identifying potentially relevant factors such as increased number of R0 resections and higher lymph node yield.

An intact immune system is critical for survival of hosts chronically infected with T. gondii. We observe clusters of immune cells surrounding regions of free parasite within brain tissue. Many of these cells are monocyte-derived and have parasite-limiting capacity, but the initial cues which instruct their proximity to parasite are not well understood. One potential mechanism of broad relevance is the incitement of damage. We explored the importance of IL-33, a protein released upon cell damage, in the recruitment of monocytes in our model. We found IL-33 to be expressed by oligodendrocytes during T. gondii infection, and observed regions of oligodendrocyte loss in infected mouse and human brain tissue, implying ample opportunity for IL-33 release. Upon infection, induction of the monocyte chemoattractant, CCL2, was dependent on IL-33 signaling, as visualized using CCL2-mcherry reporter mice. CCL2 signal was focal and expressed by astrocytes surrounding immune cell foci. The concept that IL-33 could be acting on astrocytes directly was supported by bone marrow chimeras which implicated a radio-resistant responder to IL-33. In alignment with CCL2 induction, IL-33 was required for infiltration of monocyte-derived myeloid cells, and expansion of focal myeloid cell-derived iNOS, an anti-parasitic mechanism crucial for survival during chronic infection. Consequently, intact IL-33 signaling was necessary for control of brain parasite burden. These results expand our knowledge of alarmin signaling in the brain, an environment which is likely unique to the periphery in immune response initiation due to the structural challenge of the BBB, and demonstrate the importance of one damage signal in focal control of T. gondii infection.

INTRODUCTION Non-occlusive small bowel necrosis (NOSBN) has been associated with early postoperative enteral feeding. The purpose of this study was to determine the incidence of this complication in an elective upper gastrointestinal (GI) surgical patient population and the influence of both patient selection and type of feeding jejunostomy (FJ) inserted, based on the experience of two surgical units in affiliated hospitals. PATIENTS AND METHODS The records were reviewed of 524 consecutive patients who underwent elective upper GI operations with insertion of a FJ for benign or malignant disease between 1997 and 2006. One unit routinely inserted needle catheter jejunostomies (NCJ), whilst the other selectively inserted tube jejunostomies (TJ). RESULTS Six cases of NOSBN were identified over 120 months in 524 patients (1.15%), with no difference in incidence between routine NCJ (n = 5; 1.16%) and selective TJ (n = 1; 1.06%). Median rate of feeding at time of diagnosis was 105 ml/h (range, 75–125 ml/h), and diagnosis was made at a median of 6 days (range, 4–18 days) postoperatively. All patients developed abdominal distension, hypotension and tachycardia in the 24 h before re-exploratory laparotomy. Five patients died and one patient survived. CONCLUSIONS The understanding of the pathophysiology of NOSBN is still rudimentary; nevertheless, its 1% incidence in the present study does call into question its routine postoperative use especially in those at high risk with an open abdomen, planned repeat laparotomies or marked bowel oedema. Patients should be fully resuscitated before initiating any enteral feeding, and feeding should be interrupted if there is any evidence of feed intolerance.