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Introduction: Women continue to be underrepresented in the majority of surgical specialties, including neurosurgery. Research question: In this multinational survey, we aimed to assess current gender disparities in neurosurgery focusing on job satisfaction and inequity/discrimination at work. Material and methods: Female and male members of the European Association of Neurosurgical Societies were asked to complete an electronic survey (Google Forms, Mountain View) containing demographic baseline data and questions on attitudes regarding gender disparity, personal experience with gender inequity and career satisfaction/work-life balance. Quantitative analyses were performed to analyse the responses, including summary and comparative statistics. Results: We received 168 responses from 40 different countries. Survey responders had a mean age of 40.8 ​± ​11.5 years; 29.8% were female. There were significant more male than female residents and attending surgeons per department. Eighty-eight percent of female and 38.1% of male responders experienced gender inequity or discrimination at work (adjusted OR 10.8, 95%CI 4.2–27.8, p

OBJETIVO: Identificar o perfil lipídico e a peroxidação de lipídeos no plasma de crianças e adolescentes com sobrepeso e obesidade atendidos no Ambulatório de Endocrinologia Pediátrica do HOSPED/UFRN. MÉTODOS: Foram constituídos grupos com crianças e adolescentes com sobrepeso (n = 15), obesidade (n = 30) e controle (n = 21). O perfil lipídico foi avaliado por meio do colesterol total, LDL-colesterol, HDL-colesterol e triglicerídeos. A peroxidação de lipídeos no plasma foi medida pelo marcador malonildialdeído (MDA). A análise estatística foi realizada através do teste t de Student, teste de Tukey, ANOVA e correlação de Pearson. RESULTADOS: As alterações de colesterol total e LDL-colesterol estavam mais presentes nos grupos sobrepeso e obesidade masculinos. O HDL-colesterol mostrou-se em condições limítrofes nos grupos sobrepeso e obesidade em ambos sexos. As maiores concentrações de triglicerídeos foram registradas no grupo obesidade feminino. Identificou-se elevada peroxidação de lipídeos no plasma no grupo obesidade, principalmente no sexo masculino. CONCLUSÕES: Na amostra estudada, maiores alterações do perfil lipídico foram observadas no sexo masculino nos grupos sobrepeso e obesidade, e a peroxidação de lipídeos estava mais evidente no grupo obesidade em ambos sexos.

Background & Aims: Renal dysfunction is prevalent in advanced chronic liver disease (aCLD) and is associated to liver-related death (LRD). This makes a reliable evaluation of renal function (RF) a crucial aspect. RF can be estimated by formulas or measured by gold standard method. Estimated RF is not reliable in aCLD. However, there is a lack of information on the reliability of formulas in the prediction of LRD., Methods: We analysed a cohort of patients with aCLD in whom RF was measured by the plasma clearance of iohexol (mGFR) and estimated (eGFR) by formulas: MDRD, CKD-EPI, Royal Free Hospital (RFHC), GRAIL and Mindikoglu-eGFR. LRD was defined as death from hepatic causes. Multivariable analysis was used to evaluate association of mGFR or eGFR with LRD., Results: 161 patients were evaluated, with median follow-up of 28 months, 58 died from LRD. In overall group mGFR (OR 0.99; p = 0.022) and formulas: CKD-EPI (OR 0.98; p = 0.044), GRAIL (OR 0.98; p = 0.038) was associated with LRD. In patients with normal creatinine levels (≤ 1.1 mg/dL), mGFR (OR 0.99; p = 0.031) was whereas any formula was not associated with LRD., Conclusions: eGFR appears as an unreliable method for predicting LRDs in aCLD, especially in those with lower creatinine levels. By contrast, mGFR seems to be a superior predictor., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest for the reported study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We evaluated the available literature on the association between characteristics of the food environment and household food insecurity., Study Design: Systematic review., Methods: Studies published until January 9th, 2023, were searched in the PubMed, Web of Science, Science Direct, EMBASE and LILACS databases. The included studies were summarized with a narrative synthesis with information on the study location, population studied, prevalence and type of measure/instrument used to assess food (in)security, method of evaluating the food environment and measure between food insecurity and food environment., Results: Twenty-two articles were included. Different methods were used to measure food security and the food environment. Most food insecurity assessment tools assessed the dimension of access to food, more precisely economic access. The dimensions of the food environment most evaluated were food availability and affordability. An association between characteristics of the food environment and food insecurity was found in 18 of these studies. Homes with food insecurity have a greater availability of unhealthy foods, more frequent purchasing of foods in convenience stores and small markets as well as a lower availability of healthy foods, such as fruits and vegetables., Conclusions: This review revealed that household food insecurity was associated with the food environment, highlighting the importance of policies to promote healthy diets, especially in vulnerable communities. Few studies were found in the Global South, demonstrating the gap in this knowledge in these locations., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Lungworm infection, or verminous pneumonia, is a parasitic disease that causes serious problems in small and large ruminants. Despite the fact that nematodes of the genus Dictyocaulus in cattle and sheep are the main cause of this disease, there are few studies on the natural infections of South American camelids. For this reason, this study aims to report the natural infection by Dictyocaulus filaria in vicunas (Vicugna vicugna) for the first time. During a shearing season (chaku) in Cuzco, Peru, two accidentally killed adult vicunas were submitted to the IVITA-Marangani research center in Cuzco for their respective necropsies. The tracheas of both vicunas had numerous nematodes, as seen during the necropsy. The nematodes were collected in 70% ethanol and were morphologically identified as D. filaria. Likewise, the DNA of six nematodes was extracted, and the ITS2 region and the 28S rRNA gene were amplified and sequenced. The nucleotide sequences of both genetic markers were up to 100% identical with previously reported D. filaria DNA sequences found in the goat yearlings from Turkey, sheep from Iran, Turkey, and India, and the argali from Uzbekistan, which confirmed the morphological diagnosis. This finding represents the first molecular confirmation of a natural D. filaria infection in a South American camelid. It will be necessary to carry out future studies to know the current situation of verminous pneumonia in domestic and wild South American camelids and to know the negative effects of the disease on them., Competing Interests: Declaration of competing interest Not applicable., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Toxoplasmosis is a foodborne disease caused by the protozoan Toxoplasma gondii, and transmitted to humans by eating raw or undercooked meat, mainly. Poultry, beef, and pork are the main meats consumed in Peru; despite this, guinea pig meat is also widely consumed. For this reason, the objective of this study was to molecularly detect T. gondii in domestic and wild guinea pigs from the Marangani district in Cuzco, Peru, and identify some risk factors associated with this pathogen. DNA was extracted from the brain tissue samples of guinea pigs (30 domestic and 30 wild), and PCR protocols were used to amplify the internal transcribed spacer (ITS-1) region and a 529 bp fragment from the T. gondii genome. T. gondii DNA was detected in 14 (23.3%) guinea pigs. T. gondii frequency was 33.3% in domestic guinea pigs and 13.3% in wild guinea pigs. Our results demonstrated that guinea pigs represent an important source for T. gondii infection in human populations in this locality., Competing Interests: Declaration of competing interest Not applicable., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To analyze the presence of protozoan parasites in bird coprolites from the Tremembé Formation (Oligocene of the Taubaté Basin)., Materials: Twenty avian coprolites embedded in pyrobituminous shale matrices., Methods: Samples were rehydrated and subjected to spontaneous sedimentation., Results: Paleoparasitological analyses revealed oocysts compatible with the Eimeriidae family (Apicomplexa) and one single Archamoebae (Amoebozoa) cyst., Conclusions: The present work increases the amount of information about the spread of infections throughout the Cenozoic Era and reveals that the Brazilian paleoavifauna played an important role in the Apicomplexa and Amoebozoa life cycles., Significance: This is the first record of protozoans in avian coprolites from the Oligocene of Brazil. These findings can help in the interpretation of phylogenies of coccidian parasites of modern birds, as certain taxonomic characters observed in the Oligocene Protozoa characterize monophyletic groups in current molecular phylogenetic analyses., Limitations: None of the oocysts were sporulated; therefore, it is not possible to identify the morphotypes to genus or species., Suggestions for Further Research: Our results create new perspectives related to biogeographic studies of the parasitic groups described and may improve the understanding of the temporal amplitude of parasitic evolutionary relationships between Protozoans and birds., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine the effects of in-utero exposure to maternal SARS-CoV-2 infection on offspring's neurodevelopment during the first year of life., Methods: We performed a prospective cohort of babies exposed to SARS-CoV-2 during pregnancy, and a control group (CG) of unexposed babies in a low-income area in Brazil. Children's neurodevelopment was assessed using the guide for Monitoring Child Development in the Integrated Management of Childhood Illness context for both groups (at 1,2,3,4,5,6, 9, and 12 months), and the Ages & Stages Questionnaire (ASQ-3) for the exposed group (EG) (at 4, 6 and 12 months)., Results: We followed 137 children for 1 year, 69 in the COVID-19-EG, and 68 in the CG. All mothers were unvaccinated at the time of cohort inclusion, and maternal demographics were similar in the two groups. 20.3% of EG children and 5.9% of the CG received a diagnosis of neurodevelopmental delay within 12 months of life (P = 0.013, relative risk = 3.44; 95% confidence interval, 1.19- 9.95). For the EG, the prevalence of neurodevelopment impairment using Ages & Stages Questionnaire was 35.7% at 4 months, 7% at 6 months, and 32.1% at 12 months., Conclusion: SARS-CoV-2 exposure was associated with neurodevelopmental impairment, and specific guidelines are needed for the follow-up of these high-risk children to mitigate the long-term effects on children's health., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Accidents involving spiders from the genus Loxosceles cause medical emergencies in several countries of South America. The species Loxosceles laeta is ubiquitously present in Peru and is responsible for severe accidents in this country. To further characterize L. laeta venom components and to unveil possible variations in the Peruvian population, we provide an overview of the toxins-related transcripts present in the venom gland of Peruvian L. laeta. A dataset from a cDNA library previously sequenced by MiSeq sequencer (Illumina) was re-analyzed and the obtained data was compared with available sequences from Loxosceles toxins. Phospholipase-D represent the majority (69,28 %) of the transcripts related to venom toxins, followed by metalloproteases (20,72 %), sicaritoxins (6,03 %), serine-proteases (2,28 %), hyaluronidases (1,80 %) and Translationally Controlled Tumor Protein (TCTP) (0,56 %). New sequences of phospholipases D,sicaritoxins, hyaluronidase, TCTP and serine proteinases were described. Differences between the here-described toxin sequences and others, previously identified in venom glands from other spiders, were visualized upon sequence alignments. In addition, an in vitro hyaluronidase activity assay was also performed to complement comparisons between Peruvian and Brazilian L. laeta venom enzymatic activities, revealing a superior activity in the venom from Brazilian specimens. These new data provide a molecular basis that can help to explain the difference in toxicity among L. laeta venoms from different countries in South America., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Herein we report the synthesis of five new mononuclear mixed ligand oxidovanadium(IV) complexes [V IV O(L 1-3 )(L NN )] (1-5) with tridentate O,N,O-donor aroylhydrazones as main ligand (H 2 L 1-3 ) and N,N-chelating 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) as co-ligand (L NN ). The complexes were characterized by elemental and thermogravimetric analysis (TGA), IR, UV-vis, and electron paramagnetic resonance (EPR) spectroscopy, electrospray ionization-mass spectrometry (ESI-MS) and cyclic voltammetry (CV). The structure of 1-5 was confirmed by single crystal X-ray analysis and also optimized by density functional theory (DFT) methods. At physiological pH an equilibrium [V IV O(L 1-3 )(L NN )] + H 2 O ⇄ [V IV O(L 1-3 )(H 2 O)] + L NN , shifted towards left, is established, with water molecule that could be replaced by the biomolecules of the organism. The studies on the interaction with two proteins, lysozyme (Lyz) chosen as a representative model of a small protein, and human serum albumin (HSA) show that two types of binding are possible: a non-covalent binding through the accessible residues on protein surface with [V IV O(L 1-3 )(L NN )] keeping its octahedral structure, and a covalent binding upon the replacement of water in [V IV O(L 1-3 )(H 2 O)] with His-N donors to form V IV O(L 1-3 )(HSA). In vitro cytotoxicity of ligands and complexes were screened against human cervical cancer (HeLa) (IC 50  = 7.39-15.13 μM), colon cancer (HT-29) (IC 50  = 11.04-28.20 μM) and mouse embryonic fibroblast (NIH-3T3) cell lines (IC 50  = 62.22-87.75 μM) by MTT assay. Particularly, 5 showed higher cytotoxicity than cisplatin and cyclophosphamide, with an IC 50 of 7.39 ± 1.21 μM and 11.04 ± 0.29 μM against HeLa and HT-29., (Copyright © 2022. Published by Elsevier Inc.)

In this work, one oxidomethoxidovanadium(V) [V V O(L)(OMe)] (1) and two mixed-ligand oxidovanadium(IV) [V IV O(L)(phen)] (2), and [V IV O(L)(bipy)] (3) complexes have been synthesized using a tridentate bi-negative ONS donor dithiocarbazate as main ligand, H 2 L [where, H 2 L = S-benzyl-3-(2-hydroxy-3-ethoxyphenyl)methylenedithiocarbazate] along with 1,10-phenanthroline (phen) (for 2) and 2,2'-bipyridine (bipy) (for 3) as co-ligands. The ligand and complexes have been characterised by FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Distorted square pyramidal for 1, and distorted octahedral geometry for 2 and 3 was confirmed by single crystal X-ray crystallography. The behavior of 1-3 in solution medium has been investigated through various physicochemical techniques. It is observed that 1 completely and 2-3 partially decomposes and converts into a penta-coordinated species, [V IV O(L)(DMSO/H 2 O)] after the release of the methoxido group (1) or breaking of the diimine based co-ligands (2 and 3) in DMSO/aqueous solution. Interestingly, in DMSO/aqueous solution, 1 gets completely reduced and converted into the corresponding oxidovanadium(IV) species. Interaction of 1-3 with calf thymus DNA (CT-DNA) was investigated and the results show, complex 2 exhibited the maximum binding constants, K b  = 7.12 × 10 4  M -1 . The anticancer potential of 1-3 was evaluated by cell viability assay against human breast carcinoma cell, MCF-7, and noncancerous mouse embryonic cell, NIH-3T3 and 2 was found to be the most cytotoxic complex (IC 50  = 6.73 ± 0.36 μM) in the series. In addition, 2 selectively inhibit colony formation compared to the rest complexes. Also, the cell cycle studies of the complexes were performed using flow cytometry analysis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Two new μ 2 -oxido bridged divanadium (V) complexes, [V V 2 O 3 (L 1,2 ) 2 ] (1 and 2) have been synthesized using bi-negative tridentate ONO-donor ligands, H 2 L 1,2 (H 2 L 1  = 4-tert-butyl-2-[[[3,5-di-tert-butyl-2-hydroxyphenyl]methylene]amino]phenol and H 2 L 2  = 5-bromo-2-[[[4-(diethylamino)-2-hydroxyphenyl]methylene]amino]phenol). The synthesized ligands and complexes have been characterized through FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Single crystal X-ray crystallography data confirmed distorted square pyramidal geometry for both the complexes. The aqueous phase stability of these complexes has been evaluated through HR-ESI-MS in CH 3 CN:H 2 O (80:20) mixture. Thereafter their interaction with calf thymus DNA (CT-DNA) have been studied using electronic absorption and fluorescence spectroscopy, revealing an intercalation mode of binding, with binding constant in the order of 10 4  M -1 . Moreover, bovine serum albumin (BSA) interaction of 1 and 2 has been evaluated via fluorescence quenching experiment, which suggests that the quenching mechanism is static (~10 13  M -1  = 13.57-16.62 μM) and normal mouse embryonic fibroblasts cells (NIH-3T3). The mechanism of cell death brought about by these complexes was studied by nuclear staining, cell cycle and Annexin V/PI double staining apoptotic assay. These studies indicate that 1 and 2 exert inhibitory effects on the S and G2M phase of cell cycle, which is an indication of apoptotic cell death. Also, a clonogenic assay was performed, which showed that the complexes could effectively inhibit colony formation.50  = 13.57-16.62 μM) and normal mouse embryonic fibroblasts cells (NIH-3T3). The mechanism of cell death brought about by these complexes was studied by nuclear staining, cell cycle and Annexin V/PI double staining apoptotic assay. These studies indicate that 1 and 2 exert inhibitory effects on the S and G2M phase of cell cycle, which is an indication of apoptotic cell death. Also, a clonogenic assay was performed, which showed that the complexes could effectively inhibit colony formation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Metal homeostasis is fundamental for optimal performance of cell metabolic pathways. Over the course of evolution, several systems emerged to warrant an intracellular metal equilibrium. When exposed to growth-challenging copper concentrations, Gram-negative bacteria quickly activate copper-detoxification mechanisms, dependent on transmembrane-protein complexes and metallochaperones that mediate metal efflux. Here, we show that vesiculation is also a common bacterial response mechanism to high copper concentrations, and that extracellular vesicles (EVs) play a role in transporting copper. We present evidence that bacteria from different ecological niches release copious amounts of EVs when exposed to copper. Along with the activation of the classical detoxification systems, we demonstrate that copper-stressed cells of the cyanobacterium Synechocystis sp. PCC6803 release EVs loaded with the copper-binding metallochaperone CopM. Under standard growth conditions, CopM-loaded EVs could also be isolated from a Synechocystis strain lacking a functional TolC-protein, which we characterize here as exhibiting a copper-sensitive phenotype. Analyses of Synechocystis tolC-mutant's EVs isolated from cells cultivated under standard conditions indicated the presence of copper therein, in significantly higher levels as compared to those from the wild-type. Altogether, these results suggest that release of EVs in bacteria represent a novel copper-secretion mechanism, shedding light into alternative mechanisms of bacterial metal resistance., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lung cancer is a major cause of death among people experiencing homelessness, with mortality rates more than double those in the general population. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) could reduce lung cancer deaths in this population, although the circumstances of homelessness present multiple barriers to LCS LDCT completion. Patient navigation is a promising strategy for overcoming these barriers., Methods: The Investigating Navigation to Help Advance Lung Equity (INHALE) Study is a pragmatic randomized controlled trial of patient navigation for LCS among individuals receiving primary care at Boston Health Care for the Homeless Program (BHCHP). Three hundred BHCHP patients who meet Medicare/Medicaid criteria for LCS will be randomized 2:1 to usual care with (n = 200) or without (n = 100) LCS navigation. Following a structured, theory-based protocol, the patient navigator assists with each step in the LCS process, providing lung cancer education, facilitating shared decision-making visits with primary care providers (PCPs), assisting in making and attending LCS LDCT appointments, arranging follow-up when needed, and offering tobacco cessation support for smokers. The primary outcome is receipt of LCS LDCT at 6 months. Using a sequential explanatory mixed methods approach, qualitative interviews with participants and PCPs will aid in interpreting and contextualizing the trial results., Discussion: This trial will produce the first experimental evidence on patient navigation for cancer screening in a homeless health care setting. Results could inform cancer health equity efforts at the 299 Health Care for the Homeless programs that serve over 900,000 patients annually in the US., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Envenomation due to a Loxosceles spider bite is a rare event in France and no case concerning the breast has yet been reported. We report the case of a 48-year-old woman who presented at Saint-Etienne University Hospital with a pulsatile pain in her left breast two days after feeling a fleeting bite. An abscess was diagnosed and antibiotics were prescribed. A few days later, a necrotic zone appeared around the areola and 75 percent of the surrounding skin was inflamed. The patient reported a persistent fever and a burning pain in her breast. Loxoscelism was finally concluded and surgical debridement was undertaken, followed by supervised wound therapy and local skin care. Complete healing was achieved after 4 weeks of treatment. The diagnosis of loxoscelism is generally presumptive, as the bite is usually painless and the spider rarely captured. Its diagnosis should be considered when an abscess responds poorly to antibiotics., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Apical hypertrophic cardiomyopathy (AHCM) is a rare cardiomyopathy, in which hypertrophy occurs predominantly in the ventricular apex, and in some cases with a high risk of sudden cardiac death., Objective: The aim of this paper is to present a case series of patients with AHCM and describe their main clinical, echocardiographic and electrocardiographic characteristics, the recommendation for an implantable cardioverter-defibrillator (ICD) and the frequency of sudden cardiac death (SCD)., Methods: A retrospective case series was conducted at the referral center of a federal teaching hospital, between the years 2005 to 2020, involving patients with an echocardiographic diagnosis of AHCM. The parameters of the American College of Cardiology and the European Society of Cardiology were used to assess the risk of SCD., Results: A total of 11 individuals were assessed with a mean age of 55.3 years, mean follow-up of 41.2 months, most of whom were symptomatic at diagnosis (72.7%). The most frequent symptom was dyspnea (27.3%). A family history of SCD was described in 45.5% of cases. Due to a high risk of SCD, four patients received ICDs. One patient presented sudden cardiac death after having refused the ICD., Conclusions: Symptoms and alterations in the imaging exams are significant factors in the clinical and prognostic assessment of patients with AHCM., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: While substantial attention is focused on the delivery of routine preventive cancer screening, less attention has been paid to systematically ensuring that there is timely follow-up of abnormal screening test results. Barriers to completion of timely follow-up occur at the patient, provider, care team and system levels., Methods: In this pragmatic cluster randomized controlled trial, primary care sites in three networks are randomized to one of four arms: (1) standard care, (2) "visit-based" reminders that appear in a patient's electronic health record (EHR) when it is accessed by either patient or providers (3) visit based reminders with population health outreach, and (4) visit based reminders, population health outreach, and patient navigation with systematic screening and referral to address social barriers to care. Eligible patients in participating practices are those overdue for follow-up of an abnormal results on breast, cervical, colorectal and lung cancer screening tests., Results: The primary outcome is whether an individual receives follow-up, specific to the organ type and screening abnormality, within 120 days of becoming eligible for the trial. Secondary outcomes assess the effect of intervention components on the patient and provider experience of obtaining follow-up care and the delivery of the intervention components., Conclusions: This trial will provide evidence for the role of a multilevel intervention on improving the follow-up of abnormal cancer screening test results. We will also specifically assess the relative impact of the components of the intervention, compared to standard care., Trial Registration: ClinicalTrials.gov NCT03979495., (Copyright © 2021. Published by Elsevier Inc.)

This article aims to assess the loss of financial well-being in the COVID-19 pandemic. The developed theoretical model identifies the impacts of the perception of financial risk and financial anxiety on financial well-being. It also seeks, through a comparative analysis, to assess whether public servants, due to their status of job stability in Brazil, are less likely to have the effects of the pandemic than private employees. A survey was carried out on 1222 Brazilians with structural equation modeling and multi-group invariance tests. The results indicate that lower financial well-being is influenced by the level of financial anxiety and financial risk. Public servants perceive fewer losses in financial well-being, anxiety and risks than other professions. In the pandemic context, where the risks of unemployment and loss of income are increased, job stability works like an insurance, allowing public servants greater financial security and then minor losses of financial well-being. Evidence indicates that in countries where a large percentage of workers have temporary or informal jobs, the challenge of reducing the financial impacts of the pandemic will be great. Interventions to alleviating anxiety and public policies of income transfer and reduction of unemployment are instruments to reduce the loss of financial well-being., (© 2021 Elsevier B.V. All rights reserved.)

Given that oral preparations of benznidazole (BZN) have demonstrated limited efficacy in the treatment of Chagas' disease due to pharmacokinetic or toxicological problems, the development of buccal polymeric films was purposed in this study. These systems ensure high patient acceptability and direct access to the systemic circulation, improving drug bioavailability and toxicological profile. Polymer films were prepared through a thermopressing method by mixing BZN and polyvinyl alcohol (PVAL). In some preparations, propylene glycol (PG) and thymol (TM) were also included as plasticizer and chemical absorption enhancer, respectively. Morphology, X-ray diffraction, spectroscopic, thermal, mechanical, and water uptake properties, as well as ex vivo permeability studies, were performed to characterize the film formulations. BZN remained stable and in an amorphous form over 90 days. The addition of PG and TM improved the mechanical properties of the films, making them soft, flexible and tear-resistant. Also, these additives increased the water sorption rate of the films at 50 and 75% relative humidity and the TM increased the film erosion properties and drug permeability (close to 6×) compared to control. It was hypothesized that the permeability improvement of thymol-based films that follow a drug release profile through erosion is also associated with the inhibition of the crystallization of BNZ when the film is in contact with the buccal mucosa. Once the thymol has previously demonstrated a significant in vivo and in vitro trypanocidal action and even improved film characteristics, these systems may be considered promising for Chagas' disease treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to verify the action of edible chitosan-citric acid (CHI-CA) coating to control Colletotrichum gloeosporioides and maintain quality parameters of fresh-cut guava. Chitosan was obtained from Litopenaeus vannamei shells using high temperature and short exposure times. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of CHI-CA against C. gloeosporioides were determined by macrodilutions at 28 °C/120 h in the absence/presence of CHI-CA (0-10 mg/mL). Scanning electron microscopy was used to evaluate morphological changes in the fungus. Guava slices were coated with CHI-CA (MIC) or 5 mg/mL glycerol (control). Rot incidence and physicochemical, physical, and microbiological factors were determined at 0, 3, 7, and 14 days at 24 °C and 4 °C. Chitosan presented typical structural characterization, 64% deacetylation, and a molecular weight of 1.6 × 10 4  g/mol. CHI-CA exhibited MIC and MFC values of 5 mg/mL and 10 mg/mL, respectively, and promoted changes in the morphology and cell surface of fungal spores. The fresh-cut guava coated with CHI-CA maintained quality parameters during storage and preserved their sensorial characteristics. Therefore, the use of CHI-CA as a coating is a promising strategy for improving postharvest quality of fresh-cut fruits., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Snakebites caused by Crotalus genus are the second most frequent in Brazil. Crotoxin is a beta-neurotoxin responsible for the main envenomation effects of Crotalus biting, while crotamine immobilizes the animal hind limbs, contributing to prey immobilization and to envenoming symptoms. As crotoxin and crotamine represent about 90% of Crotalus venom dry weight, these toxins are of great importance for antivenom therapy. In this sense, knowledge regarding the antigenicity/immunogenicity at the molecular level of these toxins can provide valuable information for the improvement of specific antivenoms. Therefore, the aims of this study are the identification of the B-cell epitopes from crotoxin and crotamine; and the characterization of the neutralizing potency of antibodies directed against the corresponding synthetic epitopes defined in the current study. Linear B-cell epitopes were identified using the Spot Synthesis technique probed with specific anti-C. d. terrificus venom horse IgG. One epitope of crotamine (F 12 PKEKICLPPSSDFGKMDCRW 32 ) and three of crotoxin (L 10 LVGVEGHLLQFNKMIKFETR 30 ; Y 43 CGWGGRGRPKDATDRCCFVH 63 and T 118 YKYGYMFYPDSRCRGPSETC 138 ) were identified. After synthesis in their soluble form, the peptides mixture correspondent to the mapped epitopes was entrapped in liposomes and used as immunogens for antibody production in rabbits. Anti-synthetic peptide antibodies were able to protect mice from the lethal activity of C. d. terrificus venom., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of OCT compound used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT compound also interferes with protein quantification assays, and that the presence of OCT compound impacts the quantification of extracted sphingolipids by LC-ESI-MS/MS. We developed and validated a simple and inexpensive method that removes OCT compound from OCT compound-embedded tissues. Our results indicate that removal of OCT compound from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC-ESI-MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer and to determine the long-term stability of sphingolipids in OCT compound-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT compound-cryopreserved normal lung tissues. This validated sphingolipidomic OCT compound-removal protocol should be a valuable addition to the lipid biologist's toolbox., (Copyright © 2020 Rohrbach et al.)

Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our molecular modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biological evaluation of a new series of compounds with inhibitory activity against both SphK1 and SphK2. These new inhibitors were obtained incorporating new connecting chains between their polar heads and hydrophobic tails. On the other hand, the combined techniques of molecular dynamics simulations and QTAIM calculations provided complete and detailed information about the molecular interactions that stabilize the different complexes of these new inhibitors with the active sites of the SphK1. This information will be useful in the design of new SphK inhibitors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: There is an increasing demand for accurately measured glomerular filtration rate (GFR). Iohexol serum clearance has become a new gold standard, but it is challenging when GFR is low and 24-hour sampling is required for accurate results. The primary aim of this study was to develop an iohexol pharmacokinetic population model for accurate determination of individual GFR using limited sampling for up to 5 hours also when renal function is <40 ml/min., Methods: A nonparametric iohexol population pharmacokinetic model was developed with rich data from 176 patients. In a validation cohort of 43 patients, a model-determined GFR (iohexol clearance) using different limited sampling strategies for up to 5 hours was compared with the strategy currently used in routine care, a log-linear 2-point method. In all, 1526 iohexol concentrations were used, from patients ranging in age from 1 to 82 years and GFR from 14 to 149 ml/min., Results: The clinical 2-point method showed insufficient agreement compared with reference values; 15% of GFR values had an error of greater than ±10% even when sampling for 24 hours when estimating GFR <40 ml/min per 1.73 m 2 (standard procedure). Restricted sampling the first 5 hours with the population model required 4 samples to determine GFR accurately. This strategy showed excellent agreement with the reference; <3% of GFR values had an error greater than ±10 %., Conclusion: Using an iohexol population pharmacokinetic model allows for accurate determination of GFR within 5 hours when applying 4 optimally timed samples, even in patients with GFR <40 ml/min., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)

We describe herein a chitosan nanocarrier for drug delivery applications obtained through the self-assembly of carboxymethyl-hexanoyl chitosan and dodecyl sulfate (CHC-SDS). Nanocapsules with spherical morphology were obtained in phosphate buffer at pH 7.4. These CHC-SDS nanocapsules showed no toxicity toward Jurkat cells (acute lymphoblastic leukemia) and were used to encapsulate a new pyrazoline (H3TM04) with antileukemia activity. The samples were characterized by dynamic light scattering (DLS) and Laser Doppler Micro-Electrophoresis. The encapsulation efficiency was higher than 96% (293.6 μg mL - 1 ) and the H3TM04-loaded nanocapsules (CHC-SDS-H) had a negative surface charge (-29.8 ± 0.7 mV) and hydrodynamic radius of around 84 nm. For the first time, CHC-SDS-H were formed and the antitumoral cancer activity was proved. The in vitro assays showed the controlled release of H3TM04 from the CHC-SDS-H nanocapsules in phosphate buffer pH 7.4. The H3TM04 release data were described by the power law model, indicating that H3TM04 delivery occurred via an erosion mechanism. The cytotoxicity assays with Jurkat and K-562 cells (acute myeloid leukemia) demonstrated that the CHC-SDS-H nanocapsule decreases the half maximal inhibitory concentration (IC 50 ). The study showed that CHC-SDS nanocapsules represent a promising nanocarrier for pyrazoline derivates that could be applied in leukemia therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The regioselective opening of the F ring of 22-oxo-23-spiroketals 7a-d using TiCl 4 in acetic anhydride yielded the novel furostanols 11a-d along with cholestanic derivatives 8a-d with pyranone E ring. The structures of the new derivatives thus obtained were established using one- (DEPT) and two-dimensional 1 H, 13 C NMR experiments (COSY, HSQC, HMBC, NOESY). The 22α-hydroxyl orientation in compounds 11a-d was proposed by comparison of the 13 C chemical shifts with those of other aglycone members of this family, and confirmed by combined NOESY and X-ray diffraction analysis of compound 11a., (Copyright © 2019. Published by Elsevier Inc.)

Rickettsia parkeri sensu stricto (s.s.) is an emerging human pathogen in the Americas. Comprehension of the etiology of R. parkeri infections in South America is complicated by the existence of genetic variants (Atlantic rainforest, NOD and Parvitarsum) of this species that are associated with specific groups of Amblyomma ticks. The rickettsial bacterium strain ApPR was first reported in Amblyomma parkeri ticks in Southern Brazil in 2012 and was considered, based on sequencing of fragments of the gltA, htrA, ompA and ompB genes, to represent yet another genetic variant of R. parkeri. In the current work, a multi-locus phylogenetic analysis employing additional genes and intragenic regions was performed using DNA extracted from (a) larvae of A. parkeri and Amblyomma species haplotype Nazaré ticks collected from wild birds, (b) a nymph of Amblyomma sp. haplotype Nazaré recovered from a monkey (Callicebus nigrifons), representing the first report of that tick parasitizing a non-human primate and (c) from a cultured isolate of ApPR, isolated from colony-reared adults of Amblyomma geayi. Phylogenetic inference performed using Maximum-likelihood (ML), Maximum Parsimony (MP) and Bayesian (B) methods, consistently placed strain ApPR outside the New World R. parkeri complex and instead grouped it in proximity to the Old World species Rickettsia africae and Rickettsia sibirica. Estimates of evolutionary divergence provided additional support for the inferred phylogenetic relationship. Given the clear evolutionary distance between strain ApPR and R. parkeri we propose the recognition of "Candidatus Rickettsia paranaensis"., (Copyright © 2019. Published by Elsevier GmbH.)

β-Sitosteryl (S)-ibuprofenate (2), stigmasteryl (S)-ibuprofenate (3), ergosteryl (S)-ibuprofenate (4), and cholesteryl (S)-ibuprofenate (5) were prepared in 70-75% yields by Steglich esterification and were characterized by 1D and 2D NMR, as well as by MS. The new esters were evaluated in in vivo pain models of antinociception and anti-inflammation using the writhing, formalin, and carrageenan tests, in mice and rats, and the results were compared with those of (S)-ibuprofen (1). Damage to the gastric mucosa of animals was also assessed. The results indicated that 2-5 have comparable or eventually better activity than 1 at the same mg/kg doses. Since the molecular weight ratio of esters 2-5 to ibuprofen is about 3-1, the amount of truly incorporated ibuprofen was roughly one third to achieve similar effects. This resulted in minimal gastrointestinal damage in the stomach of the animals, in contrast to the large gastric injury caused by (S)-ibuprofen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Kynureninase from Pseudomonas fluorescens (Pfkynase) catalyzes the pyridoxal-5'-phosphate (PLP) dependent hydrolytic cleavage of L-kynurenine to give anthranilate and L-alanine. Asp-132 and Asp-201 are located in the structure near the pyridine NH of the PLP, with Asp-201 forming a hydrogen bond. Mutation of Asp-132 to alanine and glutamate and Asp-201 to glutamate results in reduced catalytic activity with L-kynurenine and β-benzoyl-L-alanine, but not O-benzoyl-l-serine. D132A, D132E D201E and S36A mutant Pfkynases all can form quinonoid and vinylogous amide intermediates with β-benzoyl-L-alanine, similar to wild-type enzyme. D132A, D132E, and D201E Pfkynase react more slowly with β-benzoyl-L-alanine and benzaldehyde to form an aldol product absorbing at 490 nm than wild-type, with D132E reacting the slowest. The 1 H NMR spectra of wild-type and D201E Pfkynase are very similar in the low field region from 10 to 18 ppm, but that of D132A Pfkynase is missing a resonance at 13.1 ppm. These results show that these residues modulate the reactivity of the PLP at different stages during the reaction cycle. Ser-36 is located near the expected location of the carbonyl oxygen of the substrate. Mutation of Ser-36 to alanine results in a 230-fold reduction of k cat and 30-fold reduction in k cat /K m with L-kynurenine, but very little effect on the reaction of O-benzoyl-l-serine. Thus, the rate-determining step in the reaction of S36A Pfkynase is the C β -C γ bond cleavage. These results support the hypothesis that Ser-36 together with Tyr-226 is part of an oxyanion hole that polarizes the carbonyl of the substrate in the catalytic mechanism of Pfkynase., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The thermoxidation of biodiesel was monitored using different spectroscopic techniques: UV-Vis and MIR absorption, Raman spectroscopy, and visible fluorescence. As the oxidation progressed, the UV-Vis absorption spectra showed an increase in the spectral range between 34,000 and 26,000 cm -1 , while two main fluorescence bands (under ultraviolet excitation) were observed at around 21,000 and 15,000 cm -1 . The UV-Vis absorption and fluorescence intensities presented opposite behavior during the processes, irrespective of the temperature used (90, 140, or 190 °C). These effects could be explained by the consumption of natural antioxidants, followed by the formation of primary oxidation compounds. The Raman and MIR absorption results indicated the existence of a cis-trans isomerization effect, followed by the formation of hydroperoxides during the oxidation, with the behavior being the same as that revealed by the UV-Vis absorption and fluorescence analyses. The comparison, under the same conditions, of different spectroscopy techniques that can be used to monitor the stages of thermoxidation of soybean biofuel provides important information for selection of an appropriate technique for evaluating biodiesel integrity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To describe an outbreak of acute myalgia accompanied by elevated levels of muscle enzymes that occurred in the northeast region of Brazil from December 2016 through to May 2017., Methods: Clinical data were analysed and laboratory tests were performed in 86 specimens obtained from 52 individuals with suspected acute myalgia. A broader reactive enterovirus real-time RT-PCR followed by a semi-nested PCR amplification of partial VP1 gene were performed to identify the causative agent., Results: Eighty-six clinical samples were received in our laboratory during the myalgia outbreak. Median age of individuals was 39 years. Sudden acute myalgia and dark urine were the most common symptoms. Creatine phosphokinase levels were elevated with mean value ∼16 893 U/L. Human enterovirus was detected in 67% (58/86) of the patient's specimens (urine, serum, faeces and rectal swab). The enterovirus positivity per patient was 82.7% (43/52). Echovirus 30 (E-30) (82% of the typed specimens, 18/22; 76.4% (13/17) of the typed specimens per patient) was the main enterovirus identified. In addition to E-30, CV-A16 (1/22) and E-6 (3/22) were detected in 4% and 14% of the typed specimens, respectively. No deaths occurred., Conclusion: The 2016-2017 outbreak of acute myalgia that occurred in the northeast region of Brazil can be associated with E-30. Despite the clinical manifestations, a favourable outcome was observed for all patients., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The ingestion of detritus by sea turtles results in high mortality and morbidity. The objective of this study was to describe the characteristics of free-living sea turtles that ingested anthropogenic inorganic detritus in comparison to those that did not. A total of 186 necropsy files were analyzed in marine turtles from the beaches of the Microregion dos Lagos, Rio de Janeiro. Among the turtles that ingested detritus, the mean turtle was female and cachectic, with a carapace length of 36,6 cm, detritus accumulated in the large intestine, and fecal compaction. It seems most likely that's low food transit, combined with the multiplicity of ingestion, favored the accumulation of detritus. This ingestion resulted in cachexia associated with fecal compaction, since the greatest accumulation was in the large intestine. The intake of detritus by turtles was not punctual but continuous. These studies demonstrated the vulnerability of these animals to environmental pollution., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Our goal is to define patient navigation for an imaging audience, present a focused selection of published experiences with navigation programs for breast and colorectal cancer screening, and expose principal barriers to the success of such programs. Despite numerous advances in the early detection of cancers, many patients still present with advanced disease. A disproportionate number are low-income minority patients who experience worse health outcomes than their white or more financially stable counterparts. Patient navigation, which aims to assist the medically underserved by overcoming specific barriers to care, may represent one solution to narrowing disparities. Related research suggests that in general, patient navigation programs that have addressed breast or colorectal cancer screening have been successful in improving screening rates and timeliness of follow-up care. However, although beneficial, navigation is expensive and may present an unmanageable financial burden for many health care centers. To overcome this challenge, navigation efforts will likely need to target those patients that are most likely to benefit. Further research to identify such patients will be critically important for improving the sustainability of navigation programs, and, in turn, for realizing the benefits of such programs in reducing cancer disparities., (Copyright © 2018. Published by Elsevier Inc.)

Background: In Brazil, the Asemeia genus has 19 species (12 endemic) and 2 varieties (both endemic) and some of them are found in semi-arid Bahia., Objective: The objective of this study was to quantitatively determine identified substances by HPLC-DAD in Asemeia ovata extracts and to predict their biological activities in silico., Method: The quantification method by HPLC-DAD has been validated according to the guidelines of the International Conference of Harmonization. The prediction in silico activities was made by Target Fishing methods (TF), followed by docking by the program DOCK 6.7 and assessment of interaction profiles for Protein-Ligand Interaction Profiler server., Results: It was possible to identify and quantify using HPLC-DAD substances: rutin, luteolin-7-O-glucoside, caffeic acid, p-coumaric acid and trans-ferulic acid. The ChemProt 2.0 server was selected for TF method, which has shown potential activity of compounds on molecular targets such as Carbonic anhydrase 12, epidermal growth factor receptor and sodium-glucose cotransporter 2., Conclusion: This work provides new results for the species both from a biological and chemical point of view, and has interesting potential to be discovered with the prospect of further studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Thermal lens spectroscopy (TLS) in the near-near-infrared region was used to explore the absorptions of overtones and combination bands of sulfentrazone (SFZ) herbicide diluted in methanol. This spectroscopic region was chosen in order to guarantee that only thermal lens effect is noted during the experimental procedure. The results showed that it was possible to detect very low concentrations (~2ng/μL) of SFZ in methanol by determining its thermal diffusivity or the absorption coefficient due to the 3ν(NH)+1δ(CH) combination band. This minimum SFZ concentration is the limit observed by chromatography method. The findings demonstrated that the TLS can be used for precise and accurate assessment of pesticides in ecosystems. Besides, the 3ν(NH)+1δ(CH) combination band at 960nm can be used as a marker for SFZ in methanol., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while "late" inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nitric oxide (NO) is an important signaling molecule occurring in virtually all organisms, whose mechanism of action relies mainly on its interaction with proteins or peptides by nitrosylation, forming compounds such as S-nitrosothiols (SNO). The Saville reaction and the ozone-based chemiluminescence method are the main techniques used for nitrosylated protein quantification. While the Saville assay is not very sensitive, the ozone-based chemiluminescence is expensive and time-consuming. Here we propose a method in which the protein-bound NO groups are exposed to UV light, cleaving the bond and allowing the quantification of the derived NO molecules by diamino-rhodamine (DAR) dyes. The DAR-based method was shown to be specific in plant tissues by pre-treatment of the samples with reducing agents and parallel EPR analysis. Spike-and-recovery assays revealed 72% recovery after a GSNO spike. Moreover, the method was significantly more sensitive than the Saville reaction, and this increase in sensitivity was crucial for detecting the reduced levels of nitrosylated proteins in plant species other than Arabidopsis. The method presented here is a suitable alternative to compare plant samples, allowing simple and fast detection of nitrosylated proteins., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The pathological and molecular findings associated with Talaromyces marneffei-induced pneumonia with concomitant infection by canine distemper virus (CDV) are described in a dog. The principal pathological alteration occurred in the lungs. Histopathology confirmed multifocal granulomatous pneumonia associated with numerous intralesional and intracellular septate fission cells consistent with T. marneffei. A molecular assay designed to amplify a partial fragment of the 18S rRNA gene of T. marneffei provided positive results from two fungal cultures derived from the lung. Sequencing and phylogenetic analyses confirmed the results of polymerase chain reaction (PCR). Furthermore, antigens of the CDV N protein were identified within the bronchial epithelium by immunohistochemistry and a PCR assay amplified the CDV N gene from hepatic and pulmonary fragments. Collectively, the pathological and molecular techniques confirmed a diagnosis of T. marneffei-induced pneumonia with concomitant infection by CDV. These findings represent the first description of pulmonary penicilliosis in the dog and extend the geographical niche of this emerging infectious pathogen. In this case, infection by CDV may have induced immunosuppression, which facilitated the development of pulmonary penicilliosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The main goal of this study was to examine the relationship among burnout, engagement, well-being, and academic performance in Portuguese secondary school pupils. The existence of gender related differences in these relationships was also investigated. The sample was composed of 489 pupils who attended an academic track at secondary school. Results of multi-group structural equation modelling indicated that higher levels of cynicism towards studies were associated with lower academic achievement. Exhaustion was not uniquely related to the adolescents' academic achievement or well-being. However, higher levels of engagement, namely dedication and vigour, were related to higher levels of well-being. Moreover, vigour was also uniquely associated with academic achievement. The results were similar for boys and girls. Implications for intervention and future research are discussed., (Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Purpose: Diagnostic chest CT frequently results in abnormal findings that require follow-up. We assessed the timeliness of follow-up after CT abnormalities were identified in symptomatic smokers at high risk for developing lung cancer., Methods: In an academic primary care network, we identified current smokers aged 55-79 years who received a diagnostic chest CT to evaluate symptoms during 2012. Medical chart abstraction identified radiologist recommendations and follow-up care. The outcome was the proportion of patients who received timely follow-up (within 30 days of recommendation) after an abnormal chest CT. We assessed for predictors of compliance with recommended follow-up., Results: Of 3,257 eligible smokers, 446 (14%) had a chest CT during 2012. We excluded 70 patients who already had lung cancer, died, had imaging done elsewhere, or left the practice. Of the remaining 376 patients, 337 (90%) had abnormal chest CT findings, and 184 (55%) had a specific follow-up recommendation. Among those with recommended follow-up, only 102 of 184 (55%) had timely follow-up. Those who had a CT performed to evaluate pulmonary disease and those receiving care in community health centers were more likely to receive timely follow-up. Of 27 patients newly diagnosed with lung cancer, 18 (67%) had their first oncology visit within 30 days of diagnosis., Conclusions: Among patients undergoing diagnostic chest CTs, most received follow-up for abnormal findings, but it was often delayed. Systems to support patients in obtaining recommended follow-up are needed to ensure that the benefits of lung cancer screening translate into usual clinical practice., (Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The sentinel node has a fundamental role in the management of early breast cancer. Currently, the double detection of blue and radioisotope is recommended. But in common practice, many centers use a single method. However, with a single detection, the risk of false negatives and the identification failure rate increase to a significant extent and the number of sentinel lymph node detected and removed is not enough. Furthermore, the tracers used until now show inconveniences. The purpose of this work is to present a new method of detection, using the green of indocyanine coupled with fluorescence imaging, and to compare it with the already existing methods. The method combined by fluorescence and isotopic is reliable, sure, of fast learning and could constitute a good strategy of detection. The major interest is to obtain a satisfactory number of sentinel nodes. The profit could be even more important for overweight patients. The fluorescence used alone is at the moment not possible. Wide ranging studies are necessary. The FLUOTECH, randomized study of 100 patients, comparing the isotopic method of double isotope technique and fluorescence, is underway to confirm these data., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Glioblastoma is characterized by constitutive apoptosis resistance and survival signaling expression, but paradoxically is a necrosis-prone neoplasm. Incubation of human U118 glioblastoma cells with the antitumor alkylphospholipid analog edelfosine induced a potent necrotic cell death, whereas apoptosis was scarce. Preincubation of U118 cells with the selective MEK1/2 inhibitor U0126, which inhibits MEK1/2-mediated activation of ERK1/2, led to a switch from necrosis to caspase-dependent apoptosis following edelfosine treatment. Combined treatment of U0126 and edelfosine totally inhibited ERK1/2 phosphorylation, and led to RIPK1 and RelA/NF-κB degradation, together with a strong activation of caspase-3 and -8. This apoptotic response was accompanied by the activation of the intrinsic apoptotic pathway with mitochondrial transmembrane potential loss, Bcl-xL degradation and caspase-9 activation. Inhibition of ERK phosphorylation also led to a dramatic increase in edelfosine-induced apoptosis when the alkylphospholipid analog was used at a low micromolar range, suggesting that ERK phosphorylation acts as a potent regulator of apoptotic cell death in edelfosine-treated U118 cells. These data show that inhibition of MEK1/2-ERK1/2 signaling pathway highly potentiates edelfosine-induced apoptosis in glioblastoma U118 cells and switches the type of edelfosine-induced cell death from necrosis to apoptosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The estrogen receptors (ESRα and β) and the androgen receptor (AR) mediate genomic and non-genomic effects on breast tumor growth and proliferation. We analyzed 101 breast cancer patients for allelic loss in microsatellites located in regulatory regions of the ESRs and AR genes in breast cancer tumors. The loss of heterozygosity (LOH) at these loci was found in 36.2% of tumor tissues (ductal carcinoma cases), for 19% of cases at the ESRα locus, for 16% at the ESRβ locus, and for 10% at the AR locus. The LOH in at least one of the two ESR loci was correlated to poor prognosis criteria: ESR-negative status (P = 0.007), PR-negative status (P = 0.003), high Scarff-Bloom-Richardson (SBR) grade (P = 0.0007), high MIB-1 proliferation index (P = 0.02), and diminished apoptosis potential (TP53-positive status, P = 0.018). When AR was also considered, the LOH in at least one of the three loci was associated with ESR-negative status (P = 0.036), PR-negative status (P = 0.027), high SBR grade (P = 0.005), high mitotic index (P = 0.0002), TP53-positive status (P = 0.029), and proliferating index (high MIB-1, P = 0.03). Allelic loss was observed in 26% of normal tissue adjacent to tumor with LOH at the ESRα locus and in 7.1% of tumors with LOH at the ESRβ locus. The LOH in tumor tissue in the regulatory regions of ESRα, ESRβ, and AR genes has potentially synergistic effects on tumor proliferation, histological aggressiveness, down-regulation of ESRα and progesterone receptor (PR) genes, and is an early genetic alteration in cancer that is possibly involved in passage to estrogen independence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the present paper the synthesis and optical characterization of iodinated acetophenone, 4-hydroxy-3-iodoacetophenone and 4-hydroxy-3,5-diiodoacetophenone obtained from 4-hydroxyacetophenone, were carried out. The optical features of iodinated molecules were determined by performing the UV-Vis absorption, fluorescence and thermal lens spectroscopies. The results showed that the optical properties of the 4-hydroxyacetophenone is altered when the iodine atom is inserted, as substituent, in the aromatic ring. Although it was determined that the optical feature was changed when one iodine atom was inserted in the aromatic ring (4-hydroxy-3-iodoacetophenone), the results revealed that emission behavior was strongly altered when two iodine atoms (4-hydroxy-3,5-diiodoacetophenone) were acting as substituents: the fluorescence quantum efficiency increases approximately 60%., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Switching to cyclosporine A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown., Methods: Obese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3mg/kg/day) until diabetes development; then: (a)22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b)22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and were used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study., Results: β-cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day 12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day 12 group, rats in tacrolimus-cyclosporin group showed an increased β-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable., Conclusion: An early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased β-cell proliferation and reversion of diabetes in 50% of cases., (Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Tenodesis of the long head of the biceps tendon (LHB) at the upper part of the bicipital groove has been related to persistent postoperative bicipital pain. This is possibly due to the inflammation of the remaining tendon within the groove. This, in turn, could be attributed to the continual mechanical stress placed on the tendon in the narrow bicipital groove. Theoretically, should the LHB be more "relaxed," the mechanical stress applied on it would be diminished. On the basis of this rationale, we present an arthroscopic biceps tenodesis technique, according to which the tendon is fixed at the entrance of the bicipital groove, using a bioabsorbable screw, relaxed by 5 mm. In this lax position, the residual LHB tension is expected to be decreased compared with the initial tension, whereas no cosmetic deformity (Popeye sign) or impaired muscular performance is anticipated.

Sphingosine kinases (SphKs), of which there are two isoforms, SphK1 and SphK2, have been implicated in regulation of many important cellular processes. We have developed an assay for monitoring SphK1 and SphK2 activity in real time without the need for organic partitioning of products, radioactive materials, or specialized equipment. The assay conveniently follows SphK-dependent changes in 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled sphingosine (Sph) fluorescence and can be easily performed in 384-well plate format with small reaction volumes. We present data showing dose-proportional responses to enzyme, substrate, and inhibitor concentrations. The SphK1 and SphK2 binding affinities for NBD-Sph and the IC50 values of inhibitors determined were consistent with those reported with other methods. Because of the versatility and simplicity of the assay, it should facilitate the routine characterization of inhibitors and SphK mutants and can be readily used for compound library screening in high-throughput format., (Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.)