Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, has been associated with the transmission by the tick Amblyomma sculptum, and one of its main hosts, the capybara ...(Hydrochoerus hydrochaeris).
During 2015-2019, we captured capybaras and ticks in seven highly anthropic areas of São Paulo state (three endemic and four nonendemic for BSF) and in two natural areas of the Pantanal biome, all with established populations of capybaras.
The BSF-endemic areas were characterized by much higher tick burdens on both capybaras and in the environment, when compared to the BSF-nonendemic areas. Only two tick species (A. sculptum and Amblyomma dubitatum) were found in the anthropic areas; however, with a great predominance of A. sculptum (≈90% of all ticks) in the endemic areas, in contrast to a slight predominance of A. dubitatum (≈60%) in the nonendemic areas. Tick species richness was higher in the natural areas, where six species were found, albeit with a predominance of A. sculptum (≈95% of all ticks) and environmental tick burdens much lower than in the anthropic areas. The BSF-endemic areas were characterized by overgrowth populations of A. sculptum that were sustained chiefly by capybaras, and decreased populations of A. dubitatum. In contrast, the BSF-nonendemic areas with landscape similar to the endemic areas differed by having lower tick burdens and a slight predominance of A. dubitatum over A.sculptum, both sustained chiefly by capybaras. While multiple medium- to large-sized mammals have been incriminated as important hosts for A. sculptum in the natural areas, the capybara was the only important host for this tick in the anthropic areas.
The uneven distribution of R. rickettsii infection among A. sculptum populations in highly anthropic areas of São Paulo state could be related to the tick population size and its proportion to sympatric A. dubitatum populations.
Objective
To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”.
Design
A consensus committee of 55 international experts representing 25 ...international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development.
Methods
The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.
Results
The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions.
Conclusions
Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Acute myeloid leukemia (AML) is the most lethal form of leukemia. Standard anti-AML treatment remains almost unchanged for decades. Tingenone (TG) and 22-hydroxytingenone (22-HTG) are quinonemethide ...triterpenes found in the Amazonian plant Salacia impressifolia (Celastraceae), with cytotoxic properties in different histological types of cancer cells. In the present work, we investigated the anti-AML action mechanism of TG and 22-HTG in the AML HL-60 cell line. Both compounds exhibited potent cytotoxicity in a panel of cancer cell lines. Mechanistic studies found that TG and 22-HTG reduced cell growth and caused the externalization of phosphatidylserine, the fragmentation of internucleosomal DNA and the loss of mitochondrial transmembrane potential in HL-60 cells. In addition, pre-incubation with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, prevented TG- and 22-HTG-induced apoptosis, indicating cell death by apoptosis via a caspase-dependent pathway. The analysis of the RNA transcripts of several genes indicated the interruption of the cellular antioxidant system, including the downregulation of thioredoxin, as a target for TG and 22-HTG. The application of N-acetyl-cysteine, an antioxidant, completely prevented apoptosis induced by TG and 22-HTG, indicating activation of the apoptosis pathway mediated by oxidative stress. Moreover, TG and 22-HTG induced DNA double-strand break and phosphorylation of JNK2 (T183/Y185) and p38α (T180/Y182), and co-incubation with SP 600125 (JNK/SAPK inhibitor) and PD 169316 (p38 MAPK inhibitor) partially prevented apoptosis induced by TG and 22-HTG. Together, these data indicate that TG and 22-HTG are new candidate for anti-AML therapy targeting thioredoxin.
•TG and 22-HTG induce caspase-mediated apoptotic cell death.•TG and 22-HTG target oxidative stress through downregulation of thioredoxin.•TG and 22-HTG cause DNA damage.•TG and 22-HTG cause JNK/p38-mediated apoptosis.
Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is ...a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34
leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.
Two experiments to determine the crude protein (CP) requirement of Heros severus were performed. Five isocaloric (3,200 kcal kg−1 of digestible energy) diets containing five levels of CP (28, 32, 36, ...40, and 44%) were evaluated. In the first, 75 fingerlings were distributed among 15 aquaria (30 L). In the second experiment, 100 juveniles were distributed among 20 aquaria (50 L). A quadratic effect on weight gain, specific growth rate for weight and for length, feed intake, feed conversion, body proteins, body lipids, and ash content of fingerlings occurred with increasing dietary CP, with optimum values estimated at 41.86, 40.30, 40.97, 39.60, 43.55, 40.64, 37.77, and 37.50% of CP, respectively. A linear effect on protein efficiency ratio of fingerlings occurred with increasing dietary CP. A quadratic effect on weight gain, specific growth rate for weight, feed conversion, hepatosomatic index, and body lipids of the juveniles were observed with increasing dietary CP, with optimum values estimated at 37.03, 37.20, 38.40, 35.13, 38.78, and 34,74% of CP, respectively. A linear effect on feed intake, protein efficiency ratio, and viscerosomatic index of juveniles occurred with increasing dietary CP. Blood glucose and hematocrit had lower values in juveniles fed a low level of CP.
•Sodium and flavor enhancers addition probiotic Prato Cheese processing.•No effect on the probiotic count and gastrointestinal resistance.•Increased proteolysis, ACE-values, firmness, elasticity and ...lower relaxation times (T2).•Increased antioxidant activity in probiotic Prato cheese added of arginine and oregano extract.•Different effects in monounsaturated fatty acids and short-chain fatty acids levels.
Cheese is a suitable matrix to deliver probiotic strains but it contains a high amount of sodium. The effect of partial substitution of NaCl by KCl and the addition of flavor enhancers (l-arginine, yeast and oregano extract) on probiotic Prato cheese was investigated after 1, 30, and 60 d of refrigerated storage (immediately after manufacturing, and during ripening and storage). Microbiological (lactic acid bacteria and probiotic Lactobacillus casei 01 counts and survival under gastrointestinal conditions), physicochemical (pH, proteolysis, fatty acids), bioactivity (antioxidant effect and angiotensin I-converting enzyme inhibitory activity), rheological, and water mobility by means of time domain low-field nuclear magnetic resonance were investigated. Significant changes in probiotic survival were observed; however, the sodium reduction and the addition of flavor enhancers did not constitute an obstacle to L. casei 01 (>108 CFU/g) during storage. Slight changes were observed in proteolysis, bioactivity, water mobility, texture profile, and fatty acids of the cheeses as a function of the flavor enhancer added. The sodium reduction and the supplementation of Prato cheese with probiotic cultures may be an effective alternative to the production of a potentially functional cheese.
Aquatic exercise is being increasingly recommended for healthy individuals as well as people with some special health conditions. A systematic review with meta‐analysis was performed to synthesize ...and analyze data on the effects of water‐based training (WT) programs on health status and physical fitness of healthy adults and adults with diseases to develop useful recommendations for health and sports professionals. We searched three databases (PubMed, Web of Science, and Scopus) up to June 2021 for randomized trials that examined WT in adults. A total of 62 studies were included, of which 26 involved only healthy individuals and 36 focused on adults with chronic diseases. In the healthy group, the effects of WT on strength, balance, and cardiorespiratory fitness were beneficial, indicating the usefulness of performing WT for at least 12 weeks (2–3x/week, 46–65 min/session). Among adults with diseases, improvements were observed in patients with fibromyalgia (in balance and cardiorespiratory fitness), bone diseases (pain, balance, flexibility, and strength), coronary artery disease (strength and anthropometry), hypertension (quality of life), stroke (quality of life), diabetes (balance and quality of life), multiple sclerosis (quality of life and balance), and Parkinson's disease (pain, gait, cardiorespiratory fitness, and quality of life). Research is required to determine the effects of WT on patients with heart disease, especially coronary artery disease. In adults with chronic disease, benefits in physical fitness and/or other health‐related measures were mainly observed after 8–16 weeks of training. WT is an effective physical activity when the intention is to enhance health and physical fitness in healthy adults and adults with chronic diseases.
Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as “ata”, “envira”, “envira-preta”, and ...“envira-surucucu”. In the present work, we investigated the in vitro and in vivo HepG2 cell growth inhibition capacity of D. pycnastera leaf essential oil (EO). The chemical composition of the EO was determined by GC−MS and GC−FID analyses. The alamar blue assay was used to examine the in vitro cytotoxicity of EO in cancer cell lines and non-cancerous cells. In EO-treated HepG2 cells, DNA fragmentation was measured by flow cytometry. The in vivo antitumor activity of the EO was assessed in C.B-17 SCID mice xenografted with HepG2 cells treated with the EO at a dosage of 40 mg/kg. Chemical composition analysis displayed the sesquiterpenes α-gurjunene (26.83%), bicyclogermacrene (24.90%), germacrene D (15.35%), and spathulenol (12.97%) as the main EO constituents. The EO exhibited cytotoxicity, with IC50 values ranging from 3.28 to 39.39 μg/mL in the cancer cell lines SCC4 and CAL27, respectively. The cytotoxic activity of the EO in non-cancerous cells revealed IC50 values of 16.57, 21.28, and >50 μg/mL for MRC-5, PBMC, and BJ cells, respectively. An increase of the fragmented DNA content was observed in EO-treated HepG2 cells. In vivo, EO displayed tumor mass inhibition activity by 47.76%. These findings imply that D. pycnastera leaf EO may have anti-liver cancer properties.
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