A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.     

Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.     

Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer

Immunologic Research - The expression of major histocompatibility complex class I (MHC I) in tumor cells is regulated by interferon signaling, and it is an important factor in the efficacy of...     

Vermamoeba vermiformis in hospital network: a benefit for Aeromonas hydrophila

Parasitology Research - Aeromonas hydrophila, considered as an emerging pathogen, is increasingly involved in opportunistic human infections. This bacterium, mainly present in aquatic environments,...     

6,7-Dehydroroyleanone diterpene derived from Tetradenia riparia essential oil modulates IL-4/IL-12 release by macrophages that are infected with Leishmania amazonensis

Parasitology Research - The treatment of cutaneous leishmaniasis in associated with several adverse effects and therapeutic failure, resulting in patients’ abandonment of treatment. Research...     

On (scientific) integrity: conceptual clarification

The notion of “integrity” is currently quite common and broadly recognized as complex, mostly due to its recurring and diverse application in various distinct domains such as the physical, psychic or moral, the personal or professional, that of the human being or of the totality of beings. Nevertheless, its adjectivation imprints a specific meaning, as happens in the case of “scientific integrity”. This concept has been defined mostly by via negativa, by pointing out what goes against integrity, that is, through the identification of its infringements, which has also not facilitated the elaboration of an overarching and consensual code of scientific integrity. In this context, it is deemed necessary to clarify the notion of “integrity”, first etymologically, recovering the original meaning of the term, and then in a specifically conceptual way, through the identification of the various meanings with which the term can be legitimately used, particularly in the domain of scientific research and innovation. These two steps are fundamental and indispensable for a forthcoming attempt at systematizing the requirements of “scientific integrity”.     

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil

Aim

This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability.

Methods

‘Picual’, ‘Blanqueta’, ‘Sevillana’, ‘Habichuelero’, and ‘Chetoui’ olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells.

Results

Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. ‘Sevillana’ VOO had the highest total bioaccessibility (36%), followed by the ‘Picual’ (19%), ‘Chetoui’ (17%), ‘Habichuelero’ (10%), and ‘Blanqueta’ (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, ‘Chetoui’, and ‘Blanqueta’-BF having the highest radical DPPH scavenging capacity, and ‘Habichuelero’ and ‘Picual’-BF showing protective effects against the peroxyl radical measured by ORAC_FL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells.

Conclusions

Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.

     

Debating social egg freezing: arguments from phases of life

So-called “social egg freezing” allows a woman to retain the possibility of trying to have a child with her own oocytes later in life, even after having become infertile in the strict sense of the word (that is, infertile without assistance in reproduction).There is a debate about whether it is morally permissible at all, the extent to which it should be permitted legally or even supported, and whether it is ethically desirable. This paper contributes some thoughts to the issue of ethical desirability. More precisely it deals with the question of whether there is any valuable argument to be made on the basis of the idea of life phases and normative expectations related to them. So the question is: Is there a right time in life to have a child, and does this speak against or in favor of social freezing? This question is answered in three steps. First, I will give an overview of ethical arguments that are mostly put forward in favor or against the use of social egg freezing and show that and why the question of life phases should be taken into account. Second, I will sketch what I understand by phases of life, more precisely, what I understand by normatively conceptualized life stages, that are to be distinguished from other kinds of life phases, and how they relate to a good life. Third, I will present two arguments that rely on the idea of life stages and speak against social egg freezing. However, I will criticize them and instead show that from the perspective of life stages nothing speaks against using the technique within certain limits.     

Controlled trial of the impact of a BC adult mental health practice support program (AMHPSP) on primary health care professionals’ management of depression

Background

Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual.

Methods

From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP?a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients >?18?years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5?weeks and psychotherapy within 3?months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n =?23; control n =?13). The study was prematurely terminated at 6?months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6?months follow-up. Outcome collectors and assessors were blind to group assignment.

Results

One hundred-and-twenty-nine patients (intervention n =?72; control n =?57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6?months, time by treatment interaction, likelihood ratio test (LR) chi2(3)?=?7.96, p =?.047.

Conclusions

This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes?even in absence of mental health specialists availability.

Trial registration

#NCT01975948.