Do clinical and psychosocial factors affect health-related quality of life in adolescents with chronic diseases?

Copyright © 2006 - 2018 The Canadian Center of Science and Education. All Rights Reserved. Copyright for this article is retained by the author(s), with first publication rights granted to the journal. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).Living with a chronic disease in adolescence can have an impact on the perception of Health-related Quality of Life (HRQoL). Facing the increasing relevance of psychosocial dimensions and also considering the interaction with clinical variables, this study aimed to measure the impact of clinical and psychosocial factors (separated and combined) on adolescent’s reported HRQoL. A cross-sectional study was conducted in a clinical population of 135 adolescents with chronic diseases (n=70 boys), average age: 14±1.5 years old. Through a self-reported questionnaire, HRQoL (KIDSCREEN-10), socio-demographic, clinical variables (diagnostic; time of diagnosis; self-perceived pain; disease severity proxy; disease-related medication intake/use of special equipment), and psychosocial variables (psychosomatic health; resilience; self-regulation; social support) were assessed. Separately, clinical and psychosocial variables showed a significant impact in HRQoL, 27.9% and 62.4%, respectively. Once combined, the previously identified variables had a significant impact (64.2%), but a different contribution from clinical and psychosocial variables was revealed: when first entering the clinical variables (model 1) the variance only reaches 30%, and much more from psychosocial variables seems to explain the total (64.2%); inversely, when first integrating psychosocial variables (model 2), the clinical ones added a small significance to the model (0.6%). The present study underlined the association of clinical (“disease-related”) and psychosocial (“non-disease-related”) factors on HRQoL. Furthermore, it reinforced the need to focus more on psychosocial dimensions, highlighted the potential role of psychosomatic health, resilience, self-regulation and social support. It can be suggested that the identification of impaired psychosocial domains may help professionals to better plan, and achieve effective interventions of psychosocial care.Santos, T. was supported by a PhD grant from the Portuguese Foundation for Science and Technology (FCT) (Grant Number: reference SFRH/BD/82066/2011). The William James Center for Research, ISPA - Instituto Universitário is supported by a grant from the Portuguese Foundation for Science and Technology (FCT) (Grant Number: UID/PSI/04810/2013). The present study is grateful to all youngsters and parents who participated in this project, also to the health care professionals who collaborated, as well as to the Pediatrics Department of Hospital Santa Maria, CAML (Lisbon Academic Medical Center) for their assistance in this investigation. The authors are also grateful to Prof. Paula Ravasco, MD, PhD (University Hospital of Santa Maria, Portugal) for her assistance in proof-reading and revising the document.info:eu-repo/semantics/publishedVersio

Psychosocial profile in portuguese adolescents with chronic disease attending an outpatient department in a hospital setting

Living with a chronic disease (CD) in adolescence involves new multifaceted challenges. This study aims to conduct a psychosocial characterization of a group of adolescents with chronic diseases in a hospital setting and to compare such dimensions for the total group and for different diseases. A cross-sectional study included 135 adolescents with chronic diseases (51.9% boys; 48.1% girls), having an average age of 14±1.5 years (SD=1.5) and attending a paediatric outpatient department in a hospital setting. Statistically significant differences were found among the different chronic diseases for the variables self-regulation (adolescents with diabetes had significantly higher competencies) and multiple psychosomatic symptoms (adolescents with neurologic diseases reported significantly more complaints). Boys presented both better health-related quality of life and psychosomatic health when compared to girls. No statistically significant differences were observed for health-related quality of life, psychosomatic health, resilience, and social support. These findings bring important suggestions especially while planning interventions, which must take into account the promotion of a healthy psychosocial development, through an inclusive perspective (covering different chronic diseases), that take into consideration specific and gendered approaches. Such suggestions might help healthcare professionals to better plan interventions in order to increase their effectiveness.Fundação para a Ciência e a Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Dengue during pregnancy and live birth outcomes: a cohort of linked data from Brazil

OBJECTIVES: Dengue is the most common viral mosquito-borne disease, and women of reproductive age who live in or travel to endemic areas are at risk. Little is known about the effects of dengue during pregnancy on birth outcomes. The objective of this study is to examine the effect of maternal dengue severity on live birth outcomes. // DESIGN AND SETTING: We conducted a population-based cohort study using routinely collected Brazilian data from 2006 to 2012. // PARTICIPATING: We linked birth registration records and dengue registration records to identify women with and without dengue during pregnancy. Using multinomial logistic regression and Firth method, we estimated risk and ORs for preterm birth (<37 weeks' gestation), low birth weight (<2500 g) and small for gestational age (<10thcentile). We also investigated the effect of time between the onset of the disease and each outcome. // RESULTS: We included 16 738 000 live births. Dengue haemorrhagic fever was associated with preterm birth (OR=2.4; 95% CI 1.3 to 4.4) and low birth weight (OR=2.1; 95% CI 1.1 to 4.0), but there was no evidence of effect for small for gestational age (OR=2.1; 95% CI 0.4 to 12.2). The magnitude of the effects was higher in the acute disease period. // CONCLUSION: This study showed an increased risk of adverse birth outcomes in women with severe dengue during pregnancy. Medical intervention to mitigate maternal risk during severe acute dengue episodes may improve outcomes for infants born to exposed mothers

Diversity of HIV-1 Subtype B: Implications to the Origin of BF Recombinants

BACKGROUND: The HIV-1 subtype B epidemic in Brazil is peculiar because of the high frequency of isolates having the GWGR tetramer at V3 loop region. It has been suggested that GWGR is a distinct variant and less pathogenic than other subtype B isolates. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-four percent of the HIV-1 subtype B worldwide sequences (7689/8131) obtained from the Los Alamos HIV database contain proline at the tetramer of the V3 loop of the env gene (GPGR) and only 0.74% (60/8131) have tryptophan (GWGR). By contrast, 48.4% (161/333) of subtype B isolates from Brazil have proline, 30.6% (102/333) contain tryptophan and 10.5% (35/333) have phenylalanine (F) at the second position of the V3 loop tip. The proportion of tryptophan and phenylalanine in Brazilian isolates is much higher than in worldwide subtype B sequences (chi-square test, p = 0.0001). The combined proportion of proline, tryptophan and phenylalanine (GPGR+GWGR+GFGR) of Brazilian isolates corresponds to 89% of all amino acids in the V3 loop. Phylogenetic analysis revealed that almost all subtype B isolates in Brazil have a common origin regardless of their motif (GWGR, GPGR, GGGR, etc.) at the V3 tetramer. This shared ancestral origin was also observed in CRF28_BF and CRF29_BF in a genome region (free of recombination) derived from parental subtype B. These results imply that tryptophan substitution (e.g., GWGR-to-GxGR), which was previously associated with the change in the coreceptor usage within the host, also occurs at the population level. CONCLUSIONS/SIGNIFICANCE: Based on the current findings and previous study showing that tryptophan and phenylalanine in the V3 loop are related with coreceptor usage, we propose that tryptophan and phenylalanine in subtype B isolates in Brazil are kept by selective mechanisms due to the distinct coreceptor preferences in target cells of GWGR, GFGR and GFGR viruses

Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus

Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments

Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment

Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents diet- induced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a non- cleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment