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Background: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response., Methods: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors., Results: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors., Conclusion: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A non-isothermal transformation model was proposed to determine the austenite formation kinetics in a steel alloyed with 2.6% wt. Si by dilatometric analysis, considering that the nucleation mechanism does not change with the heating rate. From the dilatometric analysis, it was observed that the austenite formation occurs in two stages; critical temperatures, degree and austenite formation rate were determined. The activation energies associated with each of the stages were obtained employing the Kissinger method (226.67 and 198.37 kJ·mol -1 for the first and second stage) which was used in concert with the austenite formation rate in the non-isothermal model as a first approximation, with acceptable results in the second stage, but not in the first due to the activation energies magnitude. Then, the activation energies were adjusted by minimizing the minimal squares error between estimated and experimental austenite formation degree, obtaining values of 158.50 kJ·mol -1 for the first and 165.50 kJ·mol -1 for the second stage. These values are consistent with those reported for the diffusion of carbon in austenite-FCC in silicon steels. With these activation energies it was possible to predict the austenite formation degree with a better level of convergence when implementing the non-isothermal model.

Background: Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis., Objective: To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing-remitting multiple sclerosis patients., Methods: Our study included 204 patients treated for relapsing-remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan-Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors., Results: Relapsing-remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1-18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0., Conclusions: The favourable influence of disease-modifying therapies on long-term disability in relapsing-remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

Radiotherapy is a curative treatment for localized prostate cancer in its modalities of brachytherapy (BT) and external beam radiotherapy (EBRT). A temporary increase in prostate-specific antigen (PSA) values following a radiotherapy treatment coupled with a decrease without therapeutic intervention may happen in 30% of the patients. This phenomenon is known as PSA bounce and lacks prognostic effect in relation to tumor control. Additionally, it produces anxiety in the patient because of the fear of failure, and in the physicists due to the uncertainty about the state of the tumor. The etiology and pathogenesis are still unknown. Several factors associated with the tumor and the treatments have been evaluated in the studies which analyze this phenomenon, the age is the only observed factor with the highest consistency as a bounce predictor. The definition of biologic failure (BF)after EBRT or BT with or without androgenic deprivation (ADT) according to Phoenix criteria, which considers an increase of at least 2 ng/ml over PSA nadir, enables better taking the bounce phenomenon into account, although is not free from false BF that may affect to the relapse-free survival in patients with follow-up shorter than 3 years.

In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2 years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3 months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6 months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10 months (range 6-18 months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6 months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6 months after NTZ withdrawal.

Objective: This study aims to assess the response and safety of the treatment of multiple sclerosis (MS) episodes with high oral doses of methylprednisolone (MP) and to investigate the correlation between expanded disability status scale (EDSS) and MS functional composite (MSFC) during recovery from relapses., Method: Patients consecutively diagnosed of clinically defined MS with an episode of less than three weeks course were included. They were evaluated and treated with a single dose of 1,000 mg of MP for three days without oral tapering. Baseline EDSS and at least three MSFC scale measurements were available. Patients were scored with EDSS and MSFC before the treatment and after 1, 4 and 12 weeks. Adverse events were also recorded. Response to treatment was defined as the recovery of at least 1 point in the EDSS or the return to baseline EDSS., Results: Twenty one episodes in 20 patients were treated. Mean baseline EDSS was, 2.5; mean baseline z-score was, 0.15, and mean relapse duration was, 6.8 days. During relapse, mean EDSS worsened to 3.8 and mean z-score to -0.57. At week 1, 33.4% of relapses had responded to treatment, and at weeks 4 and 12, 85.7% had responded. Although mean EDSS and mean z-score had already improved at week 1, mean EDSS did not reach baseline value until week 4 and mean z-score until week 12. EDSS correlated significantly to MSFC in each evaluation as well as to scale changes related to relapse (p;0.05). No serious adverse events were seen., Discussion: Oral high-dose of MP is a safe and effective therapy for MS relapses. Both EDSS and MSFC were sensitive to changes related to relapses although the dynamics of recovery was different, providing complementary information.