Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Designing microenvironments for optimal outcomes in tissue engineering and regenerative medicine: From biopolymers to culturing conditions

Bone marrow mesenchymal stem cells have been extensively used for tissue engineering and regenerative medicine applications due to their ease of isolation and expansion and their ability to differentiate towards various lineages of mesodermal origin. Despite these properties, their clinical potential is often hampered by the simplicity of the in vitro environment and its inability to resemble the complex in vivo niche. Herein, different microenvironmental cues (e.g. surface topography, substrate stiffness, mechanical stimulation, oxygen tension and co-culture systems) that have been utilised to enhance the therapeutic efficacy of bone marrow mesenchymal stem cells are discussed.The authors would like to acknowledge the following entities for financial support: H2020, Marie Skłodowska-Curie Actions, Innovative Training Networks 2015 Tendon Therapy Train project (Grant No. 676338); Science Foundation Ireland (SFI) / European Regional Development Fund (Grant Number 13/RC/2073); and SFI Career Development Award (Grant Number 15/CDA/3629)

Measurement of the cross-section for b-jets produced in association with a Z boson at root s=7 TeV with the ATLAS detector ATLAS Collaboration

A measurement is presented of the inclusive cross-section for b-jet production in association with a Z boson in pp collisions at a centre-of-mass energy of root s = 7 TeV. The analysis uses the data sample collected by the ATLAS experiment in 2010, corresponding to an integrated luminosity of approximately 36 pb(-1). The event selection requires a Z boson decaying into high P-T electrons or muons, and at least one b-jet, identified by its displaced vertex, with transverse momentum p(T) > 25 GeV and rapidity vertical bar y vertical bar < 2.1. After subtraction of background processes, the yield is extracted from the vertex mass distribution of the candidate b-jets. The ratio of this cross-section to the inclusive Z cross-section (the average number of b-jets per Z event) is also measured. Both results are found to be in good agreement with perturbative QCD predictions at next-to-leading order

'Numbness of the feet' is a poor indicator for polyneuropathy in Type 2 diabetic patients

Aims To identify neuropathic sensory symptoms associated with a clinical neurological examination (CNE) and to investigate whether these symptoms could be used as a diagnostic or screening tool for diabetic polyneuropathy in general practice. Methods Five hundred and eighty-eight patients with Type 2 diabetes, recruited from 26 general practices in the Netherlands, underwent a CNE and completed a diabetes symptom checklist that included 10 items on neuropathic sensory symptoms. Linear regression analyses were performed to assess the association between neuropathic symptoms and CNE. Receiver operating characteristic (ROC) curves were created to assess the diagnostic properties of neuropathic symptoms. Results In this population, with a mean age of 66.8 years, 32% were identified with diabetic polyneuropathy according to the CNE. Variables that showed the strongest association with CNE score were age (beta = 0.41), symptoms of sensory alteration (beta = 0.27), and the item 'numbness of the feet' (beta = 0.35) in particular. ROC curves showed that prediction of diabetic polyneuropathy from these symptoms was unsatisfying. The sensitivity and specificity of daily symptoms of 'numbness of the feet' were 28% and 93%, respectively, in patients <68 years, and 22% and 92%, respectively, in patients greater than or equal to 68 years. Conclusions Identification of neuropathic sensory symptoms is not useful as a diagnostic or even a screening tool in the assessment of diabetic neuropathy in daily practice. Therefore, the results reported in this paper mandate an annual foot examination by the general practitioner

'Numbness of the feet' is a poor indicator for polyneuropathy in Type 2 diabetic patients

Aims To identify neuropathic sensory symptoms associated with a clinical neurological examination (CNE) and to investigate whether these symptoms could be used as a diagnostic or screening tool for diabetic polyneuropathy in general practice. Methods Five hundred and eighty-eight patients with Type 2 diabetes, recruited from 26 general practices in the Netherlands, underwent a CNE and completed a diabetes symptom checklist that included 10 items on neuropathic sensory symptoms. Linear regression analyses were performed to assess the association between neuropathic symptoms and CNE. Receiver operating characteristic (ROC) curves were created to assess the diagnostic properties of neuropathic symptoms. Results In this population, with a mean age of 66.8 years, 32% were identified with diabetic polyneuropathy according to the CNE. Variables that showed the strongest association with CNE score were age (beta = 0.41), symptoms of sensory alteration (beta = 0.27), and the item 'numbness of the feet' (beta = 0.35) in particular. ROC curves showed that prediction of diabetic polyneuropathy from these symptoms was unsatisfying. The sensitivity and specificity of daily symptoms of 'numbness of the feet' were 28% and 93%, respectively, in patients <68 years, and 22% and 92%, respectively, in patients greater than or equal to 68 years. Conclusions Identification of neuropathic sensory symptoms is not useful as a diagnostic or even a screening tool in the assessment of diabetic neuropathy in daily practice. Therefore, the results reported in this paper mandate an annual foot examination by the general practitioner

Pregnancy interval and delivery outcome among HIV-seropositive and HIV-seronegative women in Kisumu, Kenya.

OBJECTIVE: A short pregnancy interval (PI) has been associated with increased child mortality, but mechanisms are unclear. We studied factors associated with PI and the effect of PI on birthweight and haemoglobin. METHODS: Information was analysed from 2218 multigravidae who were recruited at the prenatal clinic (1758) or in the labour ward (460) of the Provincial Hospital in Kisumu between June 1996 and July 2000 for a study to assess the interaction between placental malaria and vertical HIV transmission. RESULTS: The HIV prevalence was 28.9%. HIV seropositivity, older age, being unmarried, and <8 years of education were associated with a prolonged PI; among all women, a stillbirth, abortion, or death of a liveborn child as outcome of the previous pregnancy, and death of a child other than the last born among HIV-seronegative women, were associated with a shortened PI. No significant effect of short PI (an interval <24 months) on low birth weight (LBW), prematurity, small-for-gestational-age infants or maternal anaemia was evident. An abortion, stillbirth, or death of a liveborn child as outcome of the previous pregnancy was associated at the present delivery with LBW among HIV-seronegative women [adjusted odds ratio (AOR) 3.33, 95% confidence interval (CI) 1.63-6.81], and a low haemoglobin (<11 g/dl) among HIV-seropositive women (AOR 2.01, 95% CI 1.05-4.03 in the third trimester). CONCLUSION: Public health efforts to ensure 'adequate' birth spacing may run contrary to family planning decisions to replace a deceased child and may be spent on prenatal issues like prevention of anaemia, and vertical HIV transmission