Experiences, behaviours, and perspectives of young cancer survivors on physical activity.

This narrative review aimed to identify young cancer survivors' behaviours, experiences, and perspectives concerning physical activity, and identify useful strategies for promoting a healthy lifestyle. A manual search on the following databases was conducted: PubMed, Scopus, and Web of Science. The search was conducted between June 1, 2023, and April 12, 2024. Articles published from database inception up to April 12, 2024, were retrieved. Articles published in any language were considered. Perspectives including ideas, perceived barriers, and facilitators have been identified. Young cancer survivors seem to engage in physical activity as a useful coping strategy to regain normality and keep healthy after the cancer diagnosis. Although emotional and social support seems fundamental to increase participation, several other factors, including physical limitations, fatigue, sex, cancer type, and socio-economic status can influence physical activity participation. For those engaged in physical activity, the preferred activities are walking, biking, going to the gym, and exercising at home, while the least preferred are exercising at the hospital or boot camp-based exercises. Yoga is more frequently chosen by those still under treatment. Young cancer survivors appear to have unique needs different from those of adult cancer survivors. Mode of treatment delivery, increased awareness concerning the effects of physical activity, including families and friends, connecting survivors, and providing social support together with increasing motivation are key strategies for the promotion of physical activity in young cancer survivors. Fitness and healthcare professionals should consider these aspects to increase young cancer survivors' involvement in physical activities.

Interventions about physical activity and diet and their impact on adolescent and young adult cancer survivors: a Prisma systematic review.

PURPOSE: Over the past few decades, the incidence of cancer among adolescents and young adults (AYA) has been increasing. The impact of behaviors, such as physical activity (PA) and nutrition, on disease progression, prognosis, and overall health and quality of life for AYA cancer survivors is of significant importance. This systematic review aims to evaluate the effectiveness of PA and diet interventions for AYA cancer survivors and to critically evaluate existing literature, gaps, and limitations. METHODS: A search of literature was conducted in PubMed, Science Direct, Scopus, and Google Scholar following the PRISMA guidelines. Twenty-two studies were included from online databases from 2012 to 2022, 13 of which were randomized controlled trials. RESULTS: Most interventions were related to PA, with only four studies including nutrition or Diet interventions. The interventions were generally feasible and acceptable to AYA cancer survivors, and digitally based PA interventions were commonly used. PA interventions mainly comprised aerobic and resistance training and were individualized. Overall, this review found various PA and diet interventions for AYA cancer survivors that were feasible and well-accepted, but gaps in knowledge and design still exist. CONCLUSIONS: This systematic review underscores the importance of conducting more research on diet interventions for YCS. PROSPERO REGISTRATION: https://www.crd.york.ac.uk/prospero/#aboutregpage.

Effects of resistance training on sleep quality and disorders among individuals diagnosed with cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sleep disorders are often complained by cancer patients and can last years after the end of therapies, leading to different negative consequences. Non-pharmacological strategies such as exercise interventions may be considered to counteract this phenomenon. The literature supports the beneficial effects of aerobic training (AT), while evidence on resistance training (RT) is scarce. Accordingly, our systematic review aims to investigate the potential novel effect of RT on sleep outcomes in cancer survivors. METHODS: The literature search was conducted on MEDLINE (Pubmed), Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases, including only randomized controlled trials (RCTs). The screening procedure was conducted using the web-based software COVIDENCE. Sleep outcomes assessed through self-reported questionnaires or objective sleep measurements were extracted from RCTs recruiting cancer survivors of any age and gender, on or off treatment. The risk of bias (RoB) for each study was assessed using the Cochrane RoB 2 tool for RCTs. Meta-analytic syntheses were performed on sleep quality and insomnia. RESULTS: A total of 21 studies were included in the review. Considering the mean percentage differences of all studies combined, promising positive results were found after combined aerobic and resistance exercise program (COMB) for sleep quality (-19%) and sleep disturbance (-17.3%). The meta-analysis results showed significant improvement for both sleep quality and insomnia (d = 0.28, SE: 0.11, Z = 2.51, p < 0.01, 95% CI: 0.07-0.49 and d = 0.43, SE: 0.20, Z = 2.18, p = 0.029, 95% CI: 0.07-0.49, respectively). CONCLUSION: RT interventions of 60 minutes per session, performed 2-3 times a week for 12 weeks, with exercise intensity ranging from 60% to 80% of one-repetition maximum can be administered to cancer survivors, aiming to improve sleep outcomes.

One more rep! The case for resistance training in young cancer survivors.

Resistance training is now seen as a powerful tool to improve the health and functionality of cancer survivors. Literature shows that it can be implemented both during and after cancer treatment, with the intent of preserving muscle mass in the former and increasing muscle mass in the latter case. However, currently available data on this matter are predominantly derived from adult cancer survivors (ACS), and it is questionable whether the exact same raining regimen should be implemented in young cancer survivors (YCS) given the unique challenges they experience throughout their disease trajectory. Therefore, the goal of this work is to distill the existing evidence on resistance training (RT) interventions in ACS and facilitate discussion on whether the same patterns of RT can be applied in YCS.

Subversion strategies of lysosomal killing by intracellular pathogens.

Many pathogenic organisms need to reach either an intracellular compartment or the cytoplasm of a target cell for their survival, replication or immune system evasion. Intracellular pathogens frequently penetrate into the cell through the endocytic and phagocytic pathways (clathrin-mediated endocytosis, phagocytosis and macropinocytosis) that culminates in fusion with lysosomes. However, several mechanisms are triggered by pathogenic microorganisms - protozoan, bacteria, virus and fungus - to avoid destruction by lysosome fusion, such as rupture of the phagosome and thereby release into the cytoplasm, avoidance of autophagy, delaying in both phagolysosome biogenesis and phagosomal maturation and survival/replication inside the phagolysosome. Here we reviewed the main data dealing with phagosome maturation and evasion from lysosomal killing by different bacteria, protozoa, fungi and virus.

Estimating sequence diversity of prion protein gene (PRNP) in Portuguese populations of two cervid species: red deer and fallow deer.

Among the transmissible spongiform encephalopathies (TSEs), chronic wasting disease (CWD) in cervids is now a rising concern in wildlife within Europe, after the detection of the first case in Norway in 2016, in a wild reindeer and until June 2022 a total of 34 cases were described in Norway, Sweden and Finland. The definite diagnosis is post-mortem, performed in target areas of the brain and lymph nodes. Samples are first screened using a rapid test and, if positive, confirmed by immunohistochemistry and Western immunoblotting. The study of the genetics of the prion protein gene, PRNP, has been proved to be a valuable tool for determining the relative susceptibility to TSEs. In the present study, the exon 3 of PRNP gene of 143 samples from red deer (Cervus elaphus) and fallow deer (Dama dama) of Portugal was analysed. Three single nucleotide polymorphisms (SNPs) were found in red deer - codon A136A, codon T98A, codon Q226E - and no sequence variation was detected in fallow deer. The low genetic diversity found in our samples is compatible with previous studies in Europe. The comparison with results from North America suggests that the free-ranging deer from our study may present susceptibility to CWD, although lack of experimental data and the necessity of continuous survey are necessary to evaluate these populations.

Preoperative Location Of Parathyroid Adenomas In Primary Hyperparathyroidism: The Role of Cervical Doppler Ultrasound.

INTRODUCTION: Parathyroid adenoma is the most frequent cause of primary hyperparathyroidism. In recent years, the preoperative location of parathyroid adenomas allowed minimally invasive surgical techniques that have become preferred over the traditional bilateral neck exploration. The more recent guidelines on this subject highlight the role of nuclear medicine imaging tests. The aim of this study was to review the current role of Doppler ultrasound (US) in assessing the preoperative location of parathyroid adenomas in patients with primary hyperparathyroidism. MATERIAL AND METHODS: Retrospective study based on data from patients with primary hyperparathyroidism that underwent parathyroidectomy between January 2013 and January 2022 at the Centro Hospitalar Universitário Lisboa Central. Statistical analysis was performed with IBM SPSS Statistics, version 26.0.0.0®. RESULTS: Parathyroidectomy was performed in 171 patients (77.8% females) with primary hyperparathyroidism. Cervical Doppler ultrasound was the most performed test (64.3%, n = 110) for preoperative location and detected a suspicious lesion in 98 patients (89.1%). The preoperative location of the parathyroid adenomas was assessed through the Doppler ultrasound and was compared with the surgical reports and histological findings; a correct identification was made in 76 patients (77.6%). Doppler ultrasound slightly underestimated the mean adenoma size (18.1 ± 7.7 mm preoperative versus 22 ± 8.4 mm postoperative). Calcium, parathyroid hormone levels, adenoma size and concomitant presence of thyroid nodules did not affect the accuracy of Doppler ultrasound. CONCLUSION: Doppler ultrasound showed high diagnostic accuracy even in patients with nodular thyroid disease regardless of calcium and parathyroid hormone levels and adenoma size. Furthermore, its safety, affordability and availability should favor its use as first line test in primary hyperparathyroidism to assess the preoperative location of parathyroid adenomas.

Scrapie at Abattoir: Monitoring, Control, and Differential Diagnosis of Wasting Conditions during Meat Inspection.

Wasting disease in small ruminants is frequently detected at slaughterhouses. The wasting disorder is manifested by the deterioration of the nutritional and physiological state of the animal indicated by thinness, emaciation, and cachexia. Evidence of emaciation and cachexia, alone, are pathological conditions leading to carcass condemnation during an inspection. Several diseases are associated with a wasting condition, including scrapie, pseudotuberculosis, tuberculosis, paratuberculosis, Maedi Visna, and tumor diseases. On the other hand, parasitic diseases, nutrition disorders, exposure or ingestion of toxins, metabolic conditions, inadequate nutrition due to poor teeth, or poor alimentary diet are conditions contributing to poor body condition. Classical and atypical scrapie is naturally occurring transmissible spongiform encephalopathies in small ruminants. The etiological agent for each one is prions. However, each of these scrapie types is epidemiologically, pathologically, and biochemically different. Though atypical scrapie occurs at low incidence, it is consistently prevalent in the small ruminant population. Hence, it is advisable to include differential diagnosis of this disease, from other possibilities, as a cause of wasting conditions detected during meat inspection at the abattoir. This manuscript is a review of the measures in force at the abattoir for scrapie control, focusing on the differential diagnosis of gross lesions related to wasting conditions detected in small ruminants during meat inspection.

Circulation of Nor98 Atypical Scrapie in Portuguese Sheep Confirmed by Transmission of Isolates into Transgenic Ovine ARQ-PrP Mice.

Portugal was among the first European countries to report cases of Atypical Scrapie (ASc), the dominant form of Transmissible Spongiform Encephalopathy (TSE) in Portuguese small ruminants. Although the diagnostic phenotypes observed in Portuguese ASc cases seem identical to those described for Nor98, unequivocal identification requires TSE strain-typing using murine bioassays. In this regard, we initiated characterization of ASc isolates from sheep either homozygous for the ARQ genotype or the classical scrapie-resistant ARR genotype. Isolates from such genotypes were transmitted to TgshpXI mice expressing ovine PrPARQ. Mean incubation periods were 414 ± 58 and 483 ± 107 days in mice inoculated with AL141RQ/AF141RQ and AL141RR/AL141RR sheep isolates, respectively. Both isolates produced lesion profiles similar to French ASc Nor98 'discordant cases', where vacuolation was observed in the hippocampus (G6), cerebral cortex at the thalamus (G8) level, cerebellar white matter (W1) and cerebral peduncles (W3). Immunohistochemical PrPSc deposition was observed in the hippocampus, cerebellar cortex, cerebellar white matter and cerebral peduncles in the form of aggregates and fine granules. These findings were consistent with previously reported cases of ASc Nor98 transmitted to transgenic TgshpXI mice, confirming that the ASc strain present in Portuguese sheep corresponds to ASc Nor98.

Conservative idiopathic scoliosis treatment with brace produced using 3d technology / Tratamento da escoliose idiopática com colete produzido com tecnologia 3d / Tratamiento de la escoliosis idiopática con corsé producido con tecnología 3d

ABSTRACT Objective To evaluate the immediate correction capacity of the Wood-Chêneau-Rigo brace (WCR), produced using digital technological resources and robotic engineering, in primary and secondary curves of adolescent idiopathic scoliosis (AIS). Methods A retrospective study was conducted of 138 patients with a diagnosis of AIS and who received a WCR brace from a laboratory that makes orthoses and orthopedic prostheses between 2019 and 2021. These individuals were submitted to an independent analysis of the radiographic parameters by a single researcher, the main outcome of which was the standardized measurement of the main and secondary curves using the Cobb method. The radiographs analyzed were performed in orthostasis before and immediately after the adaptation of the brace on the patient. The correction capacity was calculated as the ratio of the difference between the pre- and post-brace curves to the pre-brace curve. Results The mean correction with the WCR was 48.4% for the main curve and 41.0% for the secondary curve. The level of correction of the main curve was significantly higher in patients with a main curve with the apex of convexity in the thoracolumbar region (p = 0.004), especially in the left thoracolumbar region (p = 0.010); curves of magnitude between 10º and 24.9º (p <0.001); and curves classified as simple (p <0.001). Conclusion The use of the WCR, which is produced using modern technological resources, was effective in the immediate correction of AIS. Long-term studies on this new modality of conservative scoliosis treatment are necessary. Level of evidence III; Retrospective study.

RESUMO Objetivo Avaliar a capacidade de correção imediata do colete Wood-Chêneau-Rigo (WCR), produzido com recursos tecnológicos digitais e de engenharia robótica, em curvas primárias e secundárias de escoliose idiopática do adolescente (EIA). Métodos Realizou-se um estudo retrospectivo com 138 pacientes com diagnóstico de EIA que adquiriram o colete WCR entre 2019 e 2021 em um laboratório de produção de órteses e próteses ortopédicas. Esses indivíduos foram submetidos à análise independente dos parâmetros radiográficos por um único pesquisador, tendo como desfecho principal a medida padronizada das curvas principal e secundária pelo método de Cobb. As radiografias analisadas foram realizadas em ortostase antes e imediatamente depois da adaptação do colete no paciente. A capacidade de correção foi calculada pela razão entre a diferença das curvas pré e pós-colete e a curva pré-colete. Resultados A média de correção da curva primária com o WCR foi de 48,4% e a da curva secundária foi de 41,0%. O nível de correção da curva primária foi significativamente maior nos pacientes com curva principal com ápice da convexidade na região toracolombar (p = 0,004), principalmente toracolombar à esquerda (p = 0,010); curvas com magnitude entre 10º e 24,9º (p < 0,001) e curvas do tipo simples (p < 0,001). Conclusões O colete WCR, produzido com modernos recursos tecnológicos, foi eficaz na correção imediata da EIA. São necessários estudos a longo prazo sobre essa nova modalidade de tratamento conservador da escoliose. Nível de Evidência III; Estudo retrospectivo.

RESUMEN Objetivo Evaluar la capacidad de corrección inmediata del corsé de Wood-Chêneau-Rigo (WCR), producido con recursos tecnológicos digitales e ingeniería robótica, en curvas primarias y secundarias de la escoliosis idiopática del adolescente (EIA). Métodos Se realizó un estudio retrospectivo de 138 pacientes con diagnóstico de EIA que adquirieron el corsé WCR entre 2019 y 2021 en un laboratorio de producción de ortesis y prótesis ortopédicas. Estos individuos fueron sometidos a un análisis independiente de los parámetros radiográficos por un solo investigador, siendo el resultado principal la medición estandarizada de las curvas principal y secundaria por el método de Cobb. Las radiografías analizadas se tomaron en bipedestación antes e inmediatamente después de la adaptación del corsé al paciente. La capacidad de corrección se calculó por la razón entre la diferencia entre las curvas de antes y de después del uso del corsé y la curva de antes del corsé. Resultados La corrección promedio de la curva primaria con el WCR fue del 48,4% y de la curva secundaria fue del 41,0%. El nivel de corrección de la curva primaria fue significativamente más grande en pacientes con una curva principal con vértice de la convexidad en la región toracolumbar (p = 0,004), principalmente toracolumbar a la izquierda (p = 0,010); curvas con magnitud entre 10º y 24,9º (p < 0,001) y curvas simples (p < 0,001). Conclusiones El uso corsé WCR, producido con modernos recursos tecnológicos, fue efectivo en la corrección inmediata de la EIA. Se necesitan estudios a largo plazo sobre esta nueva modalidad de tratamiento conservador de la escoliosis. Nivel de evidencia III; Estudio retrospectivo.

The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review.

(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4/5 seems to display contradictory and inconsistent conclusions.

Percepção de portadores de diabetes sobre educação em saúde e adoção de hábitos saudáveis / Perception of people with diabetes on health education and adoption of healthy habits

Este estudo teve como objetivo conhecer a percepção de portadores de Diabetes Mellitus Tipo 2 sobre a influência da educação em saúde para a adoção de hábitos saudáveis e o controle da doença. Trata-se de um estudo qualitativo fundamentado na Teoria da Representação Social. Os depoimentos de 23 entrevistados foram analisados por meio da técnica do Discurso do Sujeito Coletivo. Emergiram das respostas quatro Ideias Centrais a respeito das orientações de profissionais quanto aos hábitos saudáveis que podem contribuir para controle da doença, e seis que versaram acerca do modo como as ações educativas podem ser mais efetivas com vistas a estimular a adoção de um estilo de vida mais saudável. Com base nas representações dos participantes, este estudo trouxe a reflexão de que a educação em saúde, como recurso para incentivar a mudança de hábitos, só se torna efetiva quando fundamentada na realidade de cada indivíduo, envolvendo diálogo, escuta qualificada e capacitação para o autocuidado.

This study aimed to know the perception of Type 2 Diabetes Mellitus patients on the influence of health education for the adoption of healthy habits and disease control. The method used was a qualitative study based on Theory of Social Representation. The testimonies of 23 interviewees were analyzed using the Collective Subject Discourse technique. Four Central Ideas emerged from the testimonies on the guidelines of professionals regarding healthy habits that can contribute to disease control, and six that dealt with how educational actions can be more effective in stimulating the adoption of a healthier lifestyle. Based on the representations of the participants, this study brought the reflection that health education, as a resource to encourage the change of habits, only becomes effective when based on the reality of each individual, involving dialogue, qualified listening and training for the self-care.

Neuropathology of Animal Prion Diseases.

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

The prevalence and associated factors of nonadherence to antihypertensive medication in secondary healthcare.

PURPOSE: Non-adherence (NA) to medication is a major contributor to treatment failure in hypertensive patients. Factors of the ecological model, at family/healthcare professional, service, and system levels, are rarely evaluated as correlates of NA in hypertensive patients. METHODS: This crossectional study assessed the prevalence of and associated factors of NA to antihypertensive medication among 485 hypertensive patients upon receiving secondary healthcare. The Morisky Green Levine Scale (MGLS) measured the implementation phase of adherence, and the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA) instrument, health literacy. Multivariate analysis to NA included variables according to the levels of the ecological model. RESULTS: Most patients were female (56.3%), white (53.2%), mean age of 62.0 ± 12.6 years, illiterate (61.6%), with low health literacy (70.9%), and low income (65.4%). Uncontrolled BP was frequent (75.2%); 57.1% of patients were nonadherent. In multivariate analysis based on the ecological model, adjusted for micro, meso- and macro-level correlates, NA was associated only with variables of patient-level: low health literacy (OR 1.62, CI 1.07-2.44, p = 0.020), income ≥ two reference wages (OR 0.46, CI 0.22-0.93, p = 0.031), lack of homeownership (OR 1.99, CI 1.13-3.51, p = 0.017), sedentarism (OR 1.78, CI 1.12-2.83, p = 0.014), and complexity of treatment (number of medications taken ≥ two times/day) (OR 1.56, CI 1.01-2.41, p = 0.042). CONCLUSION: In this group of severely hypertensive patients with high cardiovascular risk, only patient-related characteristics were associated with NA. Our findings highlight the need for effective actions to optimize clinical outcomes in similar healthcare programs.

The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response.

Trypanosoma cruzi P21 protein (P21) is a putative secreted and immunomodulatory molecule with potent bioactive properties such as induction of phagocytosis and actin cytoskeleton polymerization. Despite the bioactive properties described so far, the action of P21 on parasite replication in muscle cell lineage or T. cruzi parasitism during acute experimental infection is unclear. We observed that recombinant P21 (rP21) decreased the multiplication of T. cruzi in C2C12 myoblasts, phenomenon associated with greater actin polymerization and IFN-γ and IL-4 higher expression. During experimental infection, lower cardiac nests, inflammatory infiltrate and fibrosis were observed in mice infected and treated with rP21. These results were correlated with large expression of IFN-γ counterbalanced by high levels of IL-10, which was consistent with the lower cardiac tissue injury found in these mice. We have also observed that upon stress, such as that induced by the presence of the IFN-γ cytokine, T. cruzi produced more P21. The effect of P21 in controlling the replication of T. cruzi, may indicate an evolutionary mechanism of survival developed by the parasite. Thus, when subjected to different stress conditions, the protozoan produces more P21, which induces T. cruzi latency in the host organism, enabling the protozoan to evade the host's immune system.

Human B cells infected by Trypanosoma cruzi undergo F-actin disruption and cell death via caspase-7 activation and cleavage of phospholipase Cgama1

B cells contribute to the immune system in many ways such as antigen presentation to CD4+ T cells, secretion of cytokines and lymphoid tissue organogenesis. Furthermore, they are the only cell type capable of producing immunoglobulins. B cells also account for critical aspects of the resistance against intracellular pathogens. Trypanosoma cruzi is an intracellular parasite that sabotages humoral response by depletion of immature B cells. Polyclonal activation and secretion of non-specific antibodies are also other mechanisms used by T cruzi to evade and subvert the mammalian host immune system, leading to increased parasitemia and susceptibility to Chagas’ disease. It remained unclear whether B cell depletion occurs due to direct contact with T. cruzi or results from a global increase in inflammation. Unlike previous reports, we demonstrated in this study that T. cruzi infects human B cells, resulting in parasite-induced activation of caspase-7 followed by proteolytic cleavage of phospholipase Cgama1 and cell death. These data contribute to explain the mechanisms ruling B-cell depletion and evasion of the immune response by T. cruzi.

Human B cells infected by Trypanosoma cruzi undergo F-actin disruption and cell death via caspase-7 activation and cleavage of phospholipase Cgama1

B cells contribute to the immune system in many ways such as antigen presentation to CD4+ T cells, secretion of cytokines and lymphoid tissue organogenesis. Furthermore, they are the only cell type capable of producing immunoglobulins. B cells also account for critical aspects of the resistance against intracellular pathogens. Trypanosoma cruzi is an intracellular parasite that sabotages humoral response by depletion of immature B cells. Polyclonal activation and secretion of non-specific antibodies are also other mechanisms used by T cruzi to evade and subvert the mammalian host immune system, leading to increased parasitemia and susceptibility to Chagas’ disease. It remained unclear whether B cell depletion occurs due to direct contact with T. cruzi or results from a global increase in inflammation. Unlike previous reports, we demonstrated in this study that T. cruzi infects human B cells, resulting in parasite-induced activation of caspase-7 followed by proteolytic cleavage of phospholipase Cgama1 and cell death. These data contribute to explain the mechanisms ruling B-cell depletion and evasion of the immune response by T. cruzi.

Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum.

Leprosy reactions are acute immunological events that occur during the evolution of chronic infectious disease causing neural damage and disabilities. A study using blood samples of 17 leprosy reaction patients and 17 reaction-free was carried out by means of associations between antigens, receptors, and expression of cytokines, using path analysis providing new insights into the immunological mechanisms involved in triggering leprosy reactions. Toll-like receptors (TLR) such as TLR1 and TLR2, presented balanced expression in the reaction-free multibacillary (MB) group (TLR1: 1.01 ± 0.23, TLR2: 1.22 ± 0.18; p = 0.267). On the other hand, downgrading type 1 reaction (T1R) (TLR1: 1.24 ± 0.17, TLR2: 2.88 ± 0.37; p = 0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93 ± 0.17, TLR2: 2.81 ± 0.15; p = 0.004) revealed an unbalance in relation to the expression of these receptors. When the path analysis was approached, it was noted that interleukin 10 (IL-10) expression showed a dependence relation with phenolic glycolipid I (PGL-I) in downgrading T1R (direct effect = 0.503 > residual effect = 0.364), whereas in ENL, such relationship occurred with lipoarabinomannan (LAM) (direct effect = 0.778 > residual effect = 0.280). On the contrary, in the reaction-free leprosy group, interferon-gamma (IFN-γ) levels were dependent on the association between TLR2 and TLR1 (0.8735). The high TLR2 expression associated with IL-10 levels, in the leprosy reaction groups, may be hypothetically related to the formation of TLR2/2 homodimers and/or TLR2/6 heterodimers linked to evasion mechanisms in downgrading reactions and pathophysiology of ENL.