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

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

Mycorrhization of fagaceae forests within mediterranean ecosystems

Mediterranean Fagaceae forests are valuable due to their ecological and socioeconomic aspects. Some profitable plant species, such as Castanea (timber and chestnut), Quercus (timber and cork), and Fagus (timber), encounter in this habitat the excellent edaphoclimatic conditions to develop. All Fagaceae plants are commonly associated to ECM fungal species, which are found in these forests in quite stable communities, mainly enriched in Russulaceae and Telephoraceae species. Currently, the Mediterranean Basin is considered as one of the global biodiversity hotspots, since many of their endemic plant species are not found elsewhere and are now under threat. Due to climate changing and introduction of disease agents, Fagaceae forests are facing an adaptation challenge to both biotic and abiotic threats. Although ECM communities are highly disturbed by climate factors and tree disease incidence, they could play an important role in increasing water availability to the plant and also improving plant tree defense against pathogens. Recent advances, namely, on genomics and transcriptomics, are providing tools for increasing the understanding of Fagaceae mycorrhization process and stress responses to biotic and abiotic stresses. Such studies can provide new information for the implementation of the most adequate management policies for protecting threaten Mediterranean forests.info:eu-repo/semantics/publishedVersio

Prisão civil: Uma análise jurídica acerca da inviabilidade da aplicação do instituto à execução de alimentos destinados aos filhos maiores e capazes

A presente pesquisa tem como intuito analisar se a execução da verba alimentar destinada aos filhos maiores e capazes realizada sob o rito da prisão, se revela eficaz e adequada para atender aos interesses do alimentado sem obstaculizar os direitos do alimentante, considerando a natureza coercitiva da prisão, a ausência de risco à sobrevida do exequente e o princípio da menor onerosidade. Para tanto, foi analisada a  Lei Seca, especificamente, o atual Código Civil, e a legislação processual civil de 2015, bem como, a Constituição Federal de 1988 e as atuais jurisprudências acerca do tema, destacando-se as recentes decisões do Tribunal de Justiça de Minas Gerais. Trata-se de uma pesquisa qualitativa, descritiva e documental, cuja conclusão revela a inviabilidade da custódia civil nas execuções propostas por filho maior e capaz, por ferir o direito à liberdade do devedor sem que o adimplemento do débito exequendo se mostre essencial para  a sobrevivência do alimentando.

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

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

Quality of life according to type of confinement of Chilean university students during COVID-19 pandemic

Background: COVID-19 confinement measures in the population affected the quality of life and sleep. Aims: To determine if confinement is associated with a lower quality of life and sleep. Subjects and Methods: A self-reported survey including questions about type of confinement, time spent in front of a screen, the international physical activity questionnaire (IPAQ), the Sleep Self Report questionnaire and the SF-36 quality of life survey, was answered by 621 Chilean university students. Results: Confined and not confined respondents spent a great amount of time in front of a screen, in sedentary activities and sleeping > 8 or < 6 hours per day. Those who were in confinement reported having a poorer quality of sleep and quality of life compared to those who were not in confinement. Those who required mandatory confinement for suspected COVID-19 had the worst quality of sleep and quality of life. Conclusions: University students had sedentary lifestyles regardless of the type of confinement. Those who were in confinement, especially for suspected COVID-19 infection, had the worst quality of sleep and quality of life