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A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

Introduction: Even though the prevalence rate of diabetes in Portugal is one of the highest in Europe, no studies on the association between patient centered medicine, diabetes self-care, and glycemic control have been published. Assuming that patient centered medicine increases adherence to treatment through the improvement of the doctor-patient relationship, the aim of this study was to assess the influence of patient-centered medicine on the self-care of patients with type 2 diabetes patients’ (T2DM) in two Family Health Units in Central Portugal, according to gender and age.Material and Methods: A cross-sectional study was conducted in two Family Health Units in Central Portugal between the 25th November 2021 and the 15th January 2022. Patients with type 2 diabetes were invited to fill in the Patient-Centered Medicine questionnaire, for patients (PCM-p) (where higher values represent worse results) and the Summary of Diabetes Self-Care Activities Measure (SDSCAM), (where higher values represent better results), while healthcare professionals filled in the epidemiologic variables on pre-defined days.Results: A sample of 298 patients with type 2 diabetes was studied. Linear regressions for the association between SDSCAM scale factors and PCM-p showed significant associations for general diet (β = -0.07, p < 0.001), specific diet (β = -0.10, p < 0.001), exercise (β = -0.03, p = 0.008), foot care (β = -0.11, p < 0.001) and medication adherence in general (β = -0.06, p = 0.001). Multiple linear regression including the association between glycated hemoglobin (HbA1c) and the SDSCAM scale dimensions showed that specific diet was associated with lower HbA1c levels (β = -0.01, p = 0.007) and blood sugar testing (β = 0.01, p < 0.001) and that a higher score in PCMp was associated with higher HbA1c levels (β = 0.06, p < 0.001). Male patients (β = -6.93, p = 0.007) and older patients (β = -0.42, p = 0.001) were associated with lower scores in the specific diet. The male gender was associated with higher scores in exercise (β = 7.62, p = 0.029), lower scores in foot care (β = -6.06, p = 0.029) and lower scores in medication adherence to injectable medicines/6.2 (β = -0.73, p = 0.018). Age was associated with a lower score in medication (β = -0.03, p = 0.045) and a higher PCMp total score (β = 0.07, p = 0.030).Conclusion: Patient-centered medicine in type 2 diabetics is associated with better self-care behaviors in patients with type 2 diabetes. Gender and age differences were observed in self-care behaviors and age differences were observed in Patient Centered Medicine.

Hair care and treatment has evolved significantly through the years as new formulations are continuously being explored in an attempt to meet the demand in cosmetic and medicinal fields. While standard hair care procedures include hair washing, aimed at hair cleansing and maintenance, as well as hair dyeing and bleaching formulations for hair embellishment, modern hair treatments are mainly focused on circumventing hair loss conditions, strengthening hair follicle properties and treat hair infestations. In this regard, active compounds (ACs) included in hair cosmetic formulations include a vast array of hair cleansing and hair dye molecules, and typical hair treatments include anti-hair loss ACs (e.g. minoxidil and finasteride) and anti-lice ACs (e.g. permethrin). However, several challenges still persist, as conventional AC formulations exhibit sub-optimal performance and some may present toxicity issues, calling for an improved design of formulations regarding both efficacy and safety. More recently, nano-based strategies encompassing nanomaterials have emerged as promising tailored approaches to improve the performance of ACs incorporated into hair cosmetics and treatment formulations. The interest in using these nanomaterials is based on account of their ability to: (1) increase stability, safety and biocompatibility of ACs; (2) maximize hair affinity, contact and retention, acting as versatile biointerfaces; (3) enable the controlled release of ACs in both hair and scalp, serving as prolonged AC reservoirs; besides offering (4) hair follicle targeting features attending to the possibility of surface tunability. This review covers the breakthrough of nanomaterials for hair cosmetics and hair treatment, focusing on organic nanomaterials (polymer-based and lipid-based nanoparticles) and inorganic nanomaterials (nanosheets, nanotubes and inorganic nanoparticles), as well as their applications, highlighting their potential as innovative multifunctional nanomaterials towards maximized hair care and treatment. STATEMENT OF SIGNIFICANCE: This manuscript is focused on reviewing the nanotechnological strategies investigated for hair care and treatment so far. While conventional formulations exhibit sub-optimal performance and some may present toxicity issues, the selection of improved and suitable nanodelivery systems is of utmost relevance to ensure a proper active ingredient release in both hair and scalp, maximize hair affinity, contact and retention, and provide hair follicle targeting features, warranting stability, efficacy and safety. This innovative manuscript highlights the advantages of nanotechnology-based approaches, particularly as tunable and versatile biointerfaces, and their applications as innovative multifunctional nanomaterials towards maximized hair care and treatment.

Neospora caninum, an apicomplexan parasite, is the etiological agent of neosporosis, a disease that leads to neurological symptoms in dogs and abortion in cattle. Vaccine or drug treatments for neosporosis remain to be determined. Therefore, it is of undeniable relevance to investigate new molecules involved in the parasite's successful survival within the host cell. The aim of this study was to characterize the N. caninum peroxiredoxin (NcPrx), an enzyme involved in the redox system of the parasite. The NcPrx amino acid sequence showed high identity and similarity compared to homologues representatives of Apicomplexa phylum. The recombinant NcPrx (rNcPrx) was cloned and expressed in Escherichia coli (BL21) with the predicted molecular weight (22 kDa), and the identity of monomer and dimer forms of rNcPrx was confirmed by mass spectrometry. Native and recombinant NcPrx were detected by ELISA and western blot, using the polyclonal anti-rNcPrx serum. Multiphoton analysis showed that NcPrx is localized in tachyzoite cytosol. H

The prevalence of oxidative and inflammatory stress in end-stage renal disease (ESRD) patients has often been associated with chronic haemodialysis therapies. Over the past decades, several reports have shown the potential of hydrogen molecule as an antioxidant in the treatment of various medical conditions in animal models, as well as in pilot studies with human patients. Recently, a hydrogen-enriched dialysate solution has been introduced, holding promise in reducing the oxidative and/or inflammatory complications arising during haemodialysis. To this end, a standardised measuring method to determine the levels of hydrogen in dialysate and subsequently in blood is required. This study explores the possibility of quantifying hydrogen concentration using a novel contactless sensor that detects dissolved hydrogen in liquids. An experimental circuit is assembled to validate the sensitivity and accuracy of the hydrogen monitoring system (Pureron Japan Co., Ltd) through in vitro investigations with physiological solutions. Measurements of dissolved molecular hydrogen concentration are corroborated by an established oxygen sensor providing continuous partial pressure readings. The relationship between the applied H2 content in the gaseous mixture and the H2 concentration value at equilibrium is linear. At the same time, the hydrogen monitoring system has a rather long response time, and its readings seem to slightly diverge from sensor to sensor as well as at different temperatures. For this reason, a sensor recalibration might be necessary, which could become part of the product’s ongoing development. Nevertheless, the aforementioned minor deficiencies can be mostly considered negligible in applications such as haemodialysis.

The octanol-water partition coefficient of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) was investigated using atomistic molecular dynamics simulations via thermodynamic integration and multistate Bennett acceptance ratio methods. The GAFF and CHARMM36 force fields were used with six water models widely used in molecular dynamics simulations. The OPC4 water model provided the best agreement with the experimental octanol-water partition coefficient of DPPC using the two force fields. However, there is still plenty of room for improvement in water models with correct estimation of surface tension that uses better and suitable non-bonded interaction parameters between water-water and water-DPPC. The Gibbs free energy of transferring DPPC from octanol to water phase was calculated to be 19.8 ± 0.3 and 20.2 ± 0.3 kcal mol−1, giving a partition coefficient of 14.5 ± 0.4 and 14.8 ± 0.3 for the GAFF and CHARMM36 force fields, respectively. This study reinforces the importance of developing new water models that reproduce experimental surface tensions to reconcile the water-water and water-DPPC non-bonded interactions and the existing discrepancy between experimental measurements of amphiphilic molecules that are important in many areas of scientific applications and industry such as biophysics, surfactant, colloids, membranes, medicine, nanotechnology, and food and pharmaceutical industries, and so on. It raises two important open questions: Is the experimental octanol-water partition coefficient of DPPC reliable? Or is its calculation accurate using the OPC4 water model? With respect to the experimental measurements, there may be non-treated aspects such as the formation of aggregates in aqueous phase and limit of detection of the applied method. And, in the calculation, some effects are not possible to be considered in a correct way or viable time such as calculating quantum effects, sampling all conformations, considering phase transitions, and correctly evaluating the intermolecular forces to estimate an accurate surface tension. Communicated by Ramaswamy H. Sarma

Resumo Objetivo Estudar a anatomia do ligamento coracoclavicular medial e avaliar a contribuição do ligamento acromioclavicular, coracoclaviculares e coracoclavicular medial na estabilidade da articulação acromioclavicular. Métodos Foram dissecados 26 ombros de 16 cadáveres frescos, posicionados em decúbito dorso-horizontal, com um coxim de 15 cm de altura entre as escápulas. Realizou-se uma via deltopeitoral estendida proximal e medialmente. Realizou-se dissecção por planos e identificação dos ligamentos. Realizou a medida da distância acromio-clavicular e coracoclavicular usando pontos previamente demarcados com paquímetro milimetrado. Em seis dessas amostras foi realizado estudo biomecânico. Seccionando, nesta ordem, o ligamento acromioclavicular, os coracoclaviculares e o ligamento coracoclavicular medial com uma força cefálica de 20N foi aplicada na clavícula lateral. Foi medida a distância acromio-clavicular e coracoclavicular em cada uma das etapas de secção dos ligamentos. Resultados A média de comprimento do ligamento coracoclavicular medial foi de 48,9mm e a média de largura, de 18,3mm no lado direito. No esquerdo, a média de comprimento foi de 48,65mm e a média da largura, 17,3mm. Após a secção dos ligamentos acromioclaviculares, coracoclaviculares, com a secção do ligamento coracoclavicular medial houve aumento estatisticamente significativo da distância córaco-clavicular e um deslocamento posterior da escápula. Conclusão O ligamento coracoclavicular medial é uma estrutura ligamentar verdadeira, presente em todos os ombros dissecados. Nossos resultados demonstraram que o ligamento coracoclavicular medial encontra-se relaxado com a escápula em protração e tenso com a escápula em retração e segundo nossos resultados participa tanto da estabilidade vertical quanto da estabilidade horizontal da articulação acromioclavicular.

Tese no âmbito do Doutoramento em Construcao Metalica e Mista orientada pelo Professor Doutor Rui Antonio Duarte Simoes e apresentada ao Departamento de Engenharia Civil da Faculdade de Ciencias e Tecnologias da Universidade de Coimbra.

A reciclagem de baterias usadas tem suscitado preocupações de saúde pública uma vez que esta atividade está associada à exposição ocupacional e ambiental ao chumbo. Descreve-se o caso de uma mulher de 26 anos que iniciou quadro de palpitações associado a cefaleias, fadiga e insónias, cerca de quatro meses após iniciar funções numa empresa de reciclagem de baterias. Analiticamente, observou-se anemia (Hb 11,9 g/dL) e plumbémia de 59 μg/dL. Cessou funções na empresa e, após um mês, referiu uma diminuição progressiva da sintomatologia. O estudo analítico revelou uma normalização dos valores da hemoglobina (12,2 g/dL) e uma diminuição do valor de chumbo no sangue para 23,4 μg/dL. Os efeitos na saúde da exposição ao chumbo são inespecíficos e o seu diagnóstico requer um alto grau de suspeição. Neste âmbito revela-se importante a articulação entre o médico assistente e os serviços de Saúde, Higiene e Segurança no Trabalho das empresas.

This study aimed to determine the most and least important reasons for engaging in physical education classes among students in two educational pathways within the context of intrinsic and extrinsic motivation. Forty-one students participated in the study (25 males and 16 females; mean age = 16.37 ± 0.829). The sample was divided based on two class types: regular education and professional education. All students answered a questionnaire that aimed to verify the most and least important reasons for students to engage in physical education classes concerning intrinsic and extrinsic motivation. Indicated that both regular education and professional education classes had intrinsic and extrinsic motivation. The results also revealed that the participation of students was based essentially on their intrinsic motivation, but for different reasons when comparing the two educational pathways. Both types of the class were intrinsically and extrinsically motivated to participate in physical education classes.

Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.

We report the first occurrence of Bessierus doloris in Brazil. Additionally, we provide biological and taxonomic information on this species. Male imagos specimens were collected with a Pennsylvania light trap in the Apiaú region, municipality of Mucajaí, Roraima. The discovery of this species in Brazil extends its geographic distribution further west in South America, reaching about 100 meters in altitude above sea level.

Aim: We evaluated the diagnostic accuracy of ultrasound, postmortem and genetic studies in classifying skeletal dysplasias in the first vs second trimester of pregnancy. Methods: We retrospectively...

Osteosarcoma(OS) represents the main cancer affecting bone tissue, and one of the most frequent in children. In this review we discuss the major pathological hallmarks of this pathology, its current therapeutics, new active biomolecules, as well as the nanotechnology outbreak applied to the development of innovative strategies for selective OS targeting. Small RNA molecules play a role as key-regulator molecules capable of orchestrate different responses in what concerns cancer initiation, proliferation, migration and invasiveness. Frequently associated with lung metastasis, new strategies are urgent to upgrade the therapeutic outcomes and the life-expectancy prospects. Hence, the prominent rise of micelleplexes as multifaceted and efficient structures for nucleic acid delivery and selective drug targeting is revisited here with special emphasis on ligand-mediated active targeting. Future landmarks toward the development of novel nanostrategies for both OS diagnosis and OS therapy improvements are also discussed.

The interactions of the antiviral pentapeptide ATN-161 with the closed and open conformations of the α5β1 integrin, the SARS-CoV-2 major protease, and the omicron variant spike protein complexed with hACE2 were studied using molecular docking and molecular dynamics simulation. Molecular docking was performed to obtain ATN-161 binding poses with these studied protein targets. Subsequently, molecular dynamics simulations were performed to verify the ligand stability at the binding site of each protein target. Pulling simulations, umbrella sampling, and weighted histogram analysis method were used to obtain the potential of mean force of each system and calculate the Gibbs free energy of binding for the ATN-161 peptide in each binding site of these protein targets. The results showed that ATN-161 binds to α5β1 integrin in its active and inactive form, binds weakly to the omicron variant spike protein complexed with hACE2, and strongly binds to the main protease target. Communicated by Ramaswamy H. Sarma

Introduction: The objective of this study is to show the benefits of Meditation practice for young people with Autistic Spectrum Disorder. Method: The intervention study lasted for nine months, including two cycles, one of 8 weeks, and one of 4 months. Participants (n = 8; male = 7, female = 1) with average age of 21.5 years old (SD = 4.37). During both cycles, a weekly session of Meditation, which consisted of Mindfulness and Mantras exercises, was conducted in the center’s classroom, where the sample was following an administrative course. The participants were all invited to practice at home the different exercises when waking up and before sleeping for approximately 15 minutes. At the end of both cycles, we conducted semi-structured qualitative interviews with each participant, one of their closest family members, and their staff members from the center. Field notes were written at the end of each session. Results: Five out of the eight participants practiced at home, the practice became part of a habit for them. Those were the most susceptible to show results in stress and anxiety reduction, an increase in focuses, better emotional control, more pro-social behavior at home, and in the classroom. Discussion: We assume that family interest in the practice had an impact on the adherence of the participant to the program and consequence in better results. The participants who adopted our program as part of their daily life routine have shown results in a reduction of stress and anxiety and a better focus, prosocial improvements in the class environment, and better communication at home with family members.

Computer-mediated communication allows people to communicate across several contexts (e.g., friends, professional settings) by using video-based or text-based channels. In the latter case, communication lacks nonverbal cues (e.g., tone of voice) that are critical to message interpretation. Including emoji can help express emotion and reinforce or clarify the meaning of a message. However, the benefits of using emoji are likely to depend on the context (e.g., the relationship between interlocutors) and the messages' features (e.g., the valence of the message). To date, studies have not systematically and empirically examined how the use of emoji is perceived across different communication scenarios. In the current study, we asked 175 participants (49.5 percent women; Mage = 36.32, SD = 12.22) to imagine receiving either a negative or a positive message from 22 senders (e.g., friend; bank manager) and to indicate, for each case, how much they would like to receive an emoji and how useful and appropriate they considered the use of emoji. These ratings were combined into a single index of emoji use adequacy. Based on factor analysis, the 22 scenarios were aggregated in distant and close scenarios. Overall, results showed that participants considered emoji use more inadequate in distant (vs. close) scenarios and for negative (vs. positive) messages. These findings suggest that the perceived benefits of emoji use for text-based communication may not be generalized to all text-based communication contexts, such that relationship proximity and message valence should not be overlooked. Implications for the fields of consumer psychology and communication are discussed. info:eu-repo/semantics/acceptedVersion

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Myeloproliferative neoplasms (MPN) are hematological disorders characterized by increased proliferation of precursor and mature myeloid cells. MPN patients may present driver mutations in JAK2, MPL, and CALR genes, which are essential to describe the molecular mechanisms of MPN pathogenesis. Despite all the new knowledge on MPN pathogenesis, many questions remain to be answered to develop effective therapies to cure MPN or impair its progression to acute myeloid leukemia. The present study examined the expression levels of the Hippo signaling pathway members in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), as well as the role that they play in disease pathogenesis. The Hippo pathway is a tumor suppressor pathway that participates in the regulation of cell proliferation, differentiation, and death. Our main findings were: (i) expression of tumor suppressor genes from Hippo pathway were downregulated and seemed to be associated with cell resistance to apoptosis and increased proliferation rate; and (ii) Hippo pathway-related gene expression was associated with mutation status in ET and PMF patients. Therefore, the decreased expression of Hippo pathway-related genes may contribute to the malignant phenotype, apoptosis resistance, and cell proliferation in MPN pathogenesis.

Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/β-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.

Plants commonly interact with microorganisms that may influence their physiology and performance. Epiphytic yeasts are microorganisms that can be found in the phylosphere, in significantly larger numbers in fruits than in other plant tissues due to their higher nutritional content. The present study aimed to contribute to knowledge of epiphytic yeasts associated with Eugenia dysenterica DC. fruits and to evaluate their antimicrobial activity against phytopathogens. E. dysenterica fruits were collected, washed in saline solution, and sonicated. Each fruit solution was plated in three Petri dishes with NYDA medium. Yeast identification was performed through morphological and physiological criteria, and richness evaluation was performed using the Jackknife 1 estimator. All isolated yeasts were tested for diffusible substances against three phytopathogenic fungi. Only four of 42 isolates were inhibited sporulation of Aspergillus parasiticus, but none was able to inhibit or diminish mycelium growth of any tested phytopathogen. The present study contributes to the characterization of the E. dysenterica microbiome, presenting the first report of in vitro A. parasiticus sporulation inhibition by epiphytic yeasts and suggesting their promising use in biological control of this phytopathogen.

Resveratrol (RES), also known as 3,5,4'-trihydroxystilbene, is a polyphenolic phytoalexin that has been widely researched in the past decade due to its recognized numerous biological activities. Despite the potential benefits of RES, its effective use is limited due to its poor solubility, photosensitivity and rapid metabolism, which strongly undermine RES bioavailability and bioactivity. Thereby, recently, nanotechnology appeared as a potential strategy to circumvent RES physicochemical and pharmacokinetics constrains. However, only few studies have addressed the crucial in vivo suitability of the developed delivery systems to improve RES efficacy. Facing this scenario, in the present review, it is intended to present and discuss the in vivo resveratrol bioavailability and bioactivity, following its encapsulation or conjugation in nanotechnology-based carriers, contemplating their pharmacokinetics effectiveness.

Chagas disease is a tropical illness caused by the protozoanTrypanosoma cruzi. The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti-T. cruzieffects of phenothiazinium dyes in amastigote and trypomastigote forms of the parasite. Methylene Blue, New Methylene Blue, Toluidine Blue O, and 1,9-Dimethyl Methylene Blue inhibited the parasite proliferation at nanomolar concentrations and also demonstrated low toxicity in host cells. Moreover, combinations of phenothiazinium dyes indicated a synergic pattern against amastigotes compared to the Benznidazole counterparts. Phenothiazinium dyes levels of reactive oxygen species (ROS) and decreased the mitochondrial potential in trypomastigotes, indicating the mechanism of action of the dyes inT. cruzi. Our article offers a basis for future strategies for the control of Chagas disease using low-cost formulations, an important point for endemic underdeveloped regions.

Neospora caninum is an obligate intracellular parasite related to abortion in cattle, goats and sheep. The life cycle of N. caninum is characterized by the time-coordinated secretion of proteins contained in micronemes, rhoptries and dense granules, allowing the active invasion and the adaptation of the parasite in the cell environment. Thus, the proteins of the secretome have the potential to be considered as targets for N. caninum control. Despite the importance of neosporosis in the livestock-related economy, no commercial treatment is available. Furthermore, the process of invasion, propagation and immune evasion are not completely elucidated. In this study, we initiated the characterization of NCLIV_011700 of N. caninum, a protein with low sequence identity to NcROP15 or TgROP15 (15%). Our goal was the detection and molecular characterization of the NCLIV_011700, once homology (with low identity20%) was observed within the Apicomplexa. The NCLIV_011700 sequence was aligned and compared to the closer apicomplexan homologues (ROP15 from N. caninum, T. gondii, Hammondia hammondi, Cystospores suis), including the predicted domains. In general, the NCLIV_011700 demonstrated low identity with ROP15 of apicomplexan (20%) and had a ubiquitin domain. On the other side, the NCLIV_011700 homologues were composed of a non-cytoplasmic domain, suggesting different functions between NcROP15 (or homologues) and NCLIV_011700 during the parasite life cycle. Moreover, the NCLIV_011700 was amplified by PCR, ligated to a pET28a plasmid and expressed in Escherichia coli. The recombinant form of NCLIV_011700 was purified in a nickel-Sepharose resin and applied for polyclonal antibody production in mice. The antiserum against NCLIV_011700 (anti-rNCLIV_011700) was used to localize the native form of the protein using Western blot and confocal microscopy. Also, the NCLIV_011700 antiserum partially inhibited the parasite adhesion/invasion process, indicating an active role of the protein in the N. caninum cycle. Thus, the initial NCLIV_011700 characterization will contribute to enlarging the comprehension of N. caninum, aiming at the future development of tools to control the parasite infection/propagation.

Neospora caninum causes heavy losses related to abortions in bovine cattle. This parasite developed a complex defense redox system, composed of enzymes as glutathione reductase (GR). Methylene blue (MB) impairs the activity of recombinant form of Plasmodium GR and inhibits the parasite proliferation in vivo and in vitro. Likewise, MB and its derivatives inhibits Neospora caninum proliferation, however, whether the MB mechanism of action is correlated to GR function remains unclear. Therefore, here, N. caninum GR (NcGR) was characterized and its potential inhibitors were determined. NcGR was found in the tachyzoite cytosol and has a similar structure and sequence compared to its homologs. We verified the in vitro activity of rNcGR (875 nM) following NADPH absorbance at 340 nM (100 mM KH2PO4, pH 7.5, 1 mM EDTA, ionic strength: 600 mM, 25 °C). rNcGR exhibited a Michaelian behavior (Km(GSSG):0.10 ± 0.02 mM; kcat(GSSG):0.076 ± 0.003 s-1; Km(NADPH):0.006 ± 0.001 mM; kcat(NADPH): 0.080 ± 0.003 s-1). The IC50 of MB,1,9-dimethyl methylene blue, new methylene blue, and toluidine blue O on rNcGR activity were 2.1 ± 0.2 μM, 11 ± 2 μM, 0.7 ± 0.1 μM, and 0.9 ± 0.2 μM, respectively. Our results suggest the importance of NcGR in N. caninum biology and antioxidant mechanisms. Moreover, data presented here strongly suggest that NcGR is an important target of phenothiazinium dyes in N. caninum proliferation inhibition.

Background The use of immunosuppressive and antifibrotic agents for the treatment of chronic hypersensitivity pneumonitis (CHP) appears promising, but there is still no evidence supporting the clinical decision regarding the implementation of each specific pharmacological strategy. Methods Patients diagnosed with CHP and treated with azathioprine (AZA) were retrospectively selected from a single centre for Interstitial Lung Diseases. Baseline clinical data, as well as functional, imaging, bronchoalveolar lavage (BAL) and histology features were assessed. Longitudinal data on functional parameters were collected and comparatively analysed with patients' characteristics. Results In this cohort of 80 patients, of those who reached 12 months of treatment, 78.3% presented a preserved forced vital capacity, with 59 being eligible to be classified as AZA responders (n = 36) or non-responders (n = 23). BAL lymphocytosis was associated with a favourable response to AZA treatment (OR 1.051; 95% CI 1.015–1.089), although it didn't identify all responders. Conclusions AZA revealed to be effective in disease stabilisation in most patients, while ineffective for a subset. BAL lymphocytosis appears as a potentially valuable strategy to identify AZA responders, although with limited accuracy. Further studies are needed to clarify other response markers to immunosuppressive agents, in order to optimize the therapeutic options for this condition.

A 26-year-old woman (patient 1 on the family tree—figure 1) gave a 6-year history of dysarthria, occasional jerks and progressive gait unsteadiness with frequent falls, and had become bedridden. On examination, she had dorsal kyphosis and pes cavus. There was severe truncal and appendicular ataxia, generalised action myoclonus, hyporeflexia, hypotonia and bilateral extensor plantar reflexes. Electromyography with nerve conduction studies identified a sensorimotor polyneuropathy, with intermediate conduction velocities. Figure 1 Family tree depicting genetic and phenotypic status of the family members. Her medical history was unremarkable, with a normal development. She had experienced one recent generalised tonic–clonic seizure. She had an older sister (patient 2 on the family tree—figure 1) with a rapidly progressive nephrotic syndrome starting at the age of 17, becoming steroid resistant and needing haemodialysis after a few months. She also had a normal development and unremarkable medical history. At age of 21, she had developed action myoclonus of the lower limbs, with subjective loss of strength and frequent falls, later progressing to the upper limbs. She started having generalised tonicclonic seizures and lost walking ability in the next year. At aged 28 years, she underwent renal transplantation and died 5 years later due to graft-related complications. Their parents were consanguineous (they were half-siblings) and they had a healthy sister. ### How can you localise her myoclonus and what should be the initial steps in the evaluation? Clinical assessment of pathological myoclonus requires a systematic approach. On neurological examination, it is important to note if the myoclonus appears at rest, on posture or during action. If present at rest, a spinal or brainstem source is more likely, whereas, if action induced, a cortical source should be suspected. Distribution is also important: cortical myoclonus is typically focal or multifocal, spinal segmental myoclonus can also be focal (but usually is stimulus sensitive and not action induced), while generalised myoclonus is generally subcortical (brainstem or propriospinal). Generalised myoclonus …

El presente artículo constituye la sistematización de una experiencia formativa sobre metodologías implicativas de investigación social. En tal sentido, se podría interpretar como el relato de la experiencia vivida; un relato de los sentidos, un punto de vista de los múltiples sentidos que se hubiesen podido construir desde la experiencia del seminario-taller como apuesta pedagógica generadora de diálogo de saberes, saberes sobre eso que apasiona a todos los participantes en ese proceso de formación: la investigación implicada, articulada con los procesos de comunicación y cambio social.

Neospora caninum is a member of Apicomplexa phylum, the causative agent of neosporosis. The neosporosis combat is not well established and several strategies related to vaccine, chemotherapy and immune modulation are under development. In this work, we evaluated the effects of artemisinin (Art), methylene blue (MB) and pyrimethamine (Pyr) alone or associated, on N. caninum proliferation and elimination using LacZ tagged tachyzoites. The reactive oxygen species (ROS) production after incubation with Art were also performed. Our results indicate that combinations of classical antimalarial drugs improve the parasite control, allowing the use of three drugs in a single dose. Additionally, artemisinin demonstrated distinct ROS production patterns in intra and extracellular N. caninum forms. The drug repurposing appears as a suitable approach, allowing a fast and safe method to evaluate old drugs but novel candidates against neosporosis.

Aims: To evaluate ethical and semiotechnique skills gain with intensive semiotechnique course to graduate medical students. Methods: Semiotics course was drawn up to 64 students of four medical courses of Belem, Para, Brazil. The course took place in two stages: the first for 32 students starting the third semester of the medical course, and the second for 32 students that started the internship. The course was taught intensively in two weekends, with didactic material prepared by the researchers. Pre-and post-training assessment was performed for verification of ethical skills needed in the doctor-patient relationship and the practical knowledge and skill in the technical implementation of the physical examination. Results: The students of 2nd year, in the eight proposed stations, have an average gain of 85.84%, reaching individually in some stations an improvement up to 120% as "Precordium” and “painful maneuvers of the abdomen" stations. The students of the 5th year initial notes average was 6.06, evolving to 9.21, with average percentage of 54.42% gain. For matters of ethical principles in dealing with the patient was observed initial average 5.05 that after the course has evolved to 9.36 to students of 2nd year and 6.16 to 9.60 in fifth year. In the evaluation of performance in implementing the semiotechnique maneuvers were observed initial notes of 4.76 and 5.95 to 8.51 and 8.82 respectively for students of 2nd and 5th year. Conclusion: The intensive course implemented proved to be effective in semiotechnique skills gain, both in improving ethical attitudes in dealing with the patient, as well as on the playing technique of physical examination.

OBJECTIVE: The posterosuperior shoulder access used in surgical treatment for acromioclavicular dislocation was constructed through dissection of 20 shoulders from 10 recently chilled adult cadavers, and the distances from this route to the nearby neurovascular structures were analyzed. METHODS: A Kirschner wire was introduced into the top of the base of the coracoid process through the posterosuperior shoulder access, in the area of the origin of the conoid and trapezoid ligaments, thus reproducing the path for inserting two anchors for anatomical reconstruction of the coracoclavicular ligaments. The smallest distance from the insertion point of the Kirschner wire to the suprascapular nerve and artery/vein was measured. RESULTS: The mean distance from the suprascapular nerve to the origin of the coracoclavicular ligaments at the top of the base of the coracoid process was 18.10 mm (range: 13.77-22.80) in the right shoulder and 18.19 mm (range: 12.59-23.75) in the left shoulder. The mean distance from the suprascapular artery/vein to the origin of the coracoclavicular ligaments was 13.10 mm (range: 9.28-15.44) in the right shoulder and 14.11 mm (range: 8.83-18.89) in the left shoulder. Comparison between the contralateral sides did not show any statistical difference. CONCLUSION: The posterosuperior shoulder access route for anatomical reconstruction of the coracoclavicular ligaments in treating acromioclavicular dislocation should be performed respecting the minimum limit of 8.83 mm medially. RESUMO OBJETIVO: Os autores fizeram o acesso posterossuperior do ombro usado no tratamento cirúrgico da luxação acromioclavicular, a partir da dissecção de 20 ombros de 10 cadáveres adultos recém-resfriados, e analisaram as distâncias da via às estruturas neurovasculares próximas. MÉTODOS: Introduziu-se um fio de Kirschner no topo da base do processo coracoide pelo acesso posterossuperior do ombro, na área de origem dos ligamentos conoide e trapezoide, para reproduzir o trajeto da inserção de duas âncoras para reconstrução anatômica dos ligamentos coracoclaviculares. Mediu-se a menor distância do ponto de inserção do fio de Kirschner ao nervo e à artéria/veia supraescapular. RESULTADOS: A média da distância do nervo supraescapular até a origem dos ligamentos coracoclaviculares no topo da base do processo coracoide foi de 18,10 mm (13,77 a 22,80) no ombro direito e 18,19 mm (12,59 a 23,75) no ombro esquerdo. A média da distância da artéria/veia supraescapular até a origem dos ligamentos coracoclaviculares foi de 13,10 mm (09,28 a 15,44) no ombro direito e 14,11 mm (08,83 a 18,89) no ombro esquerdo. Não houve diferença estatística comparativa entre os lados contralaterais. CONCLUSÃO: A via de acesso posterossuperior do ombro para reconstrução anatômica dos ligamentos coracoclaviculares no tratamento das luxações acromioclaviculares deve ser feita com respeito ao limite de 08,83 mm medialmente.

Introdução: O Mini-Mental State Examination é o teste de rastreio de défice cognitivo/demência mais difundido. No nosso país têm-se utilizado pontuações de corte definidas por grupos de literacia, mas existem novas propostas sustentadas por estudos mais representativos. Propomo-nos confirmar a influência da idade e da escolaridade no desempenho, avaliar a capacidade discriminativa dos novos dados normativos e testar a acuidade diagnóstica das pontuações de corte validadas para o défice cognitivo ligeiro e para as formas mais prevalentes de demência. Material e Métodos: O estudo incluiu 1 441 participantes escolarizados, divididos em sete subgrupos: Défice cognitivo ligeiro, doença de Alzheimer, demência fronto-temporal, demência vascular, demência com corpos de Lewy, controlo-comunidade e controlo-clínica- memória.Resultados: Em conjunto, idade e escolaridade explicam 10,4% da variância dos resultados no Mini-Mental State Examination, com ambas contribuindo significativamente para a predição dos resultados. A acuidade diagnóstica com base nos dados normativos mais recentes foi sempre superior à conseguida com as pontuações de corte de validação, revelando uma especificidade excelente (superior a 90%) e uma sensibilidade também excelente para a doença de Alzheimer ligeira (91%), boa para demência com corpos de Lewy (78%), baixa para o défice cognitivo ligeiro (65%) e demência fronto-temporal e demência vascular (55%). Discussão e Conclusões: O desempenho no Mini-Mental State Examination é influenciado pela idade e pela escolaridade, apoiando a utilização de dados normativos que considerem estas variáveis. Com esta abordagem, o Mini-Mental State Examination poderá ser um instrumento sensível e específico para o rastreio da doença de Alzheimer em todos os níveis de cuidados de saúde, mas a acuidade de diagnóstico é limitada noutras situações frequentes em consultas especializadas, como o défice cognitivo ligeiro ou outras formas de demência.

To investigate the frequency, localizing significance, and intensity characteristics of ictal vocalization in different focal epilepsy syndromes.Up to four consecutive focal seizures were evaluated in 277 patients with lesional focal epilepsy, excluding isolated auras and subclinical EEG seizure patterns. Vocalization was considered to be present if observed in at least one of the analyzed seizures and not being of speech quality. Intensity features of ictal vocalization were analyzed in a subsample of 17 patients with temporal and 19 with extratemporal epilepsy syndrome.Ictal vocalization was observed in 37% of the patients (102/277) with similar frequency amongst different focal epilepsy syndromes. Localizing significance was found for its co-occurrence with ictal automatisms, which identified patients with temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative analysis of vocalization intensity allowed to distinguish seizures of frontal from temporal lobe origin based on the intensity range (p = 0.0003), intensity variation (p 0.0001), as well as the intensity increase rate at the beginning of the vocalization (p = 0.003), which were significantly higher in frontal lobe seizures. No significant difference was found for mean intensity and mean vocalization duration.Although ictal vocalization is similarly common in different focal epilepsies, it shows localizing significance when taken into account the co-occurring seizure semiology. It especially increases the localizing value of automatisms, predicting a temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative parameters of the intensity dynamic objectively distinguished frontal lobe seizures, establishing an observer independent tool for semiological seizure evaluation.

Annual influenza vaccination is recommended for healthcare workers to reduce risk to themselves, their patients, and their families.12 Discussing mandatory vaccination, McCartney mentions our recent study,34 which found that a 10% rise in vaccination rate was associated with a 10% fall in sickness absence, which she said “may reflect better organised trusts being …

The three devastating pandemics of plague that humanity faced in the Middle Ages had a great impact on the European population and endorsed the causing agent of plague, the gram-negative bacillus Y...

Background Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. Methods and findings MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10−5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10−4), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. Conclusions This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide., Using genetic instruments, Cosetta Minelli and colleagues probe the causal nature of associations between early puberty, late puberty, and late-onset asthma., Author summary Why was this study done? Worldwide there has been a shift towards earlier puberty over time, possibly due to changes in childhood lifestyle and levels of adiposity. Early puberty has been linked to an increased risk of asthma in women, but findings are inconsistent across studies, and little research has been done in men. There is some suggestion that late puberty might also increase the risk of asthma. Studies performed so far have some methodological limitations that make it difficult to distinguish true effects from spurious findings. What did the researchers do and find? We studied the effect of age at puberty on asthma in women and men using Mendelian randomisation, an approach that exploits genetic data to overcome some limitations of classical observational studies. From the UK Biobank study, we analysed data on approximately 240,000 women and approximately 190,000 men with available genetic data and self-reported information on asthma and age at puberty (menarche for women and voice breaking for men). We found that women and men with early puberty had an increased risk of asthma of 8% and 7%, respectively. We found no evidence of a detrimental effect of late puberty on asthma. What do these findings mean? These findings, together with suggestions of other detrimental effects of early puberty on health, emphasise the importance of evaluating the overall evidence on health effects of early puberty. The similarity of findings in females and males might be explained by common biological or psychological factors related to early puberty, but further research is needed to investigate this.

To evaluate the evolution of the functional results from CTA(®) hemiarthroplasty for surgically treating degenerative arthroplathy of the rotator cuff, with a mean follow-up of 5.4 years.Eighteen patients who underwent CTA(®) partial arthroplasty to treat degenerative arthroplathy of the rotator cuff between April 2007 and June 2009 were reevaluated, with minimum and mean follow-ups of 4.6 years and 5.4 years, respectively. Pre and postoperative parameters for functionality and patient satisfaction were used (functional scale of the University of California in Los Angeles, UCLA). All the patients underwent prior conservative treatment for 6 months and underwent surgical treatment because of the absence of satisfactory results. Patients were excluded if they presented any of the following: previous shoulder surgery; pseudoparalysis; insufficiency of the coracoacromial arch (type 2 B in Seebauer's classification); neurological lesions; or insufficiency of the deltoid muscle and the subscapularis muscle.With a mean follow-up of 5.4 years, 14 patients considered that they were satisfied with the surgery (78%); the mean range of joint motion for active elevation improved from 55.8° before the operation to 82.0° after the operation; the mean external rotation improved from 18.9° before the operation to 27.3° after the operation; and the mean medial rotation remained at the level of the third lumbar vertebra. The mean UCLA score after the mean follow-up of 5.4 years was 23.94 and this was an improvement in comparison with the preoperative mean and the mean 1 year after the operation.The functional results from CTA(®) hemiarthroplasty for treating rotator cuff arthroplasty in selected patients remained satisfactory after a mean follow-up of 5.4 years.Avaliar a evolução do resultado funcional da hemiartroplastia CTAForam reavaliados 18 pacientes submetidos à artroplastia parcial CTACom um seguimento médio de 5,4 anos, 14 pacientes se consideravam satisfeitos com a cirurgia (78%). A amplitude de movimento articular melhorou na elevação ativa média e variou de 55,8° no pré-operatório para 82° no pós-operatório. A rotação externa média melhorou de em média 18,9° no pré-operatório para 27,3° no pós-operatório. A média da rotação medial manteve-se no nível da terceira vértebra lombar. O escore UCLA médio, após seguimento médio de 5,4 anos, foi de 23,94 e melhorou em comparação com as médias pré-operatória e do primeiro ano pós-operatório.Os resultados funcionais da hemiartroplastia CTA

Molecular dynamics simulations were successfully performed to understand the absorption mechanism of antimicrobial peptides LL-37, CATH-2, and SMAP-29 in a lung surfactant model. The antimicrobial peptides quickly penetrate in the lung surfactant model in dozens or hundreds nanoseconds, but they electrostatically interact with the lipid polar heads during the simulation time of 2 μs. This electrostatic interaction should be the explanation for the inactivation of the antimicrobial peptides when co-administrated with lung surfactant. As they strongly interact with the lipid polar heads of the lung surfactant, there is no positive charge available on the antimicrobial peptide to attack the negatively charged bacteria membrane. In order to avoid the interaction of peptides with the lipid polar heads, sodium cholate was used to form nanoparticles which act as an absorption enhancer of all antimicrobial peptides used in this investigation. The nanoparticles of 150 molecules of sodium cholate with one peptide were inserted on the top of the lung surfactant model. The nanoparticles penetrated into the lung surfactant model, spreading the sodium cholate molecules around the lipid polar heads. The sodium cholate molecules seem to protect the peptides from the interaction with the lipid polar heads, leaving them free to be delivered to the water phase. The penetration of peptides alone or even the peptide nanoparticles with sodium cholate do not collapse the lung surfactant model, indicating to be a promisor drug delivery system to the lung. The implications of this finding are that antimicrobial peptides may only be co-administered with an absorption enhancer such as sodium cholate into lung surfactant in order to avoid inactivation of their antimicrobial activity.