Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment

Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment

It Is the time to think about a treat-to-target strategy for knee osteoarthritis

Osteoarthritis (OA) is a rheumatic disease that affects the well-being of the patient, compromises physical and mental function, and affects other quality of life aspects. In the literature, several evidence-based guidelines and recommendations for the management of knee osteoarthritis (KOA) are available. These recommendations list the different therapeutic options rather than addressing a hierarchy between the treatments and defining the real target. Therefore, a question arises: are patients and physicians satisfied with the current management of KOA? Actually, the answer may be negative, thus suggesting a change in our therapeutic strategies. In this article, we address this challenge by suggesting that it is time to develop a “treat to target strategy” for KO

Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice

Recognition of other's emotions influences the way social animals interact and adapt to the environment. The neuropeptide oxytocin (OXT) has been implicated in different aspects of emotion processing. However, the role of endogenous OXT brain pathways in the social response to different emotional states in conspecifics remains elusive. Here, using a combination of anatomical, genetic, and chemogenetic approaches, we investigated the contribution of endogenous OXT signaling in the ability of mice to discriminate unfamiliar conspecifics based on their emotional states. We found that OXTergic projections from the paraventricular nucleus of the hypothalamus (PVN) to the central amygdala (CeA) are crucial for the discrimination of both positively and negatively valenced emotional states. In contrast, blocking PVN OXT release into the nucleus accumbens, prefrontal cortex, and hippocampal CA2 did not alter this emotion discrimination. Furthermore, silencing each of these PVN OXT pathways did not influence basic social interaction. These findings were further supported by the demonstration that virally mediated enhancement of OXT signaling within the CeA was sufficient to rescue emotion discrimination deficits in a genetic mouse model of cognitive liability. Our results indicate that CeA OXT signaling plays a key role in emotion discrimination both in physiological and pathological conditions. Is endogenous oxytocin implicated in emotion discrimination? Ferretti, Maltese et al. demonstrate that oxytocin signaling in the central amygdala plays a key role in the ability of mice to discriminate unfamiliar conspecifics based on their emotional state, both in physiological and genetically determined pathological conditions

Results of the Sophia module intercomparison part-1: stc, low irradiance conditions and temperature coefficients measurements of C-Si technologies

The results of a measurement intercomparison between eleven European laboratories measuring PV energy relevant parameters are reported. The purpose of the round-robin was to assess the uncertainty analyses of the participating laboratories on c-Si modules and to establish a baseline for the following thin-film round-robin. Alongside the STC measurements, low irradiance conditions (200W/m2) and temperature coefficients measurements were performed. The largest measurement deviation from the median at STC was for HIT modules from -3.6% to +2.7% in PMAX, but in agreement with the stated uncertainties of the participants. This was not the case for low irradiance conditions and temperature coefficients measurements with some partners underestimating their uncertainties. Larger deviations from the median from -5% to +3% in PMAX at low irradiance conditions and -6.6% to +18.3% for the PMAX temperature coefficient were observed. The main sources of uncertainties contributing to the spread in measurements were the RC calibration, mismatch factor and capacitive effects at STC and low irradiance conditions as well as the additional light inhomogeneity for the latter. The uncertainty in the junction temperature and the temperature deviation across the module were the major contributors for temperature coefficients measurements

Uncertainty in energy yield estimation based on C-Si module roundrobin results.

Results of the European FP7 Sophia project roundrobin of c-Si module power measurements at STC and low irradiance and temperature coefficients were used to calculate annual energy yield at four sites. The deviation in the estimates solely due to the different measurement results is reported, neglecting the uncertainty in the meteorological data and losses unrelated to the performed measurements. While minimising the deviation in Pmax measurements remains the key challenge, the low irradiance and temperature coefficient contributions are shown to be significant. Propagating the measurement deviation in c-Si module measurements would suggest that expanded uncertainty in energy yield due to module characterization alone can be as high as ±3-4%

Signaling pathways responsible for the rapid antidepressant-like effects of a GluN2A-preferring NMDA receptor antagonist

In a previous study we found that the preferring GluN2A receptor antagonist, NVP-AAM077, elicited rapid antidepressant-like effects in the forced swim test that was related to the release of glutamate and serotonin in the medial prefrontal cortex. In the present work we sought to examine the duration of this behavioral effect as well as the molecular readouts involved. Our results showed that NVP-AAM077 reduced the immobility in the forced swim test 30?min and 24?h after its administration. However, this effect waned 7 days later. The rapid antidepressant-like response seems to be associated with increases in the GluA1 subunit of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, mammalian target of rapamycin (mTOR) signaling, glia markers such as glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter 1 (EAAT1), and a rapid mobilization of intracellular stores of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex.Acknowledgements: M.G.-S. was recipient of a contract from the Sistema Nacional de Garantía Juvenil co-funded by the European Social Fund. We also thank Novartis for the generous gift of NVP-AAM077. This work was supported by the Instituto de Salud Carlos III, Subdirección General del Evaluación y Fomento de la Investigación (FIS Grants PI13/00038 and PI16/00217) that were co-funded by the European Regional Development Fund (‘A way to build Europe’). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged

Efficacy of a single intra-articular HYMOVIS ONE injection for managing symptomatic hip osteoarthritis: A 12-month follow-up retrospective analysis of the ANTIAGE register data

The use of ultrasound (US) guidance has allowed hip osteoarthritis to be treated with intra-articular (IA) injections. HYMOVIS ONE (HYADD4-G) is a new hyaluronic acid (HA) derivative product with unusual characteristics, and it has been used with good results in knee osteoarthritis (OA). This study assessed the efficacy and safety of a single HYMOVIS ONE injection in patients affected by symptomatic hip OA

Efficacy of a single intra-articular HYMOVIS ONE injection for managing symptomatic hip osteoarthritis: A 12-month follow-up retrospective analysis of the ANTIAGE register data

Purpose: The use of ultrasound (US) guidance has allowed hip osteoarthritis to be treated with intra-articular (IA) injections. HYMOVIS ONE (HYADD4-G) is a new hyaluronic acid (HA) derivative product with unusual characteristics, and it has been used with good results in knee osteoarthritis (OA). This study assessed the efficacy and safety of a single HYMOVIS ONE injection in patients affected by symptomatic hip OA. Patients and Methods: This post-marketing cohort study assessed data from the ANTIAGE Register. Inclusion criteria were age ≥40 years, symptomatic hip OA (Kellgren-Lawrence grade I–III) of ≥1-year duration, and ≥12 months follow-up. All patients received a single HYMOVIS ONE (32 mg/4 mL) injection at baseline. Values for 10-cm visual analogue scale (VAS) pain scores, the Lequesne index, and nonsteroidal anti–inflammatory drug (NSAID) consumption were evaluated at 6 and 12 months. Adverse events were also recorded. Results: The included patients (n = 198) consisted of 42.5% women, with a mean (± SD) age at baseline of 62 (± 14.2) years and a mean (± SD) body mass index of 26.3 (± 2.5). The mean (SD) Lequesne index and VAS pain scores at baseline were 11.5 (± 4.6) and 6.4 cm (± 2.2), respectively. All groups exhibited statistically significant reductions at all time points compared to baseline. At 12 months, the VAS pain score was reduced by 17.2%, the Lequesne index by 33.7%, and NSAID consumption by 41.7%. Conclusion: Our study supports the clinical efficacy and safety of a single HYMOVIS ONE injection for managing symptoms in patients with hip OA, confirming previous data on the use of HYMOVIS as a background therapy in the management of knee osteoarthritis