Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models

Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii and affects many individuals throughout the world. Infection may occur through congenital or acquired routes. The parasites enter the blood circulation and reach both the retina and the retinal pigment epithelium, where they may cause cell damage and cell death. Different routes of access are used by T. gondii to reach the retina through the retinal endothelium: by transmission inside leukocytes, as free parasites through a paracellular route, or after endothelial cell infection. A main feature of OT is the induction of an important inflammatory state, and the course of infection has been shown to be influenced by the host immunogenetics. On the other hand, there is evidence that the T. gondii phenotype also has an impact on the distribution of the pathology in different areas. Although considerable knowledge has been acquired on OT, a deeper knowledge of its mechanisms is necessary to provide new, more targeted treatment strategies. In particular, in addition to in vitro and in vivo experimental models, organotypic, ex vivo retinal explants may be useful in this direction

Energy reserves mobilization: Strategies of three decapod species

In food deprivation assays, several different responses have been observed in crustaceans. However, studying energy reserves utilization among more than one species during the same starvation period has not yet been performed, particularly to discern whether the responses are due to intrinsic and/or environmental factors. We hypothesize that decapod species with similar feeding habits have the same strategies in the use of energetic reserves during starvation, even though they inhabit different environments. The aim of this study was to compare the energy reserves mobilization of three decapods species (Cherax quadricarinatus, Palaemon argentinus and Munida gregaria) with similar feeding habits, exposed to similar food deprivation conditions. The crayfish, shrimp and squat-lobster were experimentally kept at continuous feeding or continuous starvation throughout 15 days. Every 3rd day, the midgut gland index (MGI), and the glycogen, lipid and protein contents were measured in the midgut gland (MG) and pleon muscle. Palaemon argentinus mobilized more reserves during starvation, followed by C. quadricarinatus, and the last M. gregaria. The starved shrimps presented low MGI, whereas MG showed a reduction in glycogen (from day 6 to 15), lipid (from day 3 to 15), and protein levels (at day 9 and 15) while in their muscle, lipid reserves decreased at days 3 and 6. In C. quadricarinatus, the most affected parameters in the MG were MGI, glycogen (from day 6 to 15), and lipids (at day 12 and 15). In the MG of M. gregaria only the glycogen was reduced during fasting from 3 to 15 days. Even though the three studied species have similar feeding habitats, we found that their energetic profile utilization is different and it could be explained by the habitat, life span, temperature, organ/tissue, and metabolism of the species. Our results may be useful to understand the several different responses of crustaceans during starvation.Fil: Sacristán, Hernán Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Rodriguez, Yamila Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pereira, Nair de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Lopez, Laura Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Lovrich, Gustavo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Fernandez Gimenez, Analia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

Exogenous proteases from seafood processing waste as functional additives in rainbow trout aquaculture

Previous studies about enzyme additives for salmonids employed commercial proteases from bacteria, but research obtaining such enzymes from other organisms are scarce. We aimed to increase digestive protease activity in Oncorhynchus mykiss, by analysing potential sources of exogenous proteases generated from different seafood processing waste. To date, there is no information regarding the influences that exogenous enzymes have on the activity and integrity of endogenous enzymes in salmonids. The compatibility and interaction between endogenous and exogenous proteases were evaluated through protein hydrolysis and electrophoresis. We also evaluated the capacity of two types of microcapsules (Alginate–Chitosan and Alginate–Chitosan–Bentonite) to protect the protease activity after being exposed to the gastric environment of trout. The seafood wastes had activities around 0.23–2.53 U/ml at 15°C. Among all the exogenous proteases evaluated, P. granulosa's extract showed the best performance, followed by L. santolla's extract. Such extracts increased the protein hydrolysis to equal or higher levels than the commercial protease and did not alter the integrity of trout proteases. The optimal catalytic function at low temperatures of these extracts might be linked to the habitat of these arthropods. Alginate–Chitosan–Bentonite microcapsules are recommended in preference to Alginate–Chitosan capsules for delivery of enzymes in salmonids because they ensure the activity of exogenous proteases for longer in acid pH (6 vs. 4 h). This research promotes a re-evaluation of seafood processing wastes through the production of a potentially functional additive that may improve trout protein digestion.Fil: Rodriguez, Yamila Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pereira, Nair de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Laitano, María V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Moreno, Pablo. Provincia del Neuquén. Subsecretaría de Producción y Recursos Naturales. Centro de Ecología Aplicada del Neuquén; ArgentinaFil: Fernandez Gimenez, Analia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

Characterization of liquid protein hydrolysates shrimp industry waste: Analysis of antioxidant and microbiological activity, and shelf life of final product

Proteases from shrimp wastes were characterized and protein hydrolysates were obtained. Shrimp protein hydrolysates (SPH) were produced by autolysis (H0) and added 1% (H1) and 2% vol/vol (H2) enzyme extract of shrimp. The hydrolysis degree was determined using a colorimetric method; the capability of hydrolysates to scavenge free radicals was measured with DPPH, and the antimicrobial activity of the SPH was evaluated by the microdilution test. The degree of protein hydrolysis ranged between 43% (H0) and 71.5% (H2) after 90 min, and it functioned as a source of lysine, leucine, aspartic acid, glutamic acid, and glycine. After 10 min of reaction, all hydrolysates reached 50% of scavenging effect. In addition, the SPH prepared with food additives showed acceptable microbiological quality and pH during 40 days at room temperature. This study aims at introducing a low-cost process which produces SPH with commercial applications in the food industry. Practical applications: Currently, shrimp processing wastes represents an environmental and economic problem, since such seafood industry must pay for the landfarming service. This waste treatment is not environmentally efficient, and it affects the value of the final product. However, these wastes have a large number of compounds which hold biological activities of interest that can be used to obtain a high added value product such as protein hydrolysates. This by-product has several potential applications for the food and pharmaceutical industries. In this study, a protein hydrolysate solution was obtained utilizing processed shrimp waste as an enzymatic resource and a protein substrate as well. This research demonstrated the feasibility of obtaining a good protein source that also holds useful antioxidant properties. It is important to highlight that the by-product was obtained without resorting to freeze-drying technology, which makes the industrial process more expensive. To accomplish that, we included low-cost food preservatives and assessed the shelf life of this product of high nutritional quality.Fil: Pereira, Nair de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Fangio, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; ArgentinaFil: Rodriguez, Yamila Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Bonadero, María Cecilia. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Haran, Nora Selma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Fernandez Gimenez, Analia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

The multikinase inhibitor EC‐70124 synergistically increased the antitumor activity of doxorubicin in sarcomas

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases. Therefore, we studied the antitumor activity of EC-70124, an indolocarbazole analog that have demonstrated a robust ability to inhibit a wide range of pro-survival kinases. Evaluation of the phospho-kinase profile in cell-of-origin sarcoma models and/or sarcoma primary cell lines evidenced that PI3K/AKT/mTOR, JAK/STAT or SRC were among the most highly activated pathways. In striking contrast with the structurally related drug midostaurin, EC-70124 efficiently prevented the phosphorylation of these targets and robustly inhibited proliferation through a mechanism associated to the induction of DNA damage, cell cycle arrest and apoptosis. In addition, EC-70124 was able to partially reduce tumor growth in vivo. Importantly, this compound inhibited the expression and activity of ABC efflux pumps involved in drug resistance. In line with this ability, we found that the combined treatment of EC-70124 with doxorubicin resulted in a synergistic cytotoxic effect in vitro and an increased antitumor activity of this cytotoxic drug in vivo. Altogether, these results uncover the capability of the novel multikinase inhibitor EC-70124 to counteract drug resistance in sarcoma and highlight its therapeutic potential when combined with current treatmentsPeer ReviewedPostprint (author's final draft

The Prevalence of Fatigue Following Deep Brain Stimulation Surgery in Parkinson's Disease and Association with Quality of Life

Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group. CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient\u27s outcomes. In that regard, CUP patients’ outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis. The biology of CUP has two main hypotheses. One is that CUP is a subgroup of a given primary cancer, where the primary is present but cannot be seen due to its small size. The other, the “true” CUP hypothesis, states that CUP share features that make them a specific entity, whatever their tissue of origin. A true biological signature has not yet been described, but chromosomal instability is a hallmark of poor prognosis CUP group. Precision oncology, despite achieving identifying the putative origin of the CUP, so far failed to globally improve outcomes of patients. Targeting molecular pathways based on molecular analysis in CUP management is under investigation. Immunotherapy has not shown ground-breaking results, to date. Accrual is also a crucial issue in CUP trials. Herein we review CUP history, biological features and remaining questions in CUP biology, the two main approaches of molecular oncology in CUP management, in order to draw perspectives in the enormous challenge of improving CUP patient outcomes

Peatlands of Southern South America : a review

This article is an outcome of the workshop entitled “Turberas: puesta al día y desafíos” (14 Jun 2017). The workshop was supported by FONDECYT Grant N° 11150275 from the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT). L.D.F. is funded by ANID (FONDECYT 11170927). We are very grateful to the reviewers and Dr Stephan Glatzel for their constructive suggestions.Peer reviewedPublisher PD

Klebsiella pneumoniae ST258 Negatively Regulates the Oxidative Burst in Human Neutrophils

The epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections

Emotional Processing Profile in Patients with First Episode Schizophrenia:The Influence of Neurocognition

This study sought to investigate the influence of neurocognition on the emotional processing profiles of patients with first-episode schizophrenia, using the 4-branch Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) (Perceiving Emotions; Facilitating Emotions; Understanding Emotions and Managing Emotions). A sample of 78 patients with first-episode schizophrenia and a group of 90 non-psychiatric control subjects were included in this work. The initial results showed that patients had lower scores than controls for the "Understanding Emotions" and "Managing Emotions" MSCEIT branches. However, after controlling for neurocognition, the only deficits were found on the "Managing Emotions" branch of the MSCEIT. This branch can be considered as measuring a more sophisticated level of emotional processing, which may constitute a deficit in itself. In conclusion, patients with first-episode schizophrenia present deficits in social cognition at the highest level that seem to be independent from neurocognition. These findings support the inclusion of the "Managing Emotions" branch of the MSCEIT as part of the MCCB.Instituto de Salud Carlos III (PI16/00359)Instituto de Salud Carlos III (PI19/00766)Comunidad de Madrid (S2017/BMD-3740)Ministry of Health (MOH-000013)4.242 JCR (2020) Q1, 39/167 Medicine, general & internal1.040 SJR (2021) Q1, 438/2489 Medicine (miscellaneous)No data IDR 2020UE