Publications by authors named "Stephen Rothwell"

Sleep disturbances are common among disorders associated with hypothalamic pituitary-adrenal (HPA) axis dysfunction, such as depression and anxiety. This comorbidity may partly be the result of the intersection between the role of the HPA axis in mediating the stress response and its involvement in sleep-wake cyclicity. Our previous work has shown that following 20 h of sleep restriction, mice show a blunting of the HPA axis in response to an acute stressor.

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Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection.

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One in three adults reports experiencing inadequate or disrupted sleep throughout the night, with the incidence being higher in women than in men. Disturbances in nightly sleep result in physiological alterations that contribute to a number of disorders. Poor sleep quality is believed to contribute to the pathogenesis of these disorders through interactions with the hypothalamic-pituitary-adrenal (HPA) axis.

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Article Synopsis
  • Poor sleep hygiene negatively impacts various biological systems, especially through dysfunction in the pituitary gland, which regulates sleep and stress responses.
  • A study analyzed gene expression changes in mice after 12 hours of sleep deprivation, followed by a stress test, revealing significant differences in gene expression related to hormone secretion and the stress response.
  • The findings highlighted sex-specific differences in gene responses, with a notable increase in differentially expressed genes after sleep deprivation followed by stress, suggesting potential genetic targets for understanding sleep and stress interactions.
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Rats are a common model for the study of bone healing, with the cranium, femur, and tibia being the bones studied most frequently. This study examines noncritical-sized lesions that would allow rats to continue to bear weight without the need for fixation but that are sufficiently large to enable characterization of the healing process. We compared the femoral bone strength associated with 3 lesion sizes selected for use in future studies.

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Management of pain in research swine used for studies involving painful procedures is a considerable challenge. Here we assessed whether a regional anesthesia method is effective for pain control of hindlimb injuries in pigs used for research in bone fracture healing. For this randomized controlled study, we administered regional anesthesia before an experimental femoral injury was produced.

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Here we report results of non-invasive measurements of indirect markers of soft tissue healing of traumatic wounds in an observational swine study and describe the quantification of analog physiological signals. The primary purpose of the study was to measure bone healing of fractures with four different wound treatments. A second purpose was to quantify soft tissue wound healing by measuring the following indirect markers: (1) tissue oxygenation, (2) fluid content, and (3) blood flow, which were all measured by non-invasive modalities, measured with available devices.

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Introduction: Military servicemembers in combat operations often sustain injuries to the extremities from highspeed projectiles, resulting in bleeding and comminuted open fractures. Severe injury with bone fragmentation can result in limb amputation. Surgical treatment options include materials that promote osteogenesis and bone proliferation, such as growth hormones, stem cells, or mineralized matrix adjuncts.

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We have previously shown that lyophilized salmon thrombin and fibrinogen (STF) embedded in a dissolvable dextran dressing is as efficacious as Combat Gauze (CG) with regard to controlling hemorrhage and survival in non-coagulopathic swine with femoral artery lacerations. A major limitation of currently available advanced field dressings is the inability to control hemorrhage in coagulopathic casualties because of the exhaustion of host coagulation proteins. We tested the hypothesis that the STF dressing would be better able to control hemorrhage and prolong survival in coagulopathic swine compared to CG.

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Background: Battlefield hemorrhage remains the primary cause of death in potentially survivable combat injuries with noncompressible hemorrhage. Fibrin dressings have great potential for reducing mortality, however are limited by cost, availability, and disease transmission.

Methods: Dressings comprising a soluble dextran dressing with lyophilized salmon thrombin and fibrinogen (STF) were tested against Combat Gauze (CG) as a control in a standard swine femoral artery hemorrhage model.

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Obesity is known to be associated with a large number of long-term morbidities, and while in some cases the relationship of obesity and the consequences is clear (for example, excess weight and lower extremity orthopedic problems) in others the mechanism is not as clear. One common system of categorizing overweight in terms of the likelihood of negative consequences involves using the concept of "metabolic syndrome". We hypothesized that the development of a plasma protein profile of overweight adolescents with and without the metabolic syndrome might give a more precise and informative picture of the disease process than the current clinical categorization and permit early targeted intervention.

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The incidence of cardiovascular diseases is ten-times higher in males than females, although the biological basis for this gender disparity is not known. However, based on the fact that antiplatelet drugs are the mainstay for prevention and therapy, we hypothesized that the signaling proteomes in platelets from normal male donors might be more activated than platelets from normal female donors. We report here that platelets from male donors express significantly higher levels of signaling cascade proteins than platelets from female donors.

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Experimental salmon thrombin/fibrinogen dressings have been shown to provide effective hemostasis in severe hemorrhage situations. The hypothesis for this study was that swine would still remain healthy without coagulopathy six months after exposure to salmon thrombin/fibrinogen dressings. Initial exposure was by insertion of the salmon dressing into the peritoneal cavity.

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We investigated the inflammatory response in pigs exposed to salmon fibrinogen/thrombin dressings. Animals were exposed to the material in 3 ways: (a) thrombin and fibrinogen were injected intravenously, (b) dual full-thickness skin lesions were surgically created on the dorsal aspect of the swine and treated with the fibrinogen/thrombin bandage and a commercial bandage or (c) a fibrinogen/thrombin bandage was inserted through an abdominal incision into the peritoneal cavity. Blood was collected twice weekly and animals were sacrificed at 7, 10 or 28 days.

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Proteomics for clinical applications is presently in a state of transition. It has become clear that the classical approaches based on 2-DE and/or MS need to be complemented by different kinds of technologies. The well-known problems include sample complexity, sensitivity, quantitation, reproducibility, and analysis time.

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The intracellular fates of soluble and liposomal antigens in human macrophages and dendritic cells are not well defined. Previous studies using murine macrophages have demonstrated that liposomal antigens can enter the MHC class I pathway. The Golgi complex is a major organelle in this pathway.

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Background: Recently, a wide variety of bandages have been formulated to attempt to improve the effectiveness of emergency intervention in situations of uncontrolled bleeding. The best of these dressings contain a mixture of human thrombin and fibrinogen. The presence of human components in these bandages, although effective, increases the cost of the dressing and raises questions of availability of raw materials and transmission of pathogens.

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Antigen-presenting cells readily phagocytose antigens and channel them through various membrane-bound organelles within the cell. In previous studies, we demonstrated that macrophages concentrated and localized particulate antigens to the trans-Golgi prior to displaying the MHC-class I-antigenic peptides on the cell surface. In this study, we evaluated the importance of cytoskeletal elements in the intracellular trafficking of soluble and liposome-encapsulated ovalbumin in murine bone marrow-derived macrophages and human dendritic cells.

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Cholesterol is a major constituent of plasma cell membranes and influences the functions of proteins residing in the membrane. To assess the role of cholesterol in phagocytosis and intracellular trafficking of liposomal antigen, macrophages were treated with inhibitors of cholesterol biosynthesis for various time periods and levels of cholesterol depletion were assessed by thin layer chromatography. In control macrophages, cholesterol was present in the plasma membrane and in intracellular stores, as visualised by staining with the cholesterol-binding compound filipin, whereas macrophages treated with cholesterol inhibitors failed to stain with filipin.

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epsilon -Amino caproic acid (EACA), a lysine analog that inhibits the activity of plasmin, was added to Nycomed (TC-S) fibrin bandages, and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. The blood loss using the bandage with EACA (TC-S+EACA; 728.8+/-132 g, n=5) was much greater as compared to the TC-S bandage alone (TC-S; 237.

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