Identification of new HIV-1 Gag-specific cytotoxic T lymphocyte responses in BALB/c mice

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The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate

Simple Summary A number of skeletal disorders, all characterized by a metabolic or neoplastic loss of bone tissue, are cured with drugs called Bisphosphonates (BPs), which exert their therapeutic effect by suppressing cells named osteoclasts, normally mediating bone resorption. Unfortunately, these drugs can also provoke a dangerous side effect known as osteonecrosis of the jaw (ONJ), a bone infection localized in the oral cavity and characterized by gingival ulceration, sometimes accompanied by suppuration and pain. This condition, occasionally arising spontaneously, is more often started by a tooth extraction. The reduced number of osteoclasts, determined by BPs, is thought to favor the bacterial invasion of healthy bone and the incapacity to eliminate infected bone, that are in turn responsible for the appearance of ONJ. Here we show that Magnesium, used for decades as dietary supplement, can invert the effect of BPs, transforming them, through a sort of paradox effect, into powerful activators of osteoclast production. These results suggest that Magnesium might be used in a topical approach aimed to cure or prevent ONJ. Notably, the capacity of Magnesium to activate osteoclast production was even observed in absence of BPs, suggesting its application also in ONJ forms caused by agents distinct to BPs.Abstract Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ

Quality of life and anxious-depressive symptoms in cancer patients undergoing mindfulness-based interventions: Feasibility and preliminary outcomes on prospective single-centre case-control study (MIND4ME St.)

Background Mindfulness based interventions (MBIs) have shown efficacy in improving psychological symptoms including depression and anxiety in cancer patients (pts). The study aimed to explore feasibility and reproducibility of MBIs in an Italian Cancer Centre measuring biochemical and psychological parameters. Methods In this pilot prospective case-control study, we recruited newly diagnosed pts receiving adjuvant chemotherapy (CT). A MBIs program was designed consisting of 2.5 hours weekly for 8 weeks and, including meditation, yoga and body scan. Material for 45 minutes (mn) home daily practice was provided. Primary endpoint was to evaluate feasibility. Secondary endpoints were assessment of quality of life (QoL), psychological and biochemical outcomes of stress, tested at baseline (W0), W4, W8, W24, W48. PSS (Perceived Stress Reduction), POMS (profile of mood states scores), EuroQoL (EQ-5D-3L) were administered. Results Ten pts underwent MBIs program arm. We present preliminary results, while data of control arm are being collected. All pts were female, two pts (20%) dropped out. Median age was 56 years. All received adjuvant CT, 5/8 received radiotherapy and hormone therapy. Mean of sessions attending was 6.8 (76%). Median daily practice was 30 mn. EQ-5D item for depression and anxiety showed decreasing trend in mean score from moderate to light (P = 0.15) and significant improvement of auto-perceived QoL was observed comparing W0 and W8 (P = 0.02) Conclusions In a sensitive setting such as start CT, we found high pts compliance to MBIs. Improvement in self-perceived QoL after starting program was found and comparing anxious-depressive symptoms outcomes with control arm is still needed

Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. alpha(2A)/alpha(2C)-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data