Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle.

It is controversial whether mitochondrial dysfunction in skeletal muscle is the cause or consequence of metabolic disorders. Herein, we demonstrate that in vivo inhibition of mitochondrial ATP synthase in muscle alters whole-body lipid homeostasis. Mice with restrained mitochondrial ATP synthase activity presented intrafiber lipid droplets, dysregulation of acyl-glycerides, and higher visceral adipose tissue deposits, poising these animals to insulin resistance. This mitochondrial energy crisis increases lactate production, prevents fatty acid ß-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle accumulation of acetyl-CoA leads to acetylation-dependent inhibition of mitochondrial respiratory complex II enhancing oxidative phosphorylation dysfunction which results in augmented ROS production. By screening 702 FDA-approved drugs, we identified edaravone as a potent mitochondrial antioxidant and enhancer. Edaravone administration restored ROS and lipid homeostasis in skeletal muscle and reinstated insulin sensitivity. Our results suggest that muscular mitochondrial perturbations are causative of metabolic disorders and that edaravone is a potential treatment for these diseases.

MicroRNA-124-3p Modulates Alpha-Synuclein Expression Levels in a Paraquat-Induced in vivo Model for Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD. In particular, miR-124 is downregulated in the plasma and brain samples of PD patients. Recently we showed that the brain delivery of miR-124 counteracts 6-hydroxydopamine-induced motor deficits. However, its role in α-synuclein pathology has never been addressed. Here we used paraquat (PQ)-induced rat PD model to evaluate the role of miR-124-3p in α-synuclein accumulation and dopaminergic neuroprotection. Our results showed that an intranigral administration of miR-124-3p reduced the expression and aggregation of α-synuclein in the substantia nigra (SN) of rats exposed to PQ. NADPH oxidases (NOX), responsible for reactive oxygen species generation, have been considered major players in the development of α-synuclein pathology. Accordingly, miR-124-3p decreased protein expression levels of NOX1 and its activator, small GTPase Rac1, in the SN of PQ-lesioned rats. Moreover, miR-124-3p was able to counteract the reduced levels of pituitary homeobox 3 (PITX3), a protein required for the dopaminergic phenotype, induced by PQ in the SN. This is the first study showing that miR-124-3p decreases PQ-induced α-synuclein levels and the associated NOX1/Rac1 signaling pathway, and impacts PITX3 protein levels, supporting the potential of miR-124-3p as a disease-modifying agent for PD and related α-synucleinopathies.

Generation of mitochondrial reactive oxygen species is controlled by ATPase inhibitory factor 1 and regulates cognition.

The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling.

From Grief to Growth: The Role of Coping Strategies, Kinship and Cause of Death.

Background: Research has predominantly focused on the post-traumatic consequences of grief. Less is known about the factors associated with the capacity for recovery and growth. Objective: The main goal of this study is to analyse the mediating role of coping strategies in the relationship between the impact of the event and posttraumatic growth, considering the degree of kinship and the cause of death. Methods: This exploratory and correlational study, which used a cross-sectional design, involved a community sample of 889 adults who had lost a loved one. Results: Emotion and problem-focused coping strategies mediate the relationship between the impact of loss and posttraumatic growth, specifically when a spouse or a child dies. Conclusions: Individuals who experience greater suffering also undergo higher levels of post-traumatic growth. Coping strategies are crucial in post-trauma reconstruction and growth. Furthermore, the degree of kinship and the cause of death are decisive factors.

Effect of Processing Methods of Human Saliva on the Proteomic Profile and Protein-Mediated Biological Processes.

The use of saliva as a protein source prior to microbiological and biological assays requires previous processing. However, the effect of these processing methods on the proteomic profile of saliva has not been tested. Stimulated human saliva was collected from eight healthy volunteers. Non-processed saliva was compared with 0.22 µm filtered, 0.45 µm filtered, and pasteurized saliva, by liquid chromatography-mass spectrometry. Data are available via ProteomeXchange with identifier PXD039248. The effect of processed saliva on microbial adhesion was tested using bacterial and fungus species and in biological cell behavior using HaCaT immortalized human keratinocytes. Two hundred and seventy-eight proteins were identified in non-processed saliva, of which 54 proteins (≈19%) were exclusive. Saliva processing reduced identified proteins to 222 (≈80%) for the 0.22 µm group, 219 (≈79%) for the 0.45 µm group, and 201 (≈72%) for the pasteurized saliva, compared to non-processed saliva. The proteomic profile showed similar molecular functions and biological processes. The different saliva processing methods did not alter microbial adhesion (ANOVA, p > 0.05). Interestingly, pasteurized saliva reduced keratinocyte cell viability. Saliva processing methods tested reduced the proteomic profile diversity of saliva but maintained similar molecular functions and biological processes, not interfering with microbial adhesion and cell viability, except for pasteurization, which reduced cell viability.

Comprehensive phylogenomic time tree of bryophytes reveals deep relationships and uncovers gene incongruences in the last 500 million years of diversification.

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer.

BACKGROUND: While the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease. METHODS: Sequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study. RESULTS: Testing 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26-30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%). CONCLUSION: The rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

Hydrothermal Carbon Coating of an Activated Carbon-A New Adsorbent.

A new adsorbent material was prepared by coating an activated carbon with hydrothermal carbon obtained from sucrose. The material obtained has different properties from the sum of the properties of the activated carbon and the hydrothermal carbon, which shows that a new material was obtained. It has a high specific surface area (1051.9 m2 g-1) and is slightly more acidic than the starting activated carbon (p.z.c.-point of zero charge 8.71 vs. 9.09). The adsorptive properties of a commercial carbon (Norit RX-3 Extra) were improved over a wide pH and temperature range. The capacity values of the monolayer according to Langmuir's model reached 588 mg g-1 for the commercial product and 769 mg g-1 for the new adsorbent.

Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation.

BACKGROUND: The brain vasculature plays a pivotal role in the inflammatory process by modulating the interaction between blood cells and the neurovascular unit. Argonaute-2 (Ago2) has been suggested as essential for endothelial survival but its role in the brain vasculature or in the endothelial-glial crosstalk has not been addressed. Thus, our aim was to clarify the significance of Ago2 in the inflammatory responses elicited by these cell types. METHODS: Mouse primary cultures of brain endothelial cells, astrocytes and microglia were used to evaluate cellular responses to the modulation of Ago2. Exposure of microglia to endothelial cell-conditioned media was used to assess the potential for in vivo studies. Adult mice were injected intraperitoneally with lipopolysaccharide (LPS) (2 mg/kg) followed by three daily intraperitoneal injections of Ago2 (0.4 nM) to assess markers of endothelial disruption, glial reactivity and neuronal function. RESULTS: Herein, we demonstrated that LPS activation disturbed the integrity of adherens junctions and downregulated Ago2 in primary brain endothelial cells. Exogenous treatment recovered intracellular Ago2 above control levels and recuperated vascular endothelial-cadherin expression, while downregulating LPS-induced nitric oxide release. Primary astrocytes did not show a significant change in Ago2 levels or response to the modulation of the Ago2 system, although endogenous Ago2 was shown to be critical in the maintenance of tumor necrosis factor-α basal levels. LPS-activated primary microglia overexpressed Ago2, and Ago2 silencing contained the inflammatory response to some extent, preventing interleukin-6 and nitric oxide release. Moreover, the secretome of Ago2-modulated brain endothelial cells had a protective effect over microglia. The intraperitoneal injection of LPS impaired blood-brain barrier and neuronal function, while triggering inflammation, and the subsequent systemic administration of Ago2 reduced or normalized endothelial, glial and neuronal markers of LPS damage. This outcome likely resulted from the direct action of Ago2 over the brain endothelium, which reestablished glial and neuronal function. CONCLUSIONS: Ago2 could be regarded as a putative therapeutic agent, or target, in the recuperation of the neurovascular unit in inflammatory conditions.

Appraising the Costs of Genomic Testing for Histology-Independent Technologies: An Illustrative Example for NTRK Fusions.

OBJECTIVES: Histology-independent (HI) technologies are authorized for patients with advanced or metastatic cancer if they express a particular biomarker regardless of its position in the body. Although this represents an important advancement in cancer treatment, genomic testing to identify eligible individuals for HI technologies will require substantial investment and impact their cost-effectiveness. Estimating these costs is complicated by several issues, which affect not only the overall cost of testing but also the distribution of testing costs across tumor types. METHODS: Key issues that should be considered when evaluating the cost of genomic testing to identify those eligible for HI technologies are discussed. These issues are explored in illustrative analyses where costs of genomic testing for NTRK fusions in England for recently approved HI technologies are estimated. RESULTS: The prevalence of mutation, testing strategy adopted, and current testing provision affect the cost of identifying eligible patients. The illustrative analysis estimated the cost of RNA-based next-generation sequencing to identify 1 individual with an NTRK fusion ranged between £377 and £282 258. To improve cost-effectiveness, testing costs could be shared across multiple technologies. An estimated additional ∼4000 patients would need to be treated with other HI therapies for testing in patients with advanced or metastatic cancer to be cost-effective. CONCLUSIONS: The cost of testing to identify individuals eligible for HI technologies affect the drug's cost-effectiveness. The cost of testing across tumor types varies owing to heterogeneity in the mutation's prevalence and current testing provision. The cost-effectiveness of HI technologies may be improved if testing costs could be shared across multiple agents.

Lethal and sublethal effects of essential oils fromPiper capitarianumYunck andPiper krukoffiiYunck onPlutella xylostellaL.

Plutella xylostella (L.) is responsible for considerable vegetable crop losses in the metropolitan region of Manaus, Brazil. In recent decades, essential oils have been investigated as an alternative to synthetic insecticides. The genusPiperis widely distributed in Amazonia and essential oils from these plants have insecticidal properties. This study describes the chemical composition of the essential oils fromPiper capiterianumandPiper krukoffiias well as the lethal and sublethal effects onP. xylostella. The phytotoxicity of the oils on the host plant was also evaluated. Globulol was the major constituent of theP. krukoffiioil ando-cymene was the major constituent of theP. capitarianumoil. The oil fromP. capiterianumexhibited greater toxicity to larvae and eggs. This oil also presented greater repellant action, feeding deterrence and mild phytotoxicity to the host plant (Brassicae oleraceae). The findings suggest that this oil can be used in the preparation of a formulated insecticide for the management ofP. xylostellain different development phases. However, further studies are needed to evaluate the effect of this oil on crops under field conditions as well as non-target organisms and determine the cost-benefit ratio of a product formulated withP. capitarianumoil.

R-Ras1 and R-Ras2 Expression in Anatomical Regions and Cell Types of the Central Nervous System.

Since the optic nerve is one of the most myelinated tracts in the central nervous system (CNS), many myelin diseases affect the visual system. In this sense, our laboratory has recently reported that the GTPases R-Ras1 and R-Ras2 are essential for oligodendrocyte survival and maturation. Hypomyelination produced by the absence of one or both proteins triggers axonal degeneration and loss of visual and motor function. However, little is known about R-Ras specificity and other possible roles that they could play in the CNS. In this work, we describe how a lack of R-Ras1 and/or R-Ras2 could not be compensated by increased expression of the closely related R-Ras3 or classical Ras. We further studied R-Ras1 and R-Ras2 expression within different CNS anatomical regions, finding that both were more abundant in less-myelinated regions, suggesting their expression in non-oligodendroglial cells. Finally, using confocal immunostaining colocalization, we report for the first time that R-Ras2 is specifically expressed in neurons. Neither microglia nor astrocytes expressed R-Ras1 or R-Ras2. These results open a new avenue for the study of neuronal R-Ras2's contribution to the process of myelination.

Mapping the trends and impact of research collaboration between countries in oral implantology publications: A bibliometric analysis from 1999 to 2019.

STATEMENT OF PROBLEM: Scientific collaboration provides a suitable strategy for enhancing the exchange of knowledge and technological development. However, the impact of collaboration in oral implantology research between countries and how it has been influenced by the income status of the country has not been previously evaluated. PURPOSE: The purpose of this bibliometric analysis was to evaluate how collaboration between countries affected oral implant publications and whether patterns of collaboration differ depending on the country's income. MATERIAL AND METHODS: Articles were retrieved from 7 well-established journals whose scope included oral implantology at 5 time points (1999, 2004, 2009, 2014, and 2019). Data were extracted, and descriptive, bivariate, and multivariate logistic regression analyses were performed (α=.05). RESULTS: A total of 1944 articles were included; of which, 27.5% presented collaboration between countries. In 2009, 2014, and 2019, collaboration between countries was more likely to occur than at previous time points (P≤.005). Corresponding authors with a higher h-index (P<.05) and authors from Europe and North America (P<.001) were more likely to establish international connections. The possibility of collaboration between countries was higher for animal studies (P<.001) and for articles published by Clinical Oral Implants Research (P=.026). Collaborations between high-income and upper-middle- or lower-middle-income countries were more likely to happen in 2014 and 2019 (P<.05), as well as when the number of authors was higher (P=.015), compared with collaboration between high-income countries. With regard to the continent, European articles were less likely to have collaborations with upper-middle- or lower-middle-income countries (P<.001). CONCLUSIONS: The findings revealed that some parameters related to the study, authors, countries, and journals were statistically associated with the presence of collaboration between countries. However, the bibliometric parameters showed different trends when countries of different incomes established collaboration.

Industry support for dental implant research: A metatrend study of industry partnership in the development of new technologies.

STATEMENT OF PROBLEM: Industry needs scientific knowledge to develop new products and services, and their financial support to dental implant researchers translates into commercial products. Therefore, identifying the relevant factors for a successful industry partnership is important. PURPOSE: The purpose of this study was to provide a 20-year bibliometric overview of industry-sponsored studies in implant dentistry to identify possible factors involved in industry partnership motivations. MATERIAL AND METHODS: A hand search of 6 of the most established journals in the implant dentistry field was performed for articles published in 1999, 2004, 2009, 2014, and 2019. Information regarding the continent of origin of the corresponding author, interinstitute collaboration, type and topic of research, and the h-index of the corresponding author was recorded for each included article. Bivariate and multivariate logistic regression was used to determine statistical relationship between industry support and exploratory factors (α=.05). RESULTS: A 6% increase in the chance of industry investment was observed over the years (odds ratio [OD]=1.06; P<.001). Studies from North America (OD=4.87; P<.001) and Europe (OD=3.13; P<.001) were more likely to receive industry funding. Data also revealed a direct relationship between the increasing number of institutions involved in the study and the probability of industry funding (OD=1.21; P<.001). Animal studies (OD=2.26; P<.001) about surgical procedures and prosthodontic topics (OD=1.40; P=.044) stood out for having greater industry support. Researchers with an h-index between 31 and 40 were more likely to receive industry financial support (OD=2.46; P=.001). CONCLUSIONS: Industry support for dental implant research was closely aligned with the continent of origin, interinstitute collaboration, type and topic of research, and the h-index of the corresponding author.

Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis.

Melanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the BRAF mutation present in 40-60% of melanoma cases. BRAF-mutated melanomas are characterized by a higher aggressiveness and progression. Adjuvant targeted treatments, such as BRAF and MEK inhibitors, are added to surgical excision in BRAF-mutated metastatic melanomas to maximize treatment effectiveness. However, resistance remains the major therapeutic problem. Interest in natural products, like propolis, for therapeutic applications, has increased in the last years. Propolis healing proprieties offer great potential for the development of novel cancer drugs. As the activity of Portuguese propolis has never been studied in melanoma, we evaluated the antitumoral activity of propolis from Gerês (G18.EE) and its fractions (n-hexane, ethyl acetate (EtOAc), and n-butanol) in A375 and WM9 melanoma cell lines. Results from DPPH•/ABTS• radical scavenging assays indicated that the samples had relevant antioxidant activity, however, this was not confirmed in the cell models. G18.EE and its fractions decreased cell viability (SRB assay) and promoted ROS production (DHE/Mitotracker probes by flow cytometry), leading to activation of apoptotic signaling (expression of apoptosis markers). Our results suggest that the n-BuOH fraction has the potential to be explored in the pharmacological therapy of melanoma.

Absence of R-Ras1 and R-Ras2 causes mitochondrial alterations that trigger axonal degeneration in a hypomyelinating disease model.

Fast synaptic transmission in vertebrates is critically dependent on myelin for insulation and metabolic support. Myelin is produced by oligodendrocytes (OLs) that maintain multilayered membrane compartments that wrap around axonal fibers. Alterations in myelination can therefore lead to severe pathologies such as multiple sclerosis. Given that hypomyelination disorders have complex etiologies, reproducing clinical symptoms of myelin diseases from a neurological perspective in animal models has been difficult. We recently reported that R-Ras1-/- and/or R-Ras2-/- mice, which lack GTPases essential for OL survival and differentiation processes, present different degrees of hypomyelination in the central nervous system with a compounded hypomyelination in double knockout (DKO) mice. Here, we discovered that the loss of R-Ras1 and/or R-Ras2 function is associated with aberrant myelinated axons with increased numbers of mitochondria, and a disrupted mitochondrial respiration that leads to increased reactive oxygen species levels. Consequently, aberrant myelinated axons are thinner with cytoskeletal phosphorylation patterns typical of axonal degeneration processes, characteristic of myelin diseases. Although we observed different levels of hypomyelination in a single mutant mouse, the combined loss of function in DKO mice lead to a compromised axonal integrity, triggering the loss of visual function. Our findings demonstrate that the loss of R-Ras function reproduces several characteristics of hypomyelinating diseases, and we therefore propose that R-Ras1-/- and R-Ras2-/- neurological models are valuable approaches for the study of these myelin pathologies.

Uptake of pre-symptomatic testing for BRCA1 and BRCA2 is age, gender, offspring and time-dependent.

BACKGROUND: Genetic testing for BRCA1 and BRCA2 pathogenic variants (PVs) has been available in North West England since 1995. We assessed uptake of pre-symptomatic testing in 1564 families with PVs over a 24.5year follow-up (FU) period. METHODS: First-degree relatives (FDRs) in families with BRCA1 or BRCA2 PVs were eligible from date of index family report if unaffected by a relevant cancer and alive at report date. FDRs were censored as not having undergone a pre-symptomatic test at diagnosis of a relevant cancer, date of death, age 93 or 30/03/2019. Time to uptake of pre-symptomatic testing was assessed by Kaplan-Meier curves, by gender and children. RESULTS: 2554 male and 3115 female FDRs were eligible. Overall uptake was 775 (30.3%) in men and 1935 (62.1%) in women. This increased at 15 years to 33.6% and 67.9%, and continued to rise until 24 years (p<0.001). For women, the 29-year to 39-year age group had the highest uptake at 10 years FU (72.5%; p<0.01), whereas the 50-year to 59-year age group was highest in men (37.2%; p<0.01). Women <18 years at the time of familial variant identification had lower initial uptake, but this rose to >80% by 15 years. Uptake was higher in parous women (p<0.001) and in men with daughters (p<0.0001). CONCLUSION: Uptake of BRCA1/2 pre-symptomatic testing is age, gender and time-dependent, and higher in women with children and men with daughters.

Breast cancer post-surgical impact on women´s quality of life during chemotherapy treatment: A structural equation modelling approach.

OBJECTIVE: Breast cancer is an important public health problem that is increasing in incidence, being a stressor with a negative impact on women's quality of life. This study is focused on the evaluation of temporal precursors (one month before) of women's quality of life undergoing chemotherapy, considering post-surgical personal, clinical, cognitive and neuropsychophysiological factors, according to the Transactional Stress and Coping Model. METHODS: This longitudinal study included 112 patients with breast cancer. Data were collected in two different moments: before and during the adjuvant chemotherapy. Structural equation modelling was used to support a theoretically based model in which some antecedent factors impact patients' long-term quality of life through a set of mediators. RESULTS: The associations of breast symptoms, body image and sexual functioning with psychological distress and quality of life were totally mediated by illness perceptions, while the associations of working memory with psychological distress and quality of life were totally mediated by self-efficacy for coping. Patients with greater psychological distress showed higher levels of nadir cortisol. CONCLUSIONS: Results showed the importance of assessing patients' perceptions of their illness, prior to chemotherapy, as well as promoting more self-efficacy for coping, in order to improve women's emotional state and quality of life.

Early recognition of surgical patients with sepsis: Contribution of nursing records.

OBJECTIVE: This study aimed to analyze the contribution of nursing records to the early identification and management of sepsis in surgical patients at a university hospital. METHOD: This is a study with a quantitative, retrospective, descriptive, and correlational design. Data collection was performed through hospital information systems in the first semester of 2017 with the approval of the research ethics committee. We included 28 patients who met the inclusion criteria of the study. RESULTS: The analysis of the content of the records evidenced the development of the first signs of systemic inflammatory response syndrome (SIRS) and organ dysfunction until the fifth day of hospitalization in 19 patients (67.8%). Confirmation or hypothesis of sepsis diagnosis occurred until the 10th day of hospitalization in 15 patients (53.5%). The analysis of the content of the records showed that the first signs of SIRS were predominantly identified in the electronic patient monitoring system in 26 cases (92.9%), whereas the first signs of organ dysfunction were described in the nursing staff records in 24 patients (85.7%). CONCLUSION: The results confirm the importance of the quality of nursing records for risk identification, early recognition, and proper management of sepsis in surgical patients, aiming at achieving greater effectiveness in the management of healthcare processes.