Cardiovascular morbidity and mortality in patients with rheumatic disease: hyperuricemia,a forgotten puzzle piece?

Clinical Rheumatology -     

Immunotherapeutic Synergy Between Anti-CD137 mAb and Intratumoral Administration of a Cytopathic Semliki Forest Virus Encoding IL-12

Intratumoral injection of Semliki Forest virus encoding interleukin-12 (SFV-IL-12) combines acute expression of IL-12 and stressful apoptosis of infected malignant cells. Agonist antibodies directed to costimulatory receptor CD137 (4-1BB) strongly amplify pre-existing cellular immune responses toward weak tumor antigens. In this study, we provide evidence for powerful synergistic effects of a combined strategy consisting of intratumoral injection of SFV-IL-12 and systemic delivery of agonist anti-CD137 monoclonal antibodies (mAbs), which was substantiated against poorly immunogenic B16 melanomas (B16-OVA and B16.F10) and TC-1 lung carcinomas. Effector CD8_β⁺ T cells were sufficient to mediate complete tumor eradications. Accordingly, there was an intensely synergistic in vivo enhancement of cytotoxic T lymphocytes (CTL)-mediated immunity against the tumor antigens OVA and tyrosine-related protein-2 (TRP-2). This train of phenomena led to long-lasting tumor-specific immunity against rechallenge, attained transient control of the progression of concomitant tumor lesions that were not directly treated with SFV-IL-12 and caused autoimmune vitiligo. Importantly, we found that SFV-IL-12 intratumoral injection induces bright expression of CD137 on most tumor-infiltrating CD8⁺ T lymphocytes, thereby providing more abundant targets for the action of the agonist antibody. This efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-CD137 mAbs are already undergoing clinical trials and development of clinical-grade SFV-IL-12 vectors is in progress.     

Evaluation of a Neural Network-Based Control Strategy for a Cost-Effective Externally-Powered Prosthesis

ABSTRACT

This paper presents a control strategy that compensates for the nonlinearity in the inexpensive sensors and hardware of a cost effective prosthetic hand. The control strategy uses neural network-based force control and sensory feedback to detect disturbance induced by slippage. The neural network approach is chosen over other nonlinear models because it is easy to implement and it offered the additional advantage of having its parameters easily adjusted over the life span of the device. The proposed strategy was evaluated on a functional multi-digit underactuated prosthetic hand. The initial and incremental forces exerted from each finger were adjusted to balance the amount of disturbance and the deformation of the objects. Experiments were conducted to test the performance of the protocol in situations encountered in activities of daily living. The displacement of each object under three grasping configurations was measured as a performance criterion while the object's mass was changed. The results showed that with the adjusted parameters for each grasping configuration, the control strategy was able to detect the dynamic changes in mass of the object and was also able to successfully adjust the grasping force before the object drops from the hand.     

Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration

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Current knowledge on tumour induction by computed tomography should be carefully used

Risks associated to ionising radiation from medical imaging techniques have focused the attention of the medical society and general population. This risk is aimed to determine the probability that a tumour is induced as a result of a computed tomography (CT) examination since it makes nowadays the biggest contribution to the collective dose. Several models of cancer induction have been reported in the literature, with diametrically different implications. This article reviews those models, focusing on the ones used by the scientific community to estimate CT detriments. Current estimates of the probability that a CT examination induces cancer are reported, highlighting its low magnitude (near the background level) and large sources of uncertainty. From this objective review, it is concluded that epidemiological data with more accurate dosimetric estimates are needed. Prediction of the number of tumours that will be induced in population exposed to ionising radiation should be avoided or, if given, it should be accompanied by a realistic evaluation of its uncertainty and of the advantages of CTs. Otherwise they may have a negative impact in both the medical community and the patients. Reducing doses even more is not justified if that compromises clinical image quality in a necessary investigation. Key Points ? Predictions of radiation-induced cancer should be discussed alongside benefits of imaging. ? Estimates of induced cancers have noticeable uncertainties that should always be highlighted. ? There is controversy about the acceptance of the linear no-threshold model. ? Estimated extra risks of cancer are close to the background level. ? Patients should not be alarmed by potential cancer induction by CT examinations.     

Exploring motor and visual imagery in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by the progressive atrophy of both the first and the second motor neurons. Although the cognitive profile of ALS patients has already been defined by the occurrence of language dysfunctions and frontal deficit symptoms, it is less clear whether the degeneration of upper and lower motor neurons affects motor imagery abilities. Here, we directly investigated motor imagery in ALS patients by means of an established task that allows to examine the presence of the effects of the biomechanical constraints. Twenty-three ALS patients and 23 neurologically unimpaired participants have been administered with the (1) hand laterality task (HLT) in which participants were asked to judge the laterality of a rotated hand and the (2) mirror letter discrimination task (MLD) in which participants were asked to judge whether a rotated alphanumeric character was in its canonical or mirror-reversed form (i.e. control task). Results show that patients present the same pattern of performance as unimpaired participants at the MLD, while at the HLT, they present only partially with the effects of biomechanical constraints. Taken together, our findings provide evidences that motor imagery abilities, related to the mental simulation of an action, are affected by this progressive disease.