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Offspring born from complicated pregnancies are at greater risk of cardiovascular disease in adulthood. Prenatal hypoxia is a common pregnancy complication that results in placental oxidative stress and impairs fetal development. Adult offspring exposed to hypoxia during fetal life are more susceptible to develop cardiac dysfunction, and show decreased cardiac tolerance to an ischemia/reperfusion (I/R) insult. To improve offspring cardiac outcomes, we have assessed the use of a placenta-targeted intervention during hypoxic pregnancies, by encapsulating the mitochondrial antioxidant MitoQ into nanoparticles (nMitoQ). We hypothesized that maternal nMitoQ treatment during hypoxic pregnancies improves cardiac tolerance to I/R insult in adult male and female offspring. Pregnant Sprague-Dawley rats were exposed to normoxia (21 % O 2 ) or hypoxia (11 % O 2 ) from gestational day 15-20, after injection with 100 μL saline or nMitoQ (125 μM) on GD15 (n=6-8/group). Male and female offspring were aged to 4 months. Both male and female offspring from hypoxic pregnancies showed reduced cardiac tolerance to I/R (assessed ex vivo using the isolated working heart technique) which was ameliorated by nMitoQ treatment. To identify potential molecular mechanisms for the changes in cardiac tolerance to I/R, cardiac levels/phosphorylation of proteins important for intracellular Ca 2+ cycling were assessed with Western blotting. In prenatally hypoxic male offspring, improved cardiac recovery from I/R by nMitoQ was accompanied by increased cardiac phospholamban and phosphatase 2Ce levels, and a trend to decreased Ca 2+ /calmodulin-dependent protein kinase IIδ phosphorylation. In contrast, in female offspring, nMitoQ treatment in hypoxic pregnancies increased phospholamban and protein kinase Cε phosphorylation. Maternal nMitoQ treatment improves cardiac tolerance to I/R insult in adult offspring and thus has the potential to improve the later-life trajectory of cardiovascular health of adult offspring born from pregnancies complicated by prenatal hypoxia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We present a case report of an 84-year-old male who presented with a profunda femoris artery (PFA) pseudoaneurysm 8 years after the index revision total hip arthroplasty procedure. Failure of revision hardware and subsequent migration of implants led to damage of the PFA and pseudoaneurysm formation. The patient was hemodynamically unstable on presentation and required emergent endovascular intervention. Once medically stabilized, the patient underwent extensive debridement of the aneurysm and hematoma bed and broken hardware was removed to prevent further complications. At 6-month follow-up, the patient was able to mobilize independently and had returned to all prior levels of activities of daily living. We discuss the vascular anatomy of the hip, the paucity of literature on PFA pseudoaneurysm, as well as the likely etiology of total hip arthroplasty failures., (© 2020 The Authors.)

Intrauterine growth restriction, a common consequence of prenatal hypoxia, is a leading cause of fetal morbidity and mortality with a significant impact on population health. Hypoxia may increase placental oxidative stress and lead to an abnormal release of placental-derived factors, which are emerging as potential contributors to developmental programming. Nanoparticle-linked drugs are emerging as a novel method to deliver therapeutics targeted to the placenta and avoid risking direct exposure to the fetus. We hypothesize that placental treatment with antioxidant MitoQ loaded onto nanoparticles (nMitoQ) will prevent the development of cardiovascular disease in offspring exposed to prenatal hypoxia. Pregnant rats were intravenously injected with saline or nMitoQ (125 μM) on gestational day (GD) 15 and exposed to either normoxia (21% O 2 ) or hypoxia (11% O 2 ) from GD15-21 (term: 22 days). In one set of animals, rats were euthanized on GD 21 to assess fetal body weight, placental weight and placental oxidative stress. In another set of animals, dams were allowed to give birth under normal atmospheric conditions (term: GD 22) and male and female offspring were assessed at 7 and 13 months of age for in vivo cardiac function (echocardiography) and vascular function (wire myography, mesenteric artery). Hypoxia increased oxidative stress in placentas of male and female fetuses, which was prevented by nMitoQ. 7-month-old male and female offspring exposed to prenatal hypoxia demonstrated cardiac diastolic dysfunction, of which nMitoQ improved only in 7-month-old female offspring. Vascular sensitivity to methacholine was reduced in 13-month-old female offspring exposed to prenatal hypoxia, while nMitoQ treatment improved vasorelaxation in both control and hypoxia exposed female offspring. Male 13-month-old offspring exposed to hypoxia showed an age-related decrease in vascular sensitivity to phenylephrine, which was prevented by nMitoQ. In summary, placental-targeted MitoQ treatment in utero has beneficial sex- and age-dependent effects on adult offspring cardiovascular function., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Understanding interactions between nanoparticles (NPs) with biological matter, particularly cells, is becoming increasingly important due to their growing application in medicine and materials, and consequent biological and environmental exposure. For NPs to be utilised to their full potential, it is important to correlate their functional characteristics with their physical properties, which may also be used to predict any adverse cellular responses. A key mechanism for NPs to impart toxicity is to gain cellular entry directly. Many parameters affect the behaviour of nanomaterials in a cellular environment particularly their interactions with cell membranes, including their size, shape and surface chemistry as well as factors such as the cell type, location and external environment (e.g. other surrounding materials, temperature, pH and pressure). Aside from in vitro and in vivo experiments, model cell membrane systems have been used in both computer simulations and physicochemical experiments to elucidate the mechanisms for NP cellular entry. Here we present a brief overview of the effects of NPs physical parameters on their cellular uptake, with focuses on 1) related research using model membrane systems and physicochemical methodologies; and 2) proposed physical mechanisms for NP cellular entrance, with implications to their nanotoxicity. We conclude with a suggestion that the energetic process of NP cellular entry can be evaluated by studying the effects of NPs on lipid mesophase transitions, as the molecular deformations and thus the elastic energy cost are analogous between such transitions and endocytosis. This presents an opportunity for contributions to understanding nanotoxicity from a physicochemical perspective., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Formal models of decision-making have traditionally focused on simple, two-choice perceptual decisions. To date, one of the most influential account of this process is Ratcliff's drift diffusion model (DDM). However, the extension of the model to more complex decisions is not straightforward. In particular, conflicting situations, such as the Eriksen, Stroop, or Simon tasks, require control mechanisms that shield the cognitive system against distracting information. We adopted a novel strategy to constrain response time (RT) models by concurrently investigating two well-known empirical laws in conflict tasks, both at experimental and modeling levels. The two laws, predicted by the DDM, describe the relationship between mean RT and (i) target intensity (Piéron's law), (ii) standard deviation of RT (Wagenmakers-Brown's law). Pioneering work has shown that Piéron's law holds in the Stroop task, and has highlighted an additive relationship between target intensity and compatibility. We found similar results in both Eriksen and Simon tasks. Compatibility also violated Wagenmakers-Brown's law in a very similar and particular fashion in the two tasks, suggesting a common model framework. To investigate the nature of this commonality, predictions of two recent extensions of the DDM that incorporate selective attention mechanisms were simulated and compared to the experimental results. Both models predict Piéron's law and the violation of Wagenmakers-Brown's law by compatibility. Fits of the models to the RT distributions and accuracy data allowed us to further reveal their relative strengths and deficiencies. Combining experimental and computational results, this study sets the groundwork for a unified model of decision-making in conflicting environments., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Both stabilization and orientation components of postural control are affected in Parkinson's disease (PD). These deficits are partly due to proprioceptive impairments, which frequently coexist with a visual dependence. This study aimed to evaluate if a visual biofeedback - i.e. real time anteroposterior trunk and head orientations indicated with a simplified avatar and represented in a head-mounted display - could improve the postural control of PD patients in response to a postural disturbance. The influence of focusing on one specific component of the postural control (stabilization or orientation) was also examined., Methods: Seventeen medicated PD patients performed sequences of pull-tests, either with eyes open, eyes closed or visual biofeedback, crossed with the verbal instruction to focus either on the stabilization or on the vertical body orientation. Kinematics data were collected., Results: Backward trunk tilts consequent to the pulls were unchanged across the different conditions. With eyes open and eyes closed, patients did not recover their initial vertical orientation by adopting a slightly tilted backward position. This bias disappeared with the visual biofeedback. Moreover, falls consecutive to the test were significantly less frequent with the visual biofeedback than in the two other visual conditions. These different orientation and stabilization parameters were not affected by the instruction., Conclusion: Unlike a verbal instruction, visualizing in real time their own body's geometry improved both components of postural control of PD patients. This provides evidences in PD about links between impaired vertical orientation, deficits in balance control, and contribution of supplementary sensory cues., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The principles of fast track surgery are well established in colorectal surgery. It is an evidence based model aimed at reducing length of stay, convalescence and morbidity by optimising both clinical and organisational factors. Despite this, the implementation of fast track surgery in breast cancer patients has been slow. The 23 h discharge model for breast cancer surgery patients has been outlined by the NHS Improvement Programme and is a breakthrough from traditional inpatient care. This paper outlines the early experience of implementation of this model in a single institution during a 3-month audit period. Over 80% of patients undergoing non-reconstructive breast surgery were discharged safely within '23 h'. This suggests that good communication links, reorganisation of existing resources, active user involvement (both patients and clinical team) and strong project management ensures fast-tracking to be safe for the patient with significant economic benefits for the hospital., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

Particles of surgical cobalt chrome alloy are cytotoxic and genotoxic to human fibroblasts in vitro. In vivo orthopaedic patients are exposed to cobalt chrome particles as a result of wear of a joint replacement. Many of the wear debris particles that are produced are phagocytosed by macrophages that accumulate at the site of the worn implant and are disseminated to local and distant lymph nodes the liver and the spleen. In this study we have tested whether this process of phagocytosis could have altered the cytotoxic and genotoxic properties of the cobalt chrome particles. Quartz particles have been investigated as a control. Micron-sized particles of cobalt chrome alloy were internalised by either white cells of peripheral blood or by THP-1 monocytes for 1 week and 1 day, respectively. The particles were then extracted and presented at different doses to fibroblasts for 1 day. There was a reduction of the cytotoxicity and genotoxicity of the cobalt chrome particles after phagocytosis by white cells or THP-1 cells. Cobalt chrome particles that were internalised by fibroblasts also showed a reduction of their cytotoxicity but not their genotoxicity. In contrast the cytotoxicity and genotoxicity of quartz particles was increased after internalisation by THP-1 cells. The surface morphology of the cobalt chrome particles but not the quartz particles was changed after phagocytosis by THP-1 cells. This study suggests that the genotoxic and cytotoxic properties of particles that fall within the size range for phagocytosis may be highly complex in vivo and depend on the combination of material type and previous phagocytosis. These results may have relevance for particle exposure from orthopaedic implants and from environmental or industrial pollution.

Untoward events involving radioactive material, either accidental or intentional, are potentially devastating. Hematologists and oncologists are uniquely suited to help manage radiation victims, as myelosuppression is a frequent complication of radiation exposure. In the aftermath of a large event, such as a nuclear detonation, there may be a national call for surge capacity that involves hematologists/oncologists across the country in the disaster response. In preparation, the National Marrow Donor Program and American Society for Blood and Marrow Transplantation have established the Radiation Injury Treatment Network (RITN), a voluntary consortium of transplant centers, donor centers, and umbilical cord blood banks. RITN is partnered with the Office of the Assistant Secretary for Preparedness and Response in the United States Department of Health and Human Services to develop treatment guidelines, educate healthcare professionals, coordinate situation response, and provide comprehensive evaluation and care for radiation injury victims. We outline the current plans for event response and describe scenarios, including catastrophic events that would require extensive support from hematologists/oncologists across the country. In addition, we highlight important reference resources and discuss current efforts to develop medical countermeasures against radiation toxicity. Practitioners and institutions across the country are encouraged to become involved and participate in the planning.

Background: To describe the utility of ultrasound biomicroscopy in diagnosing multiple bilateral iridociliary cysts and to determine the clinical significance of this condition., Methods: A retrospective review of 73 patients referred for ultrasound biomicroscopy who were found to have bilateral iridociliary cysts., Results: Seventy-three patients were identified who demonstrated 2 or more cysts in 1 eye and at least 1 in the other with ultrasound biomicroscopy. A solitary iris elevation was the most common reason for referral (84.9%). There were 44 patients for whom sufficient follow-up data were available, with a mean follow-up of 40.4 months. Clinical sequelae included 1 case of sectoral cataract (2.3%) and 4 cases of cyst-related glaucoma (9.1%)., Interpretation: Multiple bilateral iridociliary cysts is a common condition with occasional clinical significance. Ultrasound biomicroscopy is a valuable technique in diagnosing this condition. Patients who have significant angle compromise should be followed and treated as required for glaucoma.

Background: Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease (CAD). Apart from traditional risk factors complement activation and inflammation may trigger and sustain endothelial dysfunction. We sought to assess the association between endothelial function, high sensitivity C-reactive protein (hs-CRP) and markers of complement activation in patients with either stable or unstable coronary artery disease., Methods: We prospectively recruited 78 patients, 35 patients with stable angina pectoris (SAP) and 43 patients with unstable angina pectoris (UAP). Endothelial function was assessed as brachial artery reactivity (BAR). Hs-CRP, C3a, C5a and C1-Inhibitor (C1 inh.) were measured enzymatically., Results: Patients with UAP showed higher median levels of hs-CRP and C3a compared to patients with SAP, while BAR was not significantly different between patient groups. In UAP patients, hs-CRP was significantly correlated with cholesterol (r=0.27, p<0.02), C3a (r=0.32, p<0.001) and C1 INH.(r=0.41, p<0.003), but not with flow mediated dilatation (r=0.09, P=0.41). Hs-CRP and C1 INH.were found to be independent predictors of UAP in a backward stepwise logistic regression model., Conclusions: We conclude that both hs-CRP, a marker of inflammation and C3a, a marker of complement activation are elevated in patients with UAP, but not in patients with SAP.

Although, several studies have been reported on the effects of oxidants on the structure and function of other molecular chaperones, no reports have been made so far for the chaperonin GroEL. The ability of GroEL to function under oxidative stress was investigated in this report by monitoring the effects of hydrogen peroxide (H(2)O(2)) on the structure and refolding activity of this protein. Using fluorescence spectroscopy and light scattering, we observed that GroEL showed increases in exposed hydrophobic sites and changes in tertiary and quaternary structure. Differential sedimentation, gel electrophoresis, and circular dichroism showed that H(2)O(2) treated GroEL underwent irreversible dissociation into monomers with partial loss of secondary structure. Relative to other proteins, GroEL was found to be highly resistant to oxidative damage. Interestingly, GroEL monomers produced under these conditions can facilitate the reactivation of H(2)O(2)-inactivated rhodanese but not urea-denatured rhodanese. Recovery of approximately 84% active rhodanese was obtained with either native or oxidized GroEL in the absence of GroES or ATP. In comparison, urea-denatured GroEL, BSA and the refolding mixture in the absence of proteins resulted in the recovery of 72, 50, and 49% rhodanese activity, respectively. Previous studies have shown that GroEL monomers can reactivate rhodanese. Here, we show that oxidized monomeric GroEL can reactivate oxidized rhodanese suggesting that GroEL retains the ability to protect proteins during oxidative stress.

A 12-month-old Golden Retriever bitch underwent unilateral hip arthroplasty following a diagnosis of coxofemoral osteoarthritis secondary to hip dysplasia. The hip prosthesis underwent aseptic loosening and was removed 6 months after implantation. Synovial biopsies taken at that time revealed scattered foci of granulomatous inflammation associated with intra-cytoplasmic and extracellular particulate material. Electron microscopical analyses demonstrated that this material contained cobalt, chromium, titanium and zirconium, which was probably wear debris from the loosened prosthesis. In human patients with hip arthroplasty, widespread dissemination of wear debris from loosened prostheses occasionally occurs, with an increased prevalence of neoplasia. A similar phenomenon may be predicted to occur with the increasing use of hip arthroplasty in the dog.

Raw (unpasteurized) milk can be a source of food-borne pathogens. Raw milk consumption results in sporadic disease outbreaks. Pasteurization is designed to destroy all bacterial pathogens common to raw milk, excluding spore-forming bacteria and possibly Mycobacterium paratuberculosis , but some people continue to drink raw milk, believing it to be safe. Current methods for assessing the bacteriological quality of raw milk, such as aerobic plate counts, are not usually designed to detect specific pathogens. The objective of this study was to estimate the proportion of pick-ups (loads of raw milk from a single farm bulk tank) from Ontario farm bulk tanks that contained Listeria monocytogenes . Salmonella spp., Campylobacter spp., and/or verotoxigenic Escherichia coli (VTEC). Samples from 1,720 pick-ups of raw milk were tested for the presence of these pathogens, and 47 L. monocytogenes , three Salmonella spp., eight Campylobacter spp., and 15 VTEC isolates were detected, representing 2.73, 0.17, 0.47, and 0.87% of milk samples, respectively. Estimates of the proportion of theoretical tanker truck loads of pooled raw milk contaminated with pathogens ranged from a low of 0.51 % of tankers containing raw milk from 3 bulk tanks being contaminated with Salmonella spp. to a high of 34.41 % of tankers containing raw milk from 10 bulk tanks being contaminated with at least one of the pathogens. Associations between the presence of pathogens and raw milk sample characteristics were investigated. The mean somatic cell count was higher among VTEC- or L. monocytogenes -positive samples, and the mean aerobic plate count was found to be higher among L. monocytogenes -positive samples. These results confirm the presence of bacterial food pathogens in raw milk and emphasize the importance of continued diligence in the application of hygiene programs within dairies and the separation of raw milk from pasteurized milk and milk products.

We reviewed 22,486 consecutive autopsy reports in a single District General Hospital, from 1953 to 1992. Five hundred and eighty-one patients with fractures of the proximal femur (hip fracture) were identified. Causes of death were correlated with timing of surgery and change of clinical practice. Thromboembolic and haemorrhagic potential were analysed. The principal causes of death after hip fracture were bronchopneumonia, cardiac failure, myocardial infarction and pulmonary embolism. Surgical intervention, within 24 h of injury significantly reduced death from bronchopneumonia and pulmonary embolism. Early mobilization reduced death from bronchopneumonia. Pulmonary embolism may be reduced by prophylactic anticoagulation, but 17 per cent of patients are at risk of haemorrhage, and mechanical methods seem safer in this population.

Cardiac pacing in children has undergone many improvements in the last decade. The differences between adult and pediatric pacing have narrowed. Children are no longer being denied pacemakers because of size. This article discusses techniques for pacing pediatric patients successfully that will allow them to lead normal lives.

We report a case of myocardial necrosis in a newborn after treatment of the mother with long-term subcutaneous terbutaline. No such serious side effects in the fetus have previously been reported. We speculate that this myocardial damage was due to beta-sympathomimetic therapy.

Resuscitation for cardiac arrest was monitored over 4 years to examine the effect on survival of a change in the ventricular fibrillation (VF) protocol to include the routine early use of "high-dose" intravenous or transbronchial adrenaline. A significant reduction in the immediate survival of patients with VF was seen when the protocol was changed (22% after the change, 43% before). Prior predictors of poor response were similar in each group, except for the number of witnessed arrests, delay until cardiopulmonary resuscitation, and occurrence of endotracheal intubation, but multiple logistic regression showed the use of adrenaline to be an independent predictor of outcome. Early high-dose adrenaline was associated with a reduction in immediate survival in patients with persistent VF.