Factors associated with health-related quality of life among children with cancer from the standpoint of patients and caregivers

Background

The quality of life for childhood cancer patients is impaired by this disease and its treatment. Knowing the factors that contribute most to this framework allows identifying the greatest needs, subsidized preventive strategies. The objective of the study was assessing the factors associated with health-related quality of life among children with cancer from the standpoint of patients and caregivers.

Methods

A cross-sectional study was conducted with sample consisted of 71 patients between the ages of 5 and 18 as well as their caregivers. Two forms (clinical examination and interview) from the National Oral Health Survey, the Modified Oral Assessment Guide and the Pediatric Quality of Life Inventory (PedsQLTM) version 3.0 were used as data collection instruments.

Results

From the standpoint of the caregivers, having fewer cognitive difficulties (OR?=?0.92), fewer pain symptoms and hurt (OR?=?0.94) and lower procedure anxiety (OR?=?0.93) were associated with higher quality of life scores; by contrast, being female (OR?=?9.49), the number of household members (OR?=?1.94) and smiling with embarrassment (OR?=?13.82) were associated with lower quality of life score. From the standpoint of patients, having fewer cognitive difficulties (OR?=?0.94) and positive perception of physical appearance (OR?=?0.94) were associated with higher quality of life scores; by contrast, smiling with embarrassment (OR?=?11.56) and toothaches (OR?=?7.37) were associated with lower quality of life score.

Conclusions

The patient and caregiver symptom reports yielded distinct results, although cognitive difficulties and smiling with embarrassment were significantly associated with impaired quality of life on both types of reports.

     

Rh antibodies as a result of altered Rh epitopes on transfused red cells: a case series of seven Brazilian patients

BackgroundRh antibodies produced by patients receiving Rh-matched RBC units may be associated with inheritance of altered RH alleles or a result of altered Rh epitopes on donor red blood cells (RBC). On this background, our aim was to evaluate unexpected Rh antibodies in Brazilian patients receiving regular transfusions and determine the clinical significance of the alloantibody produced.Material and methodsWe investigated seven patients (5 with sickle cell disease, 1 with myelodysplastic syndrome and 1 with β-thalassaemia) with unexplained Rh antibodies. All patients had complete serological and molecular analyses. A lookback at the donor units transfused to these patients was performed and donors suspected of having Rh variants were recruited for further analysis. Laboratory and clinical findings were used to evaluate the clinical significance of the alloantibodies produced.ResultsThe unexpected Rh antibodies found in the patients were not linked to the expression of partial Rh phenotypes according to serological and molecular analyses. Anti-D was found in two patients, anti-C was found in one patient, anti-c was found in one patient and anti-e was found in three patients carrying conventional D, C, c and e antigens respectively. Serological and molecular analyses of donors’ samples revealed that six donors whose RBC were transfused to these patients carried partial Rh antigens. Only one anti-e in a patient with β-thalassaemia was autoreactive and could not be explained by RH diversity in his donors. Three of the seven Rh antibodies were associated with laboratory and clinical evidence of a delayed haemolytic transfusion reaction or decreased survival of transfused RBC at first detection.DiscussionOur study provides evidence that patients exposed to RBC units from donors with Rh variants may develop antibodies and some of these may be of clinical significance.     

Eremantholide C from aerial parts of Lychnophora trichocarpha,as drug candidate: fraction absorbed prediction in humans and BCS permeability class determination

BackgroundLychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha.ObjectivesConsidering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process.MethodsIn situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 μg/ml, 96 μg/ml and 9.6 μg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions.ResultsEremantholide C showed P_eff values, in rats, greater than 5 × 10⁻⁵ cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the P_eff values for eremantholide C.ConclusionThe high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.Graphical abstract      

Neutrophil recruitment is inhibited by nicotinamide in experimental pleurisy in mice

Several emerging lines of evidence support an anti-inflammatory role for nicotinamide and other vitamin B components. However, the mechanisms underlying their activity remain unclear. In the present study, we investigated the ability of nicotinamide to inhibit both neutrophil recruitment in IL-8-, LTB(4)- or carrageenan-induced pleurisy in mice and the rolling and adherence of neutrophils. Nicotinamide inhibited IL-8-, LTB(4)- and carrageenan-induced neutrophil migration, KC production and carrageenan-induced neutrophil rolling and adherence. We propose that the effects of nicotinamide in inhibiting neutrophil recruitment in carrageenan-induced pleurisy may be due to the ability of nicotinamide to inhibit the action of IL-8 and LTB(4), decrease KC production, and inhibit early events that regulate leukocyte migration from blood vessels into tissue.     

Disability in multiple sclerosis is associated with age and inflammatory,metabolic and oxidative/nitrosative stress biomarkers: results of multivariate and machine learning procedures

The aim of this study was to evaluate the immune-inflammatory, metabolic, and nitro-oxidative stress (IM&NO) biomarkers as predictors of disability in multiple sclerosis (MS) patients. A total of 122 patients with MS were included; their disability was evaluated using the Expanded Disability Status Scale (EDSS) and IM&NO biomarkers were evaluated in peripheral blood samples. Patients with EDSS ≥3 were older and showed higher homocysteine, uric acid, advanced oxidized protein products (AOPP) and low-density lipoprotein (LDL)-cholesterol and higher rate of metabolic syndrome (MetS), while high-density lipoprotein (HDL)-cholesterol was lower than in patients with EDSS <3; 84.6% of all patients were correctly classified in these EDSS subgroups. We found that 36.3% of the variance in EDSS score was explained by age, Th17/T regulatory (Treg) and LDL/HDL ratios and homocysteine (all positively related) and body mass index (BMI) (inversely related). After adjusting for MS treatment modalities, the effects of the LDL/HDL and zTh17/Treg ratios, homocysteine and age on disability remained, whilst BMI was no longer significant. Moreover, carbonyl proteins were associated with increased disability. In conclusion, the results showed that an inflammatory Th17 profile coupled with age and increased carbonyl proteins were the most important variables associated with high disability followed at a distance by homocysteine, MetS and LDL/HDL ratio. These data underscore that IM&NO pathways play a key role in increased disability in MS patient and may be possible new targets for the treatment of these patients. Moreover, a panel of these laboratory biomarkers may be used to predict the disability in MS.

     

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740–751, 2019. © 2019 Wiley Periodicals, Inc.     

A comparative study on component volumes from outer to inner dental enamel in relation to enamel tufts

Background and aim

Dental enamel presents marked mechanical properties gradients from outer to inner enamel, a region lacking component volumes profiles. Tufts, structures of inner enamel, have been shown to play a role in enamel resilience. We aimed at comparing component volumes from inner to outer enamel in relation to enamel tufts.

Materials and methods

Transversal ground sections from the cervical half of unerupted human third molars (n = 10) were prepared and histological points were selected along transversal lines (extending from innermost to outer enamel) traced across tufts and adjacent control areas without tufts. Component volumes were measured at each histological point.

Results

Component volumes ranges were: 70.6–98.5% (mineral), 0.02–20.78% (organic), 3.8–9.8% (total water), 3–9% (firmly bound water), and 0.02–3.3% (loosely bound water). Inner enamel presented the lowest mineral volumes and the highest non-mineral volumes. Mineral, water and organic contents differed as a function of the distance from innermost enamel but not between the tuft and control lines. Tufts presented opaqueness in polarizing microscopy (feature of fracture lines). Organic volume gradient correlated with a relatively flat profile of loosely bound water. Inner, but not outer enamel, rehydrated after air-dried enamel was heated to 50 °C and re-exposed to room conditions, as predicted by the organic/water gradient profiles.

Conclusions

Component volumes vary markedly from outer to inner enamel, but not between areas with or without tufts (that behave like fracture lines under polarizing microscopy).