Pathogens have developed particular strategies to infect and invade their hosts. Amongst these strategies' figures the modulation of several components of the innate immune system participating in ...early host defenses, such as the coagulation and complement cascades, as well as the fibrinolytic system. The components of the coagulation cascade and the fibrinolytic system have been proposed to be interfered during host invasion and tissue migration of bacteria, fungi, protozoa, and more recently, helminths. One of the components that has been proposed to facilitate pathogen migration is plasminogen (Plg), a protein found in the host's plasma, which is activated into plasmin (Plm), a serine protease that degrades fibrin networks and promotes degradation of extracellular matrix (ECM), aiding maintenance of homeostasis. However, pathogens possess Plg-binding proteins that can activate it, therefore taking advantage of the fibrin degradation to facilitate establishment in their hosts. Emergence of Plg-binding proteins appears to have occurred in diverse infectious agents along evolutionary history of host-pathogen relationships. The goal of the present review is to list, summarize, and analyze different examples of Plg-binding proteins used by infectious agents to invade and establish in their hosts. Emphasis was placed on mechanisms used by helminth parasites, particularly taeniid cestodes, where enolase has been identified as a major Plg-binding and activating protein. A new picture is starting to arise about how this glycolytic enzyme could acquire an entirely new role as modulator of the innate immune system in the context of the host-parasite relationship.
Flatworms are known for their remarkable regenerative ability, one which depends on totipotent cells known as germinative cells in cestodes. Depletion of germinative cells with hydroxyurea (HU) ...affects the regeneration of the parasite. Here, we studied the reduction and recovery of germinative cells in T. crassiceps cysticerci after HU treatment (25 mM and 40 mM of HU for 6 days) through in vitro assays. Viability and morphological changes were evaluated. The recovery of cysticerci’s mobility and morphology was evaluated at 3 and 6 days, after 6 days of treatment. The number of proliferative cells was evaluated using EdU. Our results show morphological changes in the size, shape, and number of evaginated cysticerci at the 40 mM dose. The mobility of cysticerci was lower after 6 days of HU treatment at both concentrations. On days 3 and 6 of recovery after 25 mM of HU treatment, a partial recovery of the proliferative cells was observed. Proteomic and Gene Ontology analyses identified modifications in protein groups related to DNA binding, DNA damage, glycolytic enzymes, cytoskeleton, skeletal muscle, and RNA binding.
The cyst stage of Entamoeba histolytica is a promising therapeutic target against human amoebiasis. Our research team previously reported the production in vitro of Cyst-Like Structures (CLS) sharing ...structural features with cysts, including rounded shape, size reduction, multinucleation, and the formation of a chitin wall coupled to the overexpression of glucosamine 6-phosphate isomerase, the rate-limiting enzyme of the chitin synthesis pathway. A proteomic study of E. histolytica trophozoites, cysts, and in vitro-produced CLS is reported herein to determine the nature of CLS, widen our knowledge on the cyst stage, and identify possible proteins and pathways involved in the encystment process. Total protein extracts were obtained from E. histolytica trophozoites, CLS, and partially purified cysts recovered from the feces of amoebic human patients; extracts were trypsin-digested and analyzed by LC-MS/MS. In total, 1029 proteins were identified in trophozoites, 550 in CLS, and 411 in cysts, with 539, 299, and 84 proteins unique to each sample, respectively, and only 74 proteins shared by all three stages. About 70% of CLS proteins were shared with trophozoites, even though differences were observed in the relative protein abundance. While trophozoites showed a greater abundance of proteins associated to a metabolically active cell, CLS showed higher expression of proteins related to proteolysis, redox homeostasis, and stress response. In addition, the expression of genes encoding for the cyst wall proteins Jessie and Jacob was detected by RT-PCR and the Jacob protein identified by Western blotting and immunofluorescence in CLS. However, the proteomic profile of cysts as determined by LC-MS/MS was very dissimilar to that of trophozoites and CLS, with almost 40% of hypothetical proteins. Our global results suggest that CLS are more alike to trophozoites than to cysts, and they could be generated as a rapid survival response of trophozoites to a stressful condition, which allows the parasite to survive temporarily inside a chitin-like resistant cover containing Jacob protein. Our findings lead us to suggest that encystment and CLS formation could be distinct stress responses. In addition, we show that cysts express a high number of genes with unknown function, including four new, highly antigenic, possibly membrane-located proteins that could be targets of therapeutic and diagnostic usefulness.
Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus ...itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31–61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs.
Key points
• ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity
• A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice
• Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice
Background: Inflammatory biomarkers are reportedly increased in depressed patients. Several studies have been conducted using neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and ...monocyte/lymphocyte ratio (MLR). The objective of this systematic review was to study the relationship between these peripheral biomarkers and suicidality in depressed patients with/without suicidal behavior, including suicide attempts and ideation, and healthy controls.Methods: We searched the following relevant terms in the PubMed, Web of Science, and Scopus databases published in the last five years. We assessed the methodological quality of included studies using the Oxford criteria and reviewed the evidence following PRISMA guidelines.Results: Eleven studies were retained for the data synthesis, with a total sample of 1,701 participants, of which the majority (819) were patients with depression and suicidal behavior, 494 were depressed patients without suicidal behavior, and only 388 were healthy participants. Our results reinforce the idea that NLR could be an attractive, convenient, and cost-effective trait marker of suicidal vulnerability in patients with major depressive disorder (MDD).Conclusion: Future large-scale replication studies are needed to examine the apparently understudied role of PLR and MLR in depressed patients in greater depth.
The potential impact of the COVID-19 pandemic on suicidal behavior has generated predictions anticipating an increase in suicidal tendencies. The aim of this research is to study its influence on the ...incidence of hospital-treated suicide attempts throughout the year 2020 in Oviedo, Spain.
Data were collected on all patients admitted to the emergency department of Central University Hospital of Asturias in Oviedo for attempted suicide during 2020. Incidence rates were calculated for three lockdown periods. Suicide attempt trends in 2020 were compared with a non-COVID-19 year (2009) to avoid seasonal variations bias. Chi-square and Fisher's exact tests were performed. The influence of COVID-19 incidence in Oviedo was analyzed using Spearman's correlation coefficient.
The cumulative incidence rate of attempted suicide per 100,000 person-years was 136.33 (pre-lockdown), 115.15 (lockdown), and 90.25 (post-lockdown) in adults (over 19 years old), and 43.63 (pre-lockdown), 32.72 (lockdown), and 72.72 (post-lockdown) in adolescents (10-19 years old). No association was found with COVID-19 incidence rates (Spearman's rho -0.222;
= 0.113). Comparing the years 2020 and 2009, statistically significant differences were observed in adolescents (Fisher's exact test;
= 0.024), but no differences were observed in adults (chi-square test = 3.0401;
= 0.218).
Hospital-treated suicide rates attempted during the COVID-19 outbreak in Oviedo, Spain showed a similar trend compared with a non-COVID-19 year. In contrast, the number of adolescents hospital-treated for attempted suicide increased during lockdown, suggesting more vulnerability to COVID-19 restrictions after the initial lockdown period in this age group.
Introduction
One of the great challenges still to be achieved in schizophrenia is the development of a staging model that reflects the progression of the disorder. The previous models suggested have ...been developed from a theoretical point of view and do not include objective variables such as biomarkers, physical comorbidities, or self-reported subjective variables (Martinez-Cao
et al.
Transl Psychiatry 2022; 12(1) 1-11).
Objectives
Develop a multidimensional staging model for schizophrenia based on empirical data.
Methods
Naturalistic, cross-sectional study. Sample: 212 stable patients with Schizophrenia (F20). Assessments:
ad hoc
questionnaire (demographic and clinical information); psychopathology: PANSS, CDS, OSQ, CGI-S; functioning: PSP; cognition: MATRICS; laboratory tests: C-Reactive Protein (CRP), IL-1RA, IL-6, Platelets/Lymphocytes (PLR), Neutrophils/Lymphocytes (NLR), and Monocytes/Lymphocytes (MLR) ratios. Statistical analysis: Variables selection was performed with an
ad hoc
algorithm developed for this research. The referred algorithm makes use of genetic algorithms (GA) to select those variables that show the best performance for the patients classification according to their global CGI-S. The objective function of the GA maximizes the individuals correct classification of a support vector machines (SVM) model that employs as input variables those given by the GA (Díez-Díaz
et al.
Mathematics 2021; 9(6) 654). Models performance was assessed with the help of 3-fold cross-validation and these process was repeated 10,000 times for each one of the models assessed.
Results
Mean age(SD): 39.5(13.54); men: 63.5%; secondary education: 59.50%. Most patients in our sample had never been married (74.10%), and more than a third received disability benefits due to schizophrenia (37.70%). The mean length of the disease was 11.98(12.02) years. The best SVM model included the following variables: 1)Clinical: number of hospitalizations, positive, negative, depressive symptoms and general psychopathology; 2)Cognition: speed of processing, visual learning and social cognition; 3)Functioning: PSP total score; 4)Biomarkers: PLR, NLR and MLR. This model was executed again 100,000 times applying again 3-fold cross-validation. In 95% of the algorithm executions more than a 53.52% of the patients were classfied in the right CGI-S category. On average the right classification was of 61.93%. About specificity and sensitivity the average values obtained were of 0.85 and 0.64 respectively.
Conclusions
Our staging model is a robust method that appropriately distributes patients according to the severity of the disorder. Highlights the importance of clinical, functional and cognitive factors to classify patients. Finally, the inflammatory parameters PLR, NLR and MLR have also emerged as potential biomarkers for staging schizophrenia.
Disclosure of Interest
None Declared
Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well ...as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood-brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover studies were conducted, which involved healthy male and female adult volunteers. After intranasal administration, DXM and MEP were detected in plasma after the first sampling time. Mean peak concentrations of DXM and MEP were 86.61 ng/mL at 60 min and 843.2 ng/mL at 1.5 h post-administration, respectively. DXM and MEP showed high absolute bioavailability, with values of 80% and 95%, respectively. No adverse effects were observed. DXM and MEP systemic bioavailability by intranasal administration was comparable with the intravenous one, suggesting that the intranasal route can be used as a non-invasive and appropriate alternative for systemic drug delivery.
Human cysticercosis by
is the major cause of neurological illness in countries of Africa, Southeast Asia, and the Americas. Publication of four cestode genomes (
,
,
and
) in the last decade, marked ...the advent of novel approaches on the study of the host-parasite molecular crosstalk for cestode parasites of importance for human and animal health.
is another cestode parasite, closely related to
, which has been used in numerous studies as an animal model for human cysticercosis. Therefore, characterization of the
genome will also contribute to the understanding of the human infection. Here, we report the genome of
WFU strain, reconstructed to a noncontiguous finished resolution and performed a genomic and differential expression comparison analysis against ORF strain. Both strain genomes were sequenced using Oxford Nanopore (MinION) and Illumina technologies, achieving high quality assemblies of about 107 Mb for both strains. Dotplot comparison between WFU and ORF demonstrated that both genomes were extremely similar. Additionally, karyotyping results for both strains failed to demonstrate a difference in chromosome composition. Therefore, our results strongly support the concept that the absence of scolex in the ORF strain of
was not the result of a chromosomal loss as proposed elsewhere. Instead, it appears to be the result of subtle and extensive differences in the regulation of gene expression. Analysis of variants between the two strains identified 2,487 sites with changes distributed in 31 of 65 scaffolds. The differential expression analysis revealed that genes related to development and morphogenesis in the ORF strain might be involved in the lack of scolex formation.
Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ...ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far.
We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts.
We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts.
Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality.
This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.
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