Real-world learnings for digital health industryNHS collaboration: Life sciences vision in action.

Several publications have indicated potential benefit from collaboration with industry regarding wider use of anonymised routine NHS healthcare data. However, there is limited guidance regarding exactly how such collaborations between NHS hospitals and industry partners should best be carried out, and specific issues that need to be addressed at an individual project or collaboration level to achieve desired benefit. Specifically, routine health data are complex, not collected in a format optimised for secondary use, and often require interpretation based on clinical understanding of the medical conditions or patients.

Theory of Planned Behavior and Active Duty Air Force Members' Mental Health Help-Seeking.

Introduction: Although military members often encounter significant atypical stressors while serving, many service members are still reluctant to seek mental health (MH) treatment. Help-seeking behavior for MH needs is a rising concern for active duty Air Force personnel. Conditions such as post-traumatic stress disorder, depression, anxiety, and substance abuse are just a few issues that military members deal with, but things like stigma, attitudes toward MH, and behavioral control might keep these individuals from seeking services.

The extent of ionization in simulations of radio-loud AGNs impacting kpc gas discs.

We use the results of relativistic hydrodynamic simulations of jet-interstellar medium (ISM) interactions in a galaxy with a radio-loud AGN to quantify the extent of ionization in the central few kpcs of the gaseous galactic disc. We perform post-process radiative transfer of AGN radiation through the simulated gaseous jet-perturbed disc to estimate the extent of photo-ionization by the AGN with an incident luminosity of 10 erg s. We also map the gas that is collisionally ionized due to shocks driven by the jet.

Viscoelastic properties of human bladder tumours.

The urinary bladder is an organ which facilitates the storage and release of urine. The bladder can develop tumours and bladder cancer is a common malignancy throughout the world. There is a consensus that there are differences in the mechanical properties of normal and malignant tissues.

Differential expression of cytoprotective and apoptotic genes in an ischaemia-reperfusion isolated organ perfusion model of the transplanted kidney.

The optimal kidney preservation system and methods to ameliorate reperfusion injury are major factors in accomplishing successful graft function following transplantation. Ischaemia and reperfusion lead to cellular stress and the adaptive response may include the activation of genes involved in cellular protection and/or cell death by apoptosis. We investigated the expression of cytoprotective heme oxygenase-1 (HO-1), anti-apoptotic Bcl-2 and pro-apoptotic Bax after 6 h isolated organ perfusion in porcine kidneys that had been given 10 and 40 min warm ischaemic time.

The experimental agent pirfenidone reduces pro-fibrotic gene expression in a model of tacrolimus-induced nephrotoxicity.

Background: Tacrolimus nephrotoxicity is thought to contribute to renal allograft dysfunction and subsequent failure, a process that is underpinned by alterations in mRNA expression of genes involved in matrix metabolism. The new anti-fibrotic pirfenidone was tested for its potential to reverse markers of renal dysfunction.

Materials And Methods: Rats were salt-depleted before tacrolimus and pirfenidone treatment.

Cyclosporine and rapamycin act in a synergistic and dose-dependent manner in a model of immunosuppressant-induced kidney damage.

The combination of cyclosporine (CSA) and rapamycin (RAPA) is a potent and commonly used approach to immunosuppression following solid-organ transplantation. By applying varying doses of CSA and RAPA to the rat salt-depleted model, we aimed to find a dose combination that favored antiproliferation/antifibrosis rather than toxicity. Male Sprague-Dawley rats (350 to 500 g) were salt-depleted for 7 days prior to commencing CSA and RAPA treatment.

Mycophenolate mofetil inhibits intimal hyperplasia and attenuates the expression of genes favouring smooth muscle cell proliferation and migration.

Aim: Intimal hyperplasia remains the leading cause of late graft failure following heart transplantation. The immunosuppressive drug mycophenolate mofetil has been shown to inhibit the development of intimal hyperplasia. This study aimed to assess the efficacy of a combination of mycophenolate mofetil, calcineurin inhibition, and sirolimus on the development of intimal hyperplasia.

Prograf produces a molecular environment favoring antifibrosis, an effect reversed by the addition of rapamune.

Rapamune, an inhibitor of the mammalian target of rapamycin, exhibits antiproliferative actions and is increasingly used as adjuvant therapy with calcineurin inhibitors. This study investigated the effect of Rapamune on functional and molecular markers in a rat model of calcineurin inhibitor-induced graft dysfunction. Prograf (6 mg), with or without addition of Rapamune (1 mg), was administered to salt-depleted male rats (n = 6/group).

The novel antifibrotic agent pirfenidone attenuates the profibrotic environment generated by calcineurin inhibitors in the rat salt-depletion model.

Calcineurin inhibitors (CNIs) promote fibrosis in renal allografts by altering the dynamics of extracellular matrix (ECM) turnover. Graft structure is changed and functional disturbance may follow. This study examined the effects of an antifibrotic agent, pirfenidone, on functional, structural, and molecular markers of fibrosis in a rat model.

Differential effects of modern immunosuppressive agents on the development of intimal hyperplasia.

Modern immunosuppressive agents such as tacrolimus and rapamycin are claimed to be associated with a reduction in vascular narrowing, a central feature of chronic rejection. This study assesses the effect of cyclosporine, tacrolimus and rapamycin on the development of intimal thickening, fibrosis-associated genes and deposition of extracellular matrix (ECM) proteins in a model of intimal hyperplasia. Male Sprague-Dawley rats received either no treatment or 5 mg/kg cyclosporine, 0.

Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection.

Background: Acute allograft rejection is thought to be a risk factor for chronic allograft nephropathy, the cardinal features of which are vasculopathy, interstitial fibrosis and glomerulosclerosis. Fibrosis-associated genes might act as ad interim surrogate markers for chronic allograft nephropathy. The aim of this study was to determine mRNA expression of fibrosis-associated genes in glomeruli plucked from protocol renal transplant biopsies, in patients with or without a history of acute rejection.

The effect of combined rapamycin/cyclosporine on the changes in pro-fibrotic gene expression that occur during the development of allograft vasculopathy in rats, compared with cyclosporine or rapamycin in isolation.

Chronic allograft dysfunction, the leading cause of solid-organ transplant failure, is characterised by histological evidence of extracellular matrix (ECM) accumulation (fibrosis). The aim of this study was to compare the effect of combined rapamycin and cyclosporine therapy on fibrosis-associated gene expression and ECM turnover during the development of allograft vasculopathy, compared with either agent alone. Lewis recipients of F344 rat thoracic-to-abdominal aorta transplants were administered rapamycin, cyclosporine, combined rapamycin and cyclosporine or no treatment.

Rapamycin inhibits vascular remodeling in an experimental model of allograft vasculopathy and attenuates associated changes in fibrosis-associated gene expression.

Background: Rapamycin inhibits extracellular matrix (ECM) accumulation (fibrosis) and vascular remodeling in experimental models of chronic allograft dysfunction (CAD) by poorly understood mechanisms. The aim of this study was to assess the effect of rapamycin on the expression of fibrosis-associated genes and correlate this with observed changes in ECM remodeling in an experimental of model allograft vasculopathy.

Methods: Vascular remodeling and ECM accumulation (picrosirius red) were measured by computerized histomorphometry of F344-to-Lewis rat aortic allograft sections harvested at serial timepoints.

The impact of cyclosporine dose reduction with or without the addition of rapamycin on functional, molecular, and histological markers of chronic allograft nephropathy.

Background: Overexposure to cyclosporine is a risk factor for chronic allograft nephropathy (CAN) and dose reduction has been advocated. The purpose of this study was to determine the impact of adding the non-nephrotoxic immunosuppressant, rapamycin, after cyclosporine dose reduction in renal-allograft recipients with CAN.

Methods: Thirty-one patients with biopsy-confirmed CAN were prospectively randomized to receive a 40% cyclosporine dose reduction with (rapamycin, n=16) or without (control, n=15) the addition of rapamycin 2 mg/day.

Effects of the combination of rapamycin with tacrolimus or cyclosporin on experimental intimal hyperplasia.

Background: Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition.

Methods: Male Sprague-Dawley rats received rapamycin 0.

Microemulsion cyclosporin inhibits vascular remodelling and attenuates associated changes in profibrotic gene expression in an experimental model of allograft vasculopathy.

Background: Chronic allograft dysfunction (CAD), the leading cause of solid organ transplant failure, is characterized by histological evidence of extracellular matrix (ECM) accumulation (fibrosis). The aim of this study was to characterize the changes in fibrosis-associated gene expression in an experimental model of CAD and to measure the effect of the immunosuppressant cyclosporin on these changes.

Methods: Lewis recipients of F344 rat thoracic to abdominal transplants were administered cyclosporin or no treatment.

Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA.

Background: Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo-interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.

Methods: Forty renal allografts with stable renal function were biopsied 6 months after transplantation.

The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution.

Pirfenidone inhibits early myointimal proliferation but has no effect on late lesion size in rats.

Aims: intimal hyperplasia is mediated by smooth muscle cell proliferation, migration and deposition of extracellular matrix. The anti-fibrotic agent pirfenidone has been shown to inhibit pro-fibrotic growth factors in non-vascular inflammatory models. This study investigated the effect of the novel anti-fibrotic agent pirfenidone on the development of neointima.