Tumor suppressive role of the antimicrobial lectin REG3A targeting the O -GlcNAc glycosylation pathway.

BACKGROUND AND AIMS: Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) family provide a first line of protection against infections and transformed cells. Their expression is inducible by inflammation, which makes their role in cancer biology less clear since an immune-inflammatory context may preexist or coexist with cancer, as occurs in HCC. The aim of this study is to clarify the role of REG3A in liver carcinogenesis and to determine whether its carbohydrate-binding functions are involved. APPROACH AND RESULTS: This study provides evidence for a suppressive role of REG3A in HCC by reducing O -GlcNAcylation in 2 mouse models of HCC, in vitro cell studies, and clinical samples. REG3A expression in hepatocytes significantly reduced global O -GlcNAcylation and O -GlcNAcylation of c-MYC in preneoplastic and tumor livers and markedly inhibited HCC development in REG3A-c-MYC double transgenic mice and mice exposed to diethylnitrosamine. REG3A modified O -GlcNAcylation without altering the expression or activity of O-linked N-acetylglucosaminyltransferase, O-linked N-acetylglucosaminyl hydrolase, or glutamine fructose-6-phosphate amidotransferase. Reduced O -GlcNAcylation was consistent with decreased levels of UDP-GlcNAc in precancerous and cancerous livers. This effect was linked to the ability of REG3A to bind glucose and glucose-6 phosphate, suggested by a REG3A mutant unable to bind glucose and glucose-6 phosphate and alter O -GlcNAcylation. Importantly, patients with cirrhosis with high hepatic REG3A expression had lower levels of O -GlcNAcylation and longer cancer-free survival than REG3A-negative cirrhotic livers. CONCLUSIONS: REG3A helps fight liver cancer by reducing O -GlcNAcylation. This study suggests a new paradigm for the regulation of O -GlcNAc signaling in cancer-related pathways through interactions with the carbohydrate-binding function of REG3A.

Septin 9 expression regulates 'don't eat me' signals and identifies an immune-epithelial class of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and aggressive liver cancer with limited therapeutic options. Precise classification and immunotherapy are perspectives to improve the treatments. We reported the role of septin 9 in apico-basal polarity and epithelial-to-mesenchymal transition (EMT). Here, we aim to elucidate its role in iCCA. We analyzed single-cell transcriptomes from human iCCA tumor cells based on phenotype and cell state. Knockdown of the septin 9 gene (SEPT9) was done using small interfering RNA (siRNA); interferon-γ (IFN-γ) stimulation was performed using different CCA cells; gene expressions were analyzed by reverse transcription and real-time PCR analysis (RT-qPCR); and immunofluorescence, immunoblotting, and flow cytometry were performed to assess the expression of proteins. The differential distributions of SEPT9 and vimentin (VIM) gene expressions allowed us to define specific cellular trajectories of malignant cells and thus identified distinct clusters of iCCA cells. One cluster was enriched in VIM and extracellular-matrix (ECM) remodeling molecules, and another had high expression of SEPT9 and genes from the 'don't eat me' signal involved in immune escape. This antagonism between SEPT9 and VIM was confirmed by in vitro experiments. Notably, SEPT9 and 'don't eat me' gene expressions were inversely correlated to those of vimentin and the EMT markers. SEPT9 expression was upregulated by IFN-γ and SEPT9 knockdown decreased expression of 'don't eat me' signal genes and increased expression of mesenchymal markers. Cancer Cell Line Encyclopedia (CCLE) transcriptome database analyses confirmed that iCCA cells enriched in septin 9 exhibit epithelial-like features. This study revealed septin 9 as a cytoskeleton element of iCCA epithelial-like cells and a regulator of the immune system response. It also brings new insights into the enigmatic relationship between EMT and immune response. Notably, we decoded a potential mechanism that could sensitize patients to immunotherapies.

Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. METHODS: This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. RESULTS: Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. CONCLUSIONS: Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Ecological, Genetic, and Phylogenetic Aspects of YFV 2017-2019 Spread in Rio de Janeiro State.

In Brazil, a yellow fever (YF) outbreak was reported in areas considered YF-free for decades. The low vaccination coverage and the increasing forest fragmentation, with the wide distribution of vector mosquitoes, have been related to yellow fever virus (YFV) transmission beyond endemic areas since 2016. Aiming to elucidate the molecular and phylogenetic aspects of YFV spread on a local scale, we generated 43 new YFV genomes sampled from humans, non-human primates (NHP), and primarily, mosquitoes from highly heterogenic areas in 15 localities from Rio de Janeiro (RJ) state during the YFV 2016-2019 outbreak in southeast Brazil. Our analysis revealed that the genetic diversity and spatial distribution of the sylvatic transmission of YFV in RJ originated from at least two introductions and followed two chains of dissemination, here named the YFV RJ-I and YFV RJ-II clades. They moved with similar dispersal speeds from the north to the south of the RJ state in parallel directions, separated by the Serra do Mar Mountain chain, with YFV RJ-I invading the north coast of São Paulo state. The YFV RJ-I clade showed a more significant heterogeneity across the entire polyprotein. The YFV RJ-II clade, with only two amino acid polymorphisms, mapped at NS1 (I1086V), present only in mosquitoes at the same locality and NS4A (I2176V), shared by all YFV clade RJ-II, suggests a recent clustering of YFV isolates collected from different hosts. Our analyses strengthen the role of surveillance, genomic analyses of YVF isolated from other hosts, and environmental studies into the strategies to forecast, control, and prevent yellow fever outbreaks.

Incidence and Predictive Factors for Amputations Derived From Charcot's Neuroarthropathy in Persons With Diabetes.

Charcot's neuroarthropathy (CN) is the progressive destruction of the bones and joints of the feet, as a consequence of severe peripheral neuropathy, which predisposes patients to amputations. The purpose of this study was to measure the cumulative incidence of amputations resulting from CN and risk factors among amputated people with diabetes mellitus (DM). This was an epidemiological, observational, and retrospective study of 114 patients with DM who had an amputation involving the lower limbs. Data were collected from 2 specialized outpatient clinics between 2015 and 2019, including socio-demographic and clinical variables (cause of amputation: CN, peripheral arterial disease [PAD], infected ulcers, fracture, osteomyelitis, and others; body mass index [BMI]; 1 or 2 DM, time since DM diagnosis, insulin treatment, glycated hemoglobin; creatinine; smoking and drinking; systemic arterial hypertension, diabetic retinopathy, diabetic kidney disease, diabetic peripheral neuropathy, acute myocardial infarction, PAD, and stroke; characteristics of amputation [level and laterality], in addition to the specific variables related to CN [time of amputation in relation to the diagnosis of CN, diagnosis of CN in the acute phase, and treatment implemented in the acute phase]). We compared socio-demographic and clinical characteristics, including types of amputation, between patients with and without CN. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson's χ2 test or Fisher's exact test for categorical variables. The investigation of the possible association of predictive factors for a CN amputation was carried out through logistic regression. The amputation caused by CN was present in 27 patients with a cumulative incidence of 23.7% in 5 years. There was a statistically significant association between BMI and the occurrence of CN (odds ratio: 1.083; 95% confidence interval: 1.001-1.173; P = .048); higher values of BMI were associated with a higher occurrence of amputations secondary from CN.

Anterior cruciate ligament arthroscopic reconstruction and lateral tenodesis with iliotibial band and gracilis tendon: Technical note.

While anterior cruciate ligament reconstruction using the iliotibial band is not a new technique, it still remains underdeveloped. The iliotibial band has historically been described as a thin and less resistant structure. Its harvesting has been associated with a risk of complications (hematoma, muscle hernia) and its small graft diameter increases the risk of rerupture. The addition of the gracilis tendon could potentially produce a graft with an increased diameter. In this technical note, we present a modification to the traditional technique performed on 50 patients, describing the surgical steps, graft diameter, clinical outcomes and complications at the 2-year follow-up. The mean graft diameter was 8.9±0.9 mm at the femur and 7.7±0.7 mm at the tibia. No rerupture was reported at the 2-year follow-up. LEVEL OF EVIDENCE: IV.

SARS-CoV-2 variant N. 9 identified in Rio de Janeiro, Brazil

BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.33-derived lineage named N.9 was described recently in Brazil and it's considered a potential variant of interest (VOI) due to the presence of E484K substitution at the receptor-binding domain (RBD) of the Spike (S) protein. OBJECTIVE To describe the first detection of variant N.9 in Rio de Janeiro State. METHODS SARS-CoV-2 N.9 was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), whole-genome sequencing and phylogenetic analysis. FINDINGS Here, we report two SARS-CoV-2 N.9 lineage strains in Rio de Janeiro. One of them had only the E484K substitution of the six N.9 lineage-defining mutations. Other three strains pre-defined as N.9 have the same genomic profile. These four strains are grouped within the B.1.1.33 lineage and basal to the N.9 lineage in our phylogenetic analysis, and we call them "N.9-like/B.1.1.33 + E484K". MAIN CONCLUSIONS The phylogenetic analysis shows four independent introductions of N.9 in the state of Rio de Janeiro in October and December 2020, January and March 2021. SARS-CoV-2 N.9 dissemination in the Rio de Janeiro could have been limited by the emergence and dominance of other variants, mainly by the lineage P.2 VOI Zeta that emerged in the same period and co-circulated with N.9, as observed in the neighboring State of São Paulo.

Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity.

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB). Brown, red or black melanin pigments can be produced by the polyketide pathway (DHN-melanin) or from dihydroxyphenols, such as L-DOPA (L-3,4-dihydroxyphenylalanine) and L-tyrosine by polyphenoloxidases. Among several pathogenic fungi, Cryptococcus neoformans is a melanized yeast that causes pneumonia and meningoencephalitis in immunocompromised patients. The knockout of the laccase genes or other interruptions on melanin biosynthetic pathway generates cryptococcal strains with attenuated virulence in an animal model. In this study 16 analogues of coumaric and cinnamic acid were evaluated as possible tyrosinase inhibitors. We have identified some valuable inhibitors of C. neoformans growth and melanin biosynthesis disruption agents. The results showed that coumaric acid derivatives (1a-c), the ketones (3a-b) and 2-allylphenol (7c) are significant inhibitors of tyrosinase and melanization of the fungus. Two analogues (1b and 3b) were selected as promising antimelanogenic agents to be combined with AmB, showing to promote 16-fold reduction in the AmB fungicidal concentration with no appreciable cytotoxicity to mammalian cells. The data suggest that inhibition of the melanin biosynthesis by these compounds may increase the susceptibility of the cells to the oxidative stress generated by AmB. In summary, our data show that C. neoformans can be a suitable model system to test novel inhibitors that target melanin biosynthesis, and novel compounds for adjunct therapy against C. neoformans were identified.

Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME-based classification of ICC tumors that detects potentially targetable ICC subtypes. APPROACH AND RESULTS: We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population-counter package and compared with immunohistochemistry. We performed an unsupervised TME-based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME-based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor-infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival. CONCLUSION: We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.

First inter-laboratory comparison of Echinococcus granulosus sensu lato diagnosis in Latin America.

OBJECTIVE: To compare the performance of polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) tests for diagnosing Echinococcus granulosus in dog feces among national reference laboratories in Argentina, Chile, Peru, and Uruguay. METHODS: National laboratories affiliated with the Ministry of Health/Agriculture of each country exchanged panels of 10 positive/negative samples obtained from their regular national surveillance programs in November 2015 - November 2016. All laboratories applied PCR; two also applied ELISA techniques. Sensitivity and specificity were determined for each laboratory and concordance of results among the laboratories was evaluated by Cohen Kappa coefficient. RESULTS: Poor concordance (3 of 10 paired comparisons had values of Kappa > 0.4), low sensitivity and specificity across all laboratories, and poor performance of both techniques in detecting E. granulosus in canine feces was demonstrated in this study. An ex-post comparison of the laboratories' test protocols showed substantial heterogeneity that could partially explain poor concordance of results. CONCLUSION: The results underscore the heterogeneity of canine echinococcosis diagnosis across the region and indicate possible sources of variability. Efforts to standardize canine echinococcosis testing must be included in the plan of action for the Regional Initiative for the Control of Cystic Echinococcosis. Future comparisons with fecal samples of known parasite load are needed.

Proximate determinants of tuberculosis in Indigenous peoples worldwide: a systematic review.

BACKGROUND: Indigenous peoples worldwide carry a disproportionate tuberculosis burden. There is an increasing awareness of the effect of social determinants and proximate determinants such as alcohol use, overcrowding, type 1 and type 2 diabetes, substance misuse, HIV, food insecurity and malnutrition, and smoking on the burden of tuberculosis. We aimed to understand the potential contribution of such determinants to tuberculosis in Indigenous peoples and to document steps taken to address them. METHODS: We did a systematic review using seven databases (MEDLINE, Embase, CINAHL, Global Health, BIOSIS Previews, Web of Science, and the Cochrane Library). We identified English language articles published from Jan 1, 1980, to Dec 20, 2017, reporting the prevalence of proximate determinants of tuberculosis and preventive programmes targeting these determinants in Indigenous communities worldwide. We included any randomised controlled trials, controlled studies, cohort studies, cross-sectional studies, case reports, and qualitative research. Exclusion criteria were articles in languages other than English, full text not available, population was not Indigenous, focused exclusively on children or older people, and studies that focused on pharmacological interventions. FINDINGS: Of 34 255 articles identified, 475 were eligible for inclusion. Most studies confirmed a higher prevalence of proximate determinants in Indigenous communities than in the general population. Diabetes was more frequent in Indigenous communities within high-income countries versus in low-income countries. The prevalence of alcohol use was generally similar to that among non-Indigenous groups, although patterns of drinking often differed. Smoking prevalence and smokeless tobacco consumption were commonly higher in Indigenous groups than in non-Indigenous groups. Food insecurity was highly prevalent in most Indigenous communities evaluated. Substance use was more frequent in Indigenous inhabitants of high-income countries than of low-income countries, with wide variation across Indigenous communities. The literature pertaining to HIV, crowding, and housing conditions among Indigenous peoples was too scant to draw firm conclusions. Preventive programmes that are culturally appropriate targeting these determinants appear feasible, although their effectiveness is largely unproven. INTERPRETATION: Indigenous peoples were generally reported to have a higher prevalence of several proximate determinants of tuberculosis than non-Indigenous peoples, with wide variation across Indigenous communities. These findings emphasise the need for community-led, culturally appropriate strategies to address smoking, food insecurity, and diabetes in Indigenous populations as important public health goals in their own right, and also to reduce the burden of tuberculosis. FUNDING: Canadian Institutes of Health Research.

Combination of surveillance tools reveals that Yellow Fever virus can remain in the same Atlantic Forest area at least for three transmission seasons

BACKGROUND In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.

Talar Body Reconstruction for Nonunions and Malunions.

BACKGROUND: Talar body and neck nonunions and malunions may undergo a reconstructive surgery when joint cartilage is still viable, and no talar collapse or infection has occurred. This is a rare condition and the studies supporting the procedure have small number of cases. The objective of the present study is to report a case series of six patients who underwent talar reconstructions. MATERIALS AND METHODS: Six patients with talar malunions or nonunions who underwent surgical treatment were reviewed in this retrospective study. There were three nonunions and two malunions of the talar body and one malunion of the talar neck. Clinical evaluation included all the parameters used in the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scale. Arthritic degeneration of the ankle joint was assessed according to a modified Bargon scale. RESULTS: The mean followup was 86 months (range 24-282 months). There were no cases of postoperative avascular necrosis of the talus. Four of the six patients in our series required a subtalar fusion as part of the reconstruction procedure. The average preoperative AOFAS hindfoot score was 34, and at the time of the last evaluation, it was 74. The mean preoperative score on the modified Bargon scale for the tibiotalar joint was 1.17. At the last followup, it rose to 1.33. Three different deformities of the talus were identified (a) flattening of the talus (b) extra-articular step and (c) intraarticular step. CONCLUSION: Reconstruction of talar nonunions and malunions improved function in selected patients with a low risk of complications. Three different anatomical patterns of talar nonunions and malunions were identified.

Effective charges and zeta potentials of oil in water microemulsions in the presence of Hofmeister salts.

We present a theory which allows us to calculate the effective charge and zeta potential of oil droplets in microemulsions containing Hofmeister salts. A modified Poisson-Boltzmann equation is used to account for the surface and ion polarizations and hydrophobic and dispersion interactions. The ions are classified as kosmotropes and chaotropes according to their Jones-Dole viscosity B coefficient. Kosmotropes stay hydrated and do not enter into the oil phase, while chaotropes can adsorb to the oil-water interface. The effective interaction potentials between ions and oil-water interface are parametrized so as to accurately account for the excess interfacial tension.

Representações de puérperas sobre o cuidado recebido no trabalho de parto e parto / The representations puerperal women have about the care they received during labor

Resumo Objetivo: descrever as representações sociais de puérperas sobre o cuidado recebido durante o trabalho de parto e parto. Metodologia: trata-se de um estudo descritivo baseado na Teoria do Núcleo Central, desenvolvido com 119 puérperas em uma maternidade pública localizada no Brasil, na cidade de Fortaleza, Ceará. Os dados foram coletados por meio do Teste de Associação Livre de Palavras, que continha como estímulos indutores: trabalho de parto, parto, cuidado no trabalho de parto e parto, sendo transcritos e analisados pelo software Evoc. Resultados: a partir da análise estrutural, os vocábulos dor, felicidade e orientação apresentaram maior frequência como elemento central dos respectivos termos indutores. Conclusão: por meio dos resultados obtidos, é possível afirmar que o momento do trabalho de parto e do parto é crucial para que o enfermeiro planeje e execute uma adequada assistência durante o processo de parturição a fim de reduzir o impacto das representações negativas em relação a esse processo.

Resumen Objetivo: describir las representaciones sociales de puérperas sobre el cuidado recibido durante el trabajo de parto y parto. Metodología: se trata de un estudio descriptivo basado en la Teoría del Núcleo Central, desarrollado con 119 madres, en un hospital público de Fortaleza, Ceará, Brasil. Los datos fueron recolectados por medio del Test de Asociación de Palabras, que contenía como estímulos inductores: cuidado, trabajo de parto, parto, cuidado en el trabajo de parto y en el parto, siendo transcritos y analizados por el software Evoc. Resultados: a partir del análisis estructural, los vocablos dolor, felicidad y orientación presentaron mayor frecuencia como elemento central de los respectivos términos inductores. Conclusión: por medio de los resultados obtenidos, es posible afirmar que el momento del trabajo de parto y el parto es crucial para que el enfermero planee y ejecute una adecuada asistencia durante el proceso de parto con el fin de reducir el impacto de las representaciones negativas en relación con ese proceso.

Abstract Objective: to describe the social representations puerperal women have about the care they received during labor and delivery. Methodology: this is a descriptive study, based on the Theory of the Central Nucleus, which was undertaken with 119 women in the postpar-tum period in a public maternity hospital, located in the city of Fortaleza, Ceará, Brazil. The data were collected through the Free Word Association Test, which included as inductive stimuli: care, labor, delivery and care in labor and delivery. The data were transcribed and analyzed with Evoc software. Results: the structural analysis showed that the words "pain", "happiness" and "guidance" ocurred more frequency as a central feature of the respective inducing terms. Conclusion: the results confirm that the moment of labor and delivery is crucial for nurses in the planning and implementation of adequate care during parturition insofar, as such measures lessen the impact of negative representations of childbirth.

Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3 Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in Folate-Targeted Liposomes.

Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.

Minimally invasive posteromedial percutaneous plate osteosynthesis for diaphyseal tibial fractures: technique description.

PURPOSE: The aim of this study was to evaluate the feasibility of performing minimally-invasive plate osteosynthesis (MIPO) in tibial fractures using two posteromedial incisions, and to measure the distance between the plate and neurovascular structures. MATERIALS AND METHODS: We performed nine dissections of specimens that were submitted to tibial MIPO with two posteromedial incisions. One locking compression plate (LCP) of 14 to 16 holes was inserted into the submuscular tunnel in a retrograde manner. Incisions were linked to evaluate the distance between neurovascular structures and the plate. RESULTS: During the proximal incision, a blunt dissection between semitendinosus and medial gastrocnemius tendons, as well as their lateral shift, helped to protect the main local neurovascular structures. In its distal portion, the submuscular plate tunnel insertion and its direction to the proximal incision prevented direct contact and possible damage to neurovascular structures. Moreover, we obtained successful results from a patient submitted to this procedure. CONCLUSION: Posteromedial MIPO represents a safe and attractive alternative for tibial fractures, particularly if there are damaged soft tissues in the anterior and medial side, or when access to intramedullary osteosynthesis is blocked.

Cadaveric assessment of a 3D-printed aiming device for implantation of a hinged elbow external fixator.

INTRODUCTION: Proper implantation of a hinged external elbow fixator (HEEF) is demanding since it requires precise alignment between the flexion-extension's and HEEF's axis. In order to optimize this alignment, we have developed a 3D-printed aiming device. The primary goal of the study was to compare the aiming device-based technique with the conventional pin technique. The secondary goal was to determine whether it is possible to share the aiming device with the surgical community. MATERIALS AND METHODS: A HEEF was implanted in cadavers with either the aiming device (n = 6) or the conventional pin technique (n = 6). For both techniques the duration of the procedure, the radiation exposure as well as the offset and angular divergence between the HEEF's and flexion-extension's axis were compared. To achieve the secondary goal, two surgeons used aiming devices 3D-printed from files sent by email in order to implant HEEF on cadaveric specimens (n = 6). RESULTS: Duration of the procedure was not significantly different between both techniques. However, the aiming device allowed for reduction of the number of image intensifier shots (p = 0.005), angular divergence (p = 0.02) and offset between both axes (p = 0.05). The aiming devices have been delivered less than 15 days after ordering, and they have allowed proper implantation of six HEEF. CONCLUSION: The 3D-printed aiming device allowed less irradiant and more accurate implantation of HEEF. It is possible to share it with other surgeons.

Qualidade de vida no trabalho dos profissionais da saúde de uma Unidade Básica de Saúde / Calidad de vida en el trabajo de los profesionales de salud de una Unidad Básica de salud / Quality of life in the work of health professionals from a basic health unit

Introdução: a qualidade de vida no trabalho é um componente global da vida do trabalhador e essencial para a satisfação no trabalho e na vida. Objetivo: avaliar a qualidade de vida dos profissionais de saúde da Unidade Básica de Saúde Delson Pinheiro de Aguiar em Serranópolis de Minas. Métodos: trata-se de uma pesquisa descritiva, transversal e quantitativa realizada com 12 profissionais de saúde, no período de março a abril de 2015 através de uma entrevista adaptada segundo o modelo de satisfação de Walton (1973). Resultados: constatou-se a predominância do sexo feminino (66,7 por cento), a idade variou entre 20 e 50 anos, os casados eram maioria (75 por cento), assim como os profissionais de ensino superior completo (58,4 por cento), a renda variou de um salário mínimo até três ou mais. A média global de satisfação foi de 2,83 (±0,81), o que indica que estes profissionais se encontram insatisfeitos e um pouco insatisfeitos. Conclusões: os profissionais carecem de melhores condições de trabalho, oportunidades de crescimento dentro da instituição e segurança em relação à manutenção do emprego, de forma a contribuir positivamente para melhorar a imagem da instituição e participação da comunidade e na qualidade dos serviços prestados(AU)

Introducción: la calidad de vida en el trabajo es un componente global de la vida del trabajador y esencial para la satisfacción en el trabajo y la vida. Objetivo: evaluar la calidad de vida de los profesionales sanitarios de la Unidad Básica de Salud Delson Pinheiro de Aguiar en Serranópolis de Minas. Métodos: estudio descriptivo, transversal y encuesta cuantitativa con 12 profesionales de la salud, en período a partir de marzo y abril de 2015 a través de una entrevista adaptada según el modelo de la satisfacción Walton (1973). Resultados: se encontró un predominio del sexo femenino (66,7 por ciento), con edades comprendidas entre 20 y 50 años, eran mayoría casados (75 por ciento), así como los profesionales de la educación superior completos (58,4 por ciento), ingreso osciló entre un mínimo de hasta el salario de tres o más. La satisfacción media global fue de 2,83 (± 0,81), lo que indica que estos profesionales no están satisfechos y algo insatisfecho. Conclusión: los profesionales necesitan mejores condiciones de trabajo, oportunidades de crecimiento dentro de la institución y de seguridad para el mantenimiento del empleo a fin de contribuir positivamente a mejorar la imagen de la institución y la comunidad la participación y la calidad de los servicios prestados(AU)

Introduction: Quality of life in the work is a global component of the worker's life and essential for the satisfaction with work and life. Objective: Assess the quality of life of health professional from Delson Pinheiro de Aguiar Basic Health Unit in Serranopolis, Minas. Methods: Descriptive, cross-sectional study and quantitative survey with 12 health professionals, in the period from March to April 2015, by means of an interview adapted to Watson's satisfaction model (1973). Results: We found a predominance of the female sex (66.7 percent), at ages buttes 20 and 50 years, most of them were married (75 percent), as well as complete higher education professionals (58.4 percent), incomes ranged between a minimum of up to the salary of three or more. Global mean satisfaction was 2.83 (± 0.81), a value indicating that these professionals are not satisfied but quite dissatisfied. Conclusion: The professionals need better working conditions, opportunities for growing within the institutions, and secureness for maintaining their employments, in order to positively contribute to improve the institution's and community's image, as well as the quality of the services(AU)

Single-Nucleotide Resolution Mapping of Hepatitis B Virus Promoters in Infected Human Livers and Hepatocellular Carcinoma.

Hepatitis B virus (HBV) is a major cause of liver diseases, including hepatocellular carcinoma (HCC), and more than 650,000 people die annually due to HBV-associated liver failure. Extensive studies of individual promoters have revealed that heterogeneous RNA 5' ends contribute to the complexity of HBV transcriptome and proteome. Here, we provide a comprehensive map of HBV transcription start sites (TSSs) in human liver, HCC, and blood, as well as several experimental replication systems, at a single-nucleotide resolution. Using CAGE (cap analysis of gene expression) analysis of 16 HCC/nontumor liver pairs, we identify 17 robust TSSs, including a novel promoter for the X gene located in the middle of the gene body, which potentially produces a shorter X protein translated from the conserved second start codon, and two minor antisense transcripts that might represent viral noncoding RNAs. Interestingly, transcription profiles were similar in HCC and nontumor livers, although quantitative analysis revealed highly variable patterns of TSS usage among clinical samples, reflecting precise regulation of HBV transcription initiation at each promoter. Unlike the variety of TSSs found in liver and HCC, the vast majority of transcripts detected in HBV-positive blood samples are pregenomic RNA, most likely generated and released from liver. Our quantitative TSS mapping using the CAGE technology will allow better understanding of HBV transcriptional responses in further studies aimed at eradicating HBV in chronic carriers. IMPORTANCE: Despite the availability of a safe and effective vaccine, HBV infection remains a global health problem, and current antiviral protocols are not able to eliminate the virus in chronic carriers. Previous studies of the regulation of HBV transcription have described four major promoters and two enhancers, but little is known about their activity in human livers and HCC. We deeply sequenced the HBV RNA 5' ends in clinical human samples and experimental models by using a new, sensitive and quantitative method termed cap analysis of gene expression (CAGE). Our data provide the first comprehensive map of global TSS distribution over the entire HBV genome in the human liver, validating already known promoters and identifying novel locations. Better knowledge of HBV transcriptional activity in the clinical setting has critical implications in the evaluation of therapeutic approaches that target HBV replication.