Alveolar macrophages (AM) and monocytes (MO) are myeloid cells that play a substantial role in the development and establishment of the innate and adaptive immune response. These cells are crucial ...for host defense against various pathogens, but their role in malaria is poorly understood. Here, we characterize the dynamics of AMs and recruited leukocytes subpopulations in the airways during experimental Plasmodium berghei NK65-NY (PbNK65). We show that PbNK65 infection induces an increased pulmonary vascular permeability that provides Ly6Clow MOs, neutrophils (NEU), CD4+ and CD8+ lymphocytes in the airways. This inflammatory environment resulted in an increase in the population and alteration of the activation state of the AMs. Taken together, the data presented provide new insights into airway inflammation associated with pulmonary malaria.
Toxoplasma gondii chronic infection is characterized by the establishment of tissue cysts in the brain and increased levels of IFN-γ, which can lead to brain circuitry interference and consequently ...abnormal behaviour in mice. In this sense, the study presented here sought to investigate the impact of chronic infection by two T. gondii strains in the brain of infection-resistant mice, as a model for studying the involvement of chronic neuroinflammation with the development of behavioural alterations. For that, male BALB/c mice were divided into three groups: non-infected (Ni), infected with T. gondii ME49 clonal strain (ME49), and infected with TgCkBrRN2 atypical strain (CK2). Mice were monitored for 60 days to establish the chronic infection and then submitted to behavioural assessment. The enzyme-linked immunosorbent assay was used for measurement of specific IgG in the blood and levels of inflammatory cytokines and neurotrophic factors in the brain, and the cell's immunophenotype was determined by multiparametric flow cytometry. Mice infected with ME49 clonal strain displayed hyperlocomotor activity and memory deficit, although no signs of depressive- and/or anxiety-like behaviour were detected; on the other hand, chronic infection with CK2 atypical strain induced anxiety- and depressive-like behaviour. During chronic infection by CK2 atypical strain, mice displayed a higher number of T. gondii brain tissue cysts and inflammatory infiltrate, composed mainly of CD3+ T lymphocytes and Ly6Chi inflammatory monocytes, compared to mice infected with the ME49 clonal strain. Infected mice presented a marked decrease of microglia population compared to non-infected group. Chronic infection with CK2 strain produced elevated levels of IFN-γ and TNF-ɑ in the brain, decreased NGF levels in the prefrontal cortex and striatum, and altered levels of fractalkine (CX3CL1) in the prefrontal cortex and hippocampus. The persistent inflammation and the disturbance in the cerebral homeostasis may contribute to altered behaviour in mice, as the levels of IFN-γ were shown to be correlated with the behavioural parameters assessed here. Considering the high incidence and life-long persistence of T. gondii infection, this approach can be considered a suitable model for studying the impact of chronic infections in the brain and how it impacts in behavioural responses.
To establish clinical predictors of risk for decreased cardiac tissue perfusion (DCTP) after percutaneous coronary intervention (PCI).
Data on demographic, anthropometric, clinical, and procedural ...variables were collected as explanatory from a database of 1,542 adult patients undergoing PCI. A diagnosis of periprocedural myocardial infarction was used to confirm DCTP. A multivariate logistic regression determined the predictors of DCTP.
The independent predictors of risk for DCTP were age (OR = 1.02, CI 95% = 1.01-1.03, p = .008), multivessel disease (OR = 1.79, CI 95% = 1.30-2.46, p <.001) and intraprocedural lesion complications (OR = 4.56, CI 95% = 3.03-6.87, p <.001).
These results increase the level of evidence of risk for DCTP by refining its risk factors and can support nurses' clinical judgment.
Aims and objectives
To assess the clinical usefulness of the operational definitions for the defining characteristics of the NANDA International nursing diagnoses, activity intolerance, decreased ...cardiac output and excess fluid volume, and the concomitant presence of those diagnoses in patients with decompensated heart failure.
Background
Content validity of the operational definitions for the defining characteristics of activity intolerance, excess fluid volume and decreased cardiac output have been previously validated by experts. Their clinical usefulness requires clinical validation.
Design
This was a descriptive exploratory study.
Methods
Two expert nurses independently assessed 25 patients with decompensated heart failure for the presence or absence of 29 defining characteristics. Interrater reliability was analysed using the Kappa coefficient as a measure of clinical usefulness. The Fisher's exact test was used to test the association of the defining characteristics of activity intolerance and excess fluid volume in the presence of decreased cardiac output, and the correlation between the three diagnoses.
Results
Assessments regarding the presence of all defining characteristics reached 100% agreement, except with anxiety. Five defining characteristics of excess fluid volume were significantly associated with the presence of decreased cardiac output. Concomitant presence of the three diagnoses occurred in 80% of the patients. However, there was no significant correlation between the three diagnoses.
Conclusions
The operational definitions for the diagnoses had strong interrater reliability, therefore they were considered clinically useful. Only five defining characteristics were representative of the association between excess fluid volume and decreased cardiac output. Therefore, excess fluid volume is related to decreased cardiac output, although these diagnoses are not necessarily associated with activity intolerance.
Relevance to clinical practice
The operational definitions may favour early recognition of the sequence of responses to decompensation, guiding the choice of common interventions to improve or resolve excess fluid volume and decreased cardiac output.
The current outbreak of COVID-19 cases worldwide has been responsible for a significant number of deaths, especially in hospitalized patients suffering from comorbidities, such as obesity, diabetes, ...hypertension. The disease not only has prompted an interest in the pathophysiology, but also it has propelled a massive race to find new anti-SARS-CoV-2 drugs. In this scenario, known drugs commonly used to treat other diseases have been suggested as alternative or complementary therapeutics. Herein we propose the use of sitagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP
4
) used to treat type-II diabetes, as an agent to block and inhibit the activity of two proteases, 3CL
pro
and PL
pro
, related to the processing of SARS-CoV-2 structural proteins. Inhibition of these proteases may possibly reduce the viral load and infection on the host by hampering the synthesis of new viruses, thus promoting a better outcome. In silico assays consisting in the modeling of the ligand sitagliptin and evaluation of its capacity to interact with 3CL
pro
and PL
pro
through the prediction of the ligand bioactivity, molecular docking, overlapping of crystal structures, and molecular dynamic simulations were conducted. The experiments indicate that sitagliptin can interact and bind to both targets. However, this interaction seems to be stronger and more stable to 3CL
pro
(Δ
G
= −7.8 kcal mol
−1
), when compared to PL
pro
(Δ
G
= −7.5 kcal mol
−1
). This study suggests that sitagliptin may be suitable to treat COVID-19 patients, beyond its common use as an anti-diabetic medication. In vivo studies may further support this hypothesis.
Diagnostic tests for arachnid accidents remain unavailable for patients and clinicians. Together with snakes, these accidents are still a global medical concern, and are recognized as neglected ...tropical issues. Due to arachnid toxins' fast mechanism of action, quick detection and quantification of venom is required to accelerate treatment decisions, rationalize therapy, and reduce costs and patient risks. This review aims to understand the current limitations for arachnid venom identification and quantification in biological samples. We benchmarked the already existing initiatives regarding test requirements (sample or biomarkers of choice), performances (time, detection limit, sensitivity and specificity) and their validation (on animal models or on samples from envenomed humans). Our analysis outlines unmet needs for improving diagnosis and consequently treatment of arachnid accidents. Hence, based on lessons from past attempts, we propose a road map for raising best practice guidelines, leading to recommendations for future progress in the development of arachnid diagnostic assays.
Sphingomyelinases D (SMases D) or dermonecrotic toxins are well characterized in Loxosceles spider venoms and have been described in some strains of pathogenic microorganisms, such as Corynebacterium ...sp. After spider bites, the SMase D molecules cause skin necrosis and occasional severe systemic manifestations, such as acute renal failure. In this paper, we identified new SMase D amino acid sequences from various organisms belonging to 24 distinct genera, of which, 19 are new. These SMases D share a conserved active site and a C-terminal motif. We suggest that the C-terminal tail is responsible for stabilizing the entire internal structure of the SMase D Tim barrel and that it can be considered an SMase D hallmark in combination with the amino acid residues from the active site. Most of these enzyme sequences were discovered from fungi and the SMase D activity was experimentally confirmed in the fungus Aspergillus flavus. Because most of these novel SMases D are from organisms that are endowed with pathogenic properties similar to those evoked by these enzymes alone, they might be associated with their pathogenic mechanisms.
IL-17 is a cytokine produced by innate and acquired immunity cells that have an action against fungi and bacteria. However, its action in helminth infections is unclear, including in
Toxocara canis
...infection. Toxocariasis is a neglected zoonosis representing a significant public health problem with an estimated seroprevalence of 19% worldwide. In the present study, we describe the immunopathological action of IL-17RA in acute
T. canis
infection. C57BL/6j (WT) and IL-17RA receptor knockout (IL-17RA-/-) mice were infected with 1000
T. canis
eggs. Mice were evaluated 3 days post-infection for parasite load and white blood cell count. Lung tissue was harvested for histopathology and cytokine expression. In addition, we performed multiparametric flow cytometry in the BAL and peripheral blood, evaluating phenotypic and functional changes in myeloid and lymphoid populations. We showed that IL-17RA is essential to control larvae load in the lung; however, IL-17RA contributed to pulmonary inflammation, inducing inflammatory nodular aggregates formation and presented higher pulmonary IL-6 levels. The absence of IL-17RA was associated with a higher frequency of neutrophils as a source of IL-4 in BAL, while in the presence of IL-17RA, mice display a higher frequency of alveolar macrophages expressing the same cytokine. Taken together, this study indicates that neutrophils may be an important source of IL-4 in the lungs during
T. canis
infection. Furthermore, IL-17/IL-17RA axis is important to control parasite load, however, its presence triggers lung inflammation that can lead to tissue damage.
To identify and validate nursing diagnoses of elderly residents, and determine their relationship with the level of dependence in activities of daily living.
One hundred thirty-five older adults were ...assessed using medical history and physical examination. Twelve validated gerontological instruments were administered to assess delirium, nutritional status, risk for falls, risk for pressure injury, dementia, cognitive losses, depression, and level of dependence in daily living and instrumental activities of daily living. Nursing diagnoses were identified and validated by experienced, doctorally-prepared nurses. The association between the presence of a nursing diagnosis and the level of dependence was assessed by a test for trend in proportions. The Kruskal-Wallis hypothesis test was used to investigate the association between the number of nursing diagnoses and the level of dependence of the elderly.
Most older adults were at risk for malnutrition, at high risk for falls, cognitively impaired, totally dependent for daily living and activities of daily living. In addition, they had very mild dementia and most did not have risk for pressure injuries. Depression was noted among those with dementia, but was absent in those without dementia. A total of 52 nursing diagnoses were validated. Of these, 11 were associated with the level of dependence in daily living.
These results can be reproduced in other skilled nursing facilities for older adults, and these may allow the planning of interventions to alleviate etiologies and signs/symptoms of nursing diagnoses, rather than simply directing care toward a general category of dependence. Therefore, guaranteeing individualized nursing care to meet the specific needs of each resident.
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