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Introduction: The aesthetic rehabilitation of endodontically treated teeth depends on the degree of destruction of the crown, the tooth in question, the bone support, the type of prosthesis and the types of forces to which these teeth will be submitted. The indirect composite resins have improved physical and mechanical properties thanks to the incorporation of inorganic components and multifunctional monomers with a greater number of bonding points, making them capable of solving the problems in which ceramic restorations would be indicated. Objective: To present a clinical case report of an aesthetic rehabilitation of anterior teeth with indirect composite resin as a viable and less expensive treatment alternative. Case Report: Upon clinical examination, extensive and deficient restorations were observed in the upper anterior teeth. The proposed treatment plan aesthetic rehabilitation of dental elements with ceromeres. Conclusions: This treatment represented a viable and less expensive option that can be used both in situations of great dental destruction and in small dental absences, in substitution for ceramic restorations. Introducción: La rehabilitación estética de los dientes tratados endodónticamente depende del grado de destrucción de la corona, el diente en cuestión, el soporte óseo, el tipo de prótesis y los tipos de fuerzas a las que estos dientes serán sometidos. Las resinas compuestas indirectas tienen propiedades físicas y mecánicas mejoradas gracias a la incorporación de componentes inorgánicos y monómeros multifuncionales con mayor número de puntos de unión, lo que las hace capaces de resolver los problemas en los que estarían indicadas las restauraciones cerámicas. Objetivo: Presentar un caso clínico de rehabilitación estética de dientes anteriores con resina compuesta indirecta como alternativa de tratamiento viable y menos costosa. Reporte de Caso: En el examen clínico, se observaron restauraciones extensas y deficientes en los dientes anteriores superiores. El plan de tratamiento propuesto para la rehabilitación estética de elementos dentales con cerómeros. Conclusiones: Este tratamiento representó una opción viable y menos costosa que se puede utilizar tanto en situaciones de gran destrucción dentaria como en pequeñas ausencias dentales, en sustitución de las restauraciones cerámicas. Introdução: A reabilitação estética de dentes tratados endodonticamente depende do grau de destruição da coroa, do dente em questão, do suporte ósseo, do tipo de prótese e dos tipos de forças a que esses dentes serão submetidos. As resinas compostas indiretas apresentam propriedades físicas e mecânicas aprimoradas graças à incorporação de componentes inorgânicos e monômeros multifuncionais com maior número de pontos de união, tornando-os capazes de solucionar os problemas em que seriam indicadas restaurações cerâmicas. Objetivo: Apresentar um relato de caso clínico de uma reabilitação estética de dentes anteriores com resina composta indireta como alternativa de tratamento viável e de menor custo. Relato de Caso: Ao exame clínico foram observadas restaurações amplas e deficientes nos dentes anteriores superiores. O plano de tratamento proposto reabilitação estética dos elementos dentários com cerômeros. Conclusões: Este tratamento representou uma opção viável e de menor custo que pode ser utilizado tanto em situações de grande destruição dentária como em pequenas ausências dentárias, em substituição às restaurações de cerâmica.

Objective To assess difficulties in filling the International Consultation on Incontinence Questionnaire Bladder Diary (ICIQ-BD), determining the most troublesome items and patients’ characteristics (age, education level, and professional activity) related to these difficulties. Methods A text composed of a clinical history of a fictitious patient with Lower Urinary Tract Symptoms (LUTS) was designed. 95 healthy volunteers (49 females, 46 males, mean age 45.6 ± 17.3 years) were asked to fill in the ICIQ-BD according to the data from the fictitious clinical history. Filling errors were analyzed, and patients’ demographic characteristics tested as predictors. Results Bladder Sensation Score is the most problematic item of the ICIQ-BD, with only 38% of patients accurately filling this item. No association was found between total number of errors and age or education level, but participants working in less specialized professions had more difficulty in filling the BD (mean: 7.00 vs 3.94 errors, P= .002). Conclusion ICIQ-BD is a reliable tool to assess for LUTS, but filling the Bladder Sensation Score item was more likely to be incorrectly filled by manual workers and volunteers with less intellectually demanding current professions.

Food allergies are usually managed by food avoidance. Hidden allergens in food, due to cross-contamination and/or allergenic additives added during production, place an important concern in today's increasing food allergy cases worldwide. Previous studies showed that the introduction of unacquainted food components, in an inflamed intestine, results in sensitization to this food. Thus, our aim was to evaluate the kinetics of multiple food allergy induction. Adult male C57BL/6 mice were divided into five groups, four of which were submitted to an intestinal inflammation induction protocol to peanuts. Egg white (OVA) diluted 1:5 v/v in distilled water was instilled by gavage 6h-before (PRIOR), concomitant (AT) and 6h-after (DURING) the onset of the peanut challenge diet. Positive control (POS CONT) and NEG CONT received saline per gavage. Finally, animals were challenged with subcutaneous injections of OVA. Results showed no changes in diet intake were observed. Anti-OVA polyisotypic IgG antibody titers significantly increased in AT. Flow cytometry revealed significant decrease in CD4+CD25+Foxp3+ and significant increase in TCD8+ in AT. Histomorphometrically, AT and DURING were classified as Infiltrative and Partial Destruction stages. PRIOR was classified as Infiltrative, while POS CONT was classified as Partial Destruction. NEG CONT was classified as Normal. Together, our results confirm that the introduction of unfamiliar food only a few hours before the initiation of a gut inflammation process is able to induce oral tolerance, however the introduction of a dietary protein concomitant to the onset or during an ongoing gut inflammation may induce multiple allergies.

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well-known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem (Para, Brazil) Health System. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of 40 mg prednisolone, 40 mg enoxaparin and macrolides (500 mg clarithromycin, 500 mg axetylcefuroxime) associated and followed in outpatient facilities. Two hundred and eight patients had an excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

Contains fulltext : 237261.pdf (Publisher’s version ) (Closed access) Adherence to national and international clinical practice guidelines is suboptimal throughout Europe. The European Association of Urology Guidelines Office project "IMAGINE" (IMpact Assessment of Guidelines Implementation and Education) has been developed to measure baseline adherence to urological guideline recommendations across Europe and to identify issues that drive nonadherence.

Objective: To assess the frequency of baked egg tolerance in IgE-mediated egg allergy patients through the oral food challenge and to assess the tolerance predictability of different skin prick tests, as well as specific serum IgE measurement to egg proteins. Methods: In this cross-sectional study, 42 patients with a diagnosis of egg allergy were submitted to different skin prick tests with egg (in natura, boiled, muffin, ovalbumin, and ovomucoid), and specific IgE to egg white, ovalbumin, and ovomucoid; as well as to the oral food challenge with food containing egg, extensively baked in a wheat matrix. Results: Of the total, 66.6% of patients tolerated the ingestion of egg-containing foods in the oral food challenge. A comparative analysis with positive and negative oral food challenge found no significant differences regarding age, gender, other food allergies, or even specific skin prick tests and IgE values between the groups. Conclusions: The study demonstrated an elevated frequency of baked egg food-tolerant individuals among egg allergy patients. None of the tested markers, skin prick tests, or specific IgE, were shown to be good predictors for identifying baked egg-tolerant patients. The oral food challenge with egg baked in a matrix is central to demonstrate tolerance and the early introduction of baked foods, improving patients’ and families’ quality of life and nutrient intake. Resumo: Objetivo: Avaliar a frequência de tolerância a alimentos assados com ovo em pacientes com alergia ao ovo mediada por IgE por meio do teste de provocação oral e verificar a capacidade de predição de tolerância ao ovo por meio de teste cutâneo de leitura imediata (Skin Prick Test ou SPT) e de dosagem sérica de IgE específica para componentes do ovo. Métodos: Estudo transversal, 42 pacientes com diagnóstico de alergia ao ovo foram submetidos a SPT com ovo (in natura, cozido, bolinho, ovoalbumina e ovomucoide), IgE específica para clara de ovo, ovoalbumina e ovomucoide e ao teste de provocação oral com alimento com ovo extensamente assado em matriz de trigo. Resultados: Dos pacientes, 66,6% toleraram a ingestão do alimento com ovo durante o teste de provocação oral. Não encontramos diferenças em relação a idade, gênero, outras alergias alimentares ou mesmo entre os valores dos SPT e IgE específicas na análise comparativa entre os grupos com teste de provocação oral positivo e teste de provocação oral negativo. Conclusões: Foi demonstrada uma elevada frequência de indivíduos tolerantes a ingestão de alimentos assados com ovo entre os pacientes com alergia a ovo mediada por IgE. Nenhum dos marcadores testados, SPT ou IgE específica, demonstrou ser bom preditor para identificar os pacientes tolerantes. Consideramos que os testes de provocação oral com alimentos com ovo assado sejam fundamentais para a introdução desses assados, melhorar a qualidade de vida e a ingestão de nutrientes dos pacientes e famílias.

AIMS Local anesthesia protocols for intradetrusor onabotulinum toxin A (BoNTA) injection lack standardization. We aimed to determine if an alkalinized lidocaine solution is more effective than lidocaine only. METHODS Patients of both genders aged 18 or above enlisted for intradetrusor BoNTA injection (idiopathic, neurogenic, and bladder pain syndrome) were included in a double-blinded randomized controlled trial after obtaining their informed consent. All participants filled a bladder diary and a urine culture was performed. Subjects were randomized 1:1 to Protocol A (20 ml 2% lidocaine + 10 ml 8.4% sodium bicarbonate) or Protocol B (20 ml 2% lidocaine + 10 ml 0.9% saline solution). A Numeric Rating Scale (0-10) was used to assess the level of pain immediately after the procedure (primary endpoint). Secondary endpoints included pain after 1 h, urinary tract infection, acute urinary retention, and hematuria related to the procedure. RESULTS A total of 116 patients were randomized. Baseline characteristics (age, sex, indication, and bladder diary parameters) of patients in Group A and B were similar. Pain scores at the end of the procedure were significantly lower with the alkalinized solution (Protocol A and B, respectively, 2.37 ± 0.31 vs. 4.44 ± 0.36, p

Aim Lower urinary tract symptoms (LUTS) are a common urological referral, which sometimes can have a neurological basis in a patient with no formally diagnosed neurological disease (“occult neurology”). Early identification and specialist input is needed to avoid bad LUTS outcomes, and to initiate suitable neurological management. Methods The International Continence Society (ICS) established a neurological working group to consider;1. Which neurological conditions may include LUTS as an early feature?2. What diagnostic evaluations should be undertaken in the LUTS clinic?A shortlist of conditions was drawn up by expert consensus and discussed at the annual congress of the International Neurourology Society. A multidisciplinary working group then generated recommendations for identifying clinical features and management. Results The relevant conditions are multiple sclerosis (MS), multiple system atrophy (MSA), normal pressure hydrocephalus (NPH), early dementia, Parkinsonian syndromes (including early Parkinson’s Disease and Multiple System Atrophy) and spinal cord disorders (including spina bifida occulta with tethered cord, and spinal stenosis). In LUTS clinics, the need is to identify additional atypical features; new onset severe LUTS (excluding infection), unusual aspects (e.g. enuresis without chronic retention) or “suspicious” symptoms (e.g. numbness, weakness, speech disturbance, gait disturbance, memory loss/ cognitive impairment, and autonomic symptoms). Where occult neurology is suspected, healthcare professionals need to undertake early appropriate referral; central nervous system (CNS) imaging booked from LUTS clinic is not recommended. Conclusions Occult neurology is an uncommon underlying cause of LUTS, but it is essential to intervene promptly if suspected, and to establish suitable management pathways.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical canc...

IntroductionAs a result of the coronavirus disease 2019 (COVID-19) pandemic the year 2020 brought major changes on the delivery of health care and face to face physician patient communication was significantly reduced and the practice of remote telehealth care using computer technology is assuming a standard of care, particularly, with COVID-19 patients with attempts to reduce viral spread.ObjectiveTo describe the clinical practice experience using telemedicine towards COVID-19 and the respective clinical outcomes.MethodsWe performed a pilot open-label non-randomized, controlled clinical trial. The patients were divided into four groups, according severity of symptoms: (1) asymptomatic, (2) mild symptoms, (3) moderate symptoms and (4) severe symptoms, and were followed up for five days, counted from the beginning of the symptoms. A drug intervention was performed in group 3, for which the protocol followed as suggested by the International Pulmonology Society’s consensus for adults with moderate symptoms: first day (attack phase) hydroxychloroquine sulfate 400 mg 12/12h; second to fifth day (maintenance phase) 200 mg (half pill) 12/12h. The medication was associated with azithromycin 500mg once a day for five days. For children with moderate symptoms were used: hydroxychloroquine sulfate 6.5 mg/kg/dose every 12 hours in the first day and 3.25 mg/kg/dose every 12 hours from day 2 to 5. The therapeutic response was telemonitored. Group 4 patients were directly oriented to seek hospital care. During the use of the drugs, the patients were telemonitored daily.ResultsOne hundred eighty-seven patients were seen with mean age of 37,6 years (±15,6). The most frequent symptom was cough (57,6%), followed by malaise (60,3%), fever (41,1%), headache (56,0%), muscle pain (51,1%). Of all the patients that sought telemedicine service in our center, 23% were asymptomatic despite contact with people with probable diagnostic of COVID-19; 29,4% reported mild symptoms, 43,9% moderate symptoms, and 3,7% severe symptoms. It was possible to observe in patients treated their symptoms of COVID-19 (group 3) with hydroxychloroquine and azithromycin for five days, presented statistically better improvement of the symptoms when compared to those that did not follow the protocol (p = 0.039). Three patients were hospitalized and discharged after recovery.ConclusionsOur study showed that patients with COVID-19 who had delivery of health care through telemedicine initiated in early stages of the disease presented satisfactory clinical response, reducing the need of face-to-face consultations and hospitalizations. Our results indicate that the use of telemedicine with diagnosis and drug treatment protocols is a safe and effective strategy to reduce overload of health services and the exposure of healthcare providers and the general population to infected patients in a pandemic situation.Trial registrationRBR-658khmHuman Research Ethics Committee number: 30246520.0.0000.0069

Computer vision is present in several areas of science, from the classification of people to the identification of cancer cells, which have become published in several publications. One of these applications is the identification of people's movements and gestures, including people with disabilities, for example. In this work, a technique called StarRGB is used in conjunction with a Convolutional Neural Network (CNN) for classifying the gait movements made by patients in a rehabilitation process. The StarRGB technique condenses temporal information from all images of a video into a single RGB image. Then, the obtained image is passed as input to a developed CNN so that it extracts the features of the image and classifies the movement performed in six classes. After the experiments, the results achieve a mean accuracy over the six classes of 99.64% and an AUC of 0.997, which shows the efficacy of this proposal to classify gaits using only ordinary RGB cameras.

The civil construction industry is one of the sectors that most consume natural resources in the world and, consequently, one of that generate more waste. Thinking about constructive techniques that generate less impact on the environment is vital to ensure sustainable development. In this scenario, the Life Cycle Assessment (LCA) has been presented as an internationally recognized approach, that assesses the potential impact of products and services on human health and the environment, throughout its entire life cycle. Aimed to identify construction techniques and vertical closing systems that generate less impact and consumption of natural resources, the impacts generated by the life cycle of the three vertical closing systems most applied in construction sites in Brazil were compared: ceramic brick masonry system (CBr); concrete block masonry system (CBk); and structural blocks masonry system (SBk). The SBk proved to be the least impacting to the “Resource Scarcity”, “Damage to Human Health”, and “Damage to the diversity of Ecosystems” interesting areas. This performance is directly related to the use of cement CPIII type and also by the fact that the SBk consumes less concrete and mortar than the others. Already the "Water Consumption" area, the CBk was the least impacting due to the lower consumption of electricity during its life cycle. The reliability of the results was proven through a sensitivity analysis of the normalization and characterization factors, which consisted of comparing the results obtained by applying two different methodologies. It is believed that the LCA study carried out can assist in the decision-making process regarding the choice of the most sustainable construction method.

This study applies bibliometric analysis to senior tourism research from 1998 to 2017, identifies its intellectual structure, emerging trends, and future research opportunities. Data collected from the Web-of-Science and Scopus is used to build an expanded network encompassing 700 core articles and 7221 citations. The results reveal a slowly increasing growth of research, with the last period including 41% of outputs. The most cited papers are mainly older, represent 1.99% of the sample and account for 8.52% of citations. The network of journals and institutions show the highest ranking to be in Tourism Management and in the University of Queensland. The identification of structural holes, critical articles and the keyword analysis highlights priorities in senior tourism, pointing to new opportunities for research. The dynamic analysis of the last two decades using CiteSpace for co-citation and co-occurrence network analysis aims to equip researchers and the hospitality industry with new exploration tools.

Background/aims Sacral neuromodulation (SNM) is a well-established treatment in several urinary and bowel dysfunctions, nevertheless its role on sexual dysfunction remains unclear. We evaluate the impact of SNM on sexual function and its association with age at SNM, functional diagnosis and post-void residual urine (PVR) before SNM. Methods Patients who had SNM were retrospectively analyzed. Sexual function was assessed before and after treatment with the International Index of Erectile Function (IIEF-5) for men and the Female Sexual Function Index (FSFI) for women. IIEF-5 and FSFI were also associated with age at SNM, functional diagnosis, and PVR. Results Fifteen females and 9 males, with a median age of 41 years (26-72 years), median follow-up 20.7 months (2-53 months) were enrolled. IIEF-5 improved in 4 patients (p = 0.06), and FSFI total score in 5 (p = 0.2). There was significant association between functional diagnosis and FSFI total score (p = 0.05), and FSFI specific domains of arousal (p = 0.03), lubrication (p = 0.04), and satisfaction (p = 0.03), with significant improvement showed in patients with detrusor overactivity with impaired contractility. Conclusion Although gains observed in IIEF-5 and FSFI were modest, our preliminary results show that SNM may have favorable impact on sexual function.

Serotonin and nitric oxide seem to be involved in Dengue virus infection. The aim of this study was to investigate if SNPs in serotonin and nitric oxide are associated with dengue severity. A retrospective case-control study was conducted, with groups of dengue fever (DF; n = 78) and dengue hemorrhagic fever patients (DHF; n = 49). Genotyping was performed using qPCR and PCR. The power of the sample size was calculated by G*power software. The heterozygous SL for 5-HTTLPR SNP was significantly correlated with protection against progression to DHF in the codominant SS/SL/LL (OR = 0.22, 95% CI = 0.06–0.81, p = 0.011) and overdominant models SL vs SS + LL (OR = 0.19, 95% CI = 0.06–0.65, p = 0.003). For the ENOS (rs1799983) SNP, the genotype GT was positively associated with protection for development of the clinical form in DHF compared to dengue fever (OR = 0.39, 95% CI = (0.13–1.14), p = 0.0058) in codominant GG/GT/TT and overdominant model GT vs GG + TT (OR = 0.35, 95% CI = (0.12–1.02), p = 0.04). To our knowledge, this is the first study to identify the association of the serotonin and nitric oxide SNPs with dengue severity.

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belém do Pará Health System, Brazil. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of prednisolone, enoxaparin and macrolides associated and followed in outpatient facilities. Two hundred and eight patients had excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

Background While public health strategies to contain the current coronavirus disease 2019 (COVID-19) pandemic are primarily focused on social distancing and isolation, emerging evidence suggest that in some regions social isolation failed to lead to further decrease in the number of COVID-19 deaths in the long run. This apparent paradox was particularly observed in the northern region of Brazil, in the state of Amazonas. We hypothesized that the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, leading to more transmissible and pathogenic variants, could explain the lack of further reductions in COVID-19 new cases and related deaths in some regions. Our objective is to determine if social isolation is associated with the emergence of new SARS-CoV-2 variants, particularly the P.1 lineage and E484K mutants, in Brazil and in the state of Amazonas. Materials and methods We assessed the prevailing SARS-CoV-2 genomes present in Brazil available on the GISAID (Global Initiative on Sharing All Influenza Data) database collected between June 1, 2020, and January 31, 2021. Data regarding demographics, lineage, and prevalence of P.1 lineage and E484K mutations were obtained. Social isolation was measured using the Social Isolation Index (SII), which quantifies the percentage of individuals that stayed within a distance of 450 meters from their homes on a given day, between February 1, 2020, and January 24, 2021. The number of daily COVID-19 deaths was obtained from the Brazilian Ministry of Health (OpenDataSUS, 2021) between March 12, 2020, and January 10, 2021. SII was correlated with the prevalence P.1 lineage and E484K mutations in the eight following weeks. All univariate associations were estimated using the Spearman Correlation Index. 3D surfaces were employed to reflect the relationship between time, social isolation, and prevalence of genomic variants simultaneously. Results A total of 773 and 77 samples were obtained in Brazil and in the Amazonas state, respectively. In the state of Amazonas, SII on a given week was positively, significantly, and moderately or strongly (r > 0.6) correlated with the prevalence of both P.1 lineage and other E484K variants in the six following weeks after the SII on a given week. Conversely, in overall Brazil, correlations between SII and P.1 lineage and E484K variants were weaker and shorter, or negative, respectively. When SII was below 40%, P.1 lineage or E484K variants were not detected in the following weeks. When SII was above 40%, apparently exponential positive correlations between SII and prevalence of both P.1 lineage and E484K variants were observed. Conclusion The results of this study indicate that SII above 40% is associated with the emergence of SARS-CoV-2 E484K variants and P.1 lineage in the state of Amazonas, which was not observed in overall Brazil.

Background Chronic pancreatitis is a progressive inflammation of the pancreas associated to fibrosis, pancreatic atrophy, calcifications, and chronic pain. Intractable pain is the main indication for surgical treatment. Surgical procedures are based in ductal decompression, ductal drainage, and resection. Aim Analyze the surgical management of patients with symptomatic calcified chronic pancreatitis. Methods From March 2009 and September 2019, 12 patients underwent surgical treatment due to chronic calcified pancreatitis. There were eleven male (91.7%) and one female (8.3%) and the mean age was 58.2 years (range 48–70 years). Regular alcohol ingestion was observed in all patients (100%). The main indication for surgery was pain control in ten patients (83.3%). Results The procedures included Partington-Rochelle (6 patients, 50.0%), Frey procedure (3 patients, 25.0 %), pancreatoduodenectomy (2 patients, 16.6%) and total pancreatectomy (1 patient, 8.3%). Four patients (33.3%) had postoperative complications. No Clavien-Dindo ≥ 3b complications and no 90-days mortality were recorded in this series. Postoperative exocrine dysfunction was observed in 4 patients (33.3%), and all of them received pancreatic enzyme supplement. Conclusions Surgical treatment is a safe and feasible choice with acceptable morbidity and no mortality for symptomatic patients with calcified chronic pancreatitis.

© 2021 Elsevier B.V. All rights reserved., Circulating tumor cells (CTCs) have a potential role as the missing renal cell carcinoma (RCC) biomarker. However, the available evidence is limited, and detection methods lack standardization, hindering clinical use. We performed a systematic review on CTC enrichment and detection methods, and its role as a biomarker in RCC. Full-text screening identified 54 studies. Reviewed studies showed wide heterogeneity, low evidence level, and high risk of bias. Various CTC detection platforms and molecular markers have been used, but none has proven to be superior. CTC detection and CTC count seem to correlate with staging and survival outcomes, although evidence is inconsistent. CTC research is still in an exploratory phase, particularly in RCC. Further studies are still necessary to achieve a standardization of techniques, molecular markers, CTC definitions, and terminology. This is essential to ascertain the role of CTCs as a biomarker and guide future liquid biopsy research in RCC.

Introduction A major barrier for successful therapeutic approaches for COVID-19 is the inability to diagnose COVID-19 during the viral replication stage, when drugs with potential antiviral activity could demonstrate efficacy and preclude progression to more severe stages. Reasons that hamper an earlier diagnosis of COVID-19 include the unspecific and mild symptoms during the first stage, the delay in the diagnosis and specific management caused by the requirement of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 for the diagnosis of COVID-19, and the insufficient sensitivity of the RT-PCR-SARS-CoV-2, converse to what is recommended for a screening test during an outbreak. More sensitive and earlier diagnostic tools for COVID-19 should be unraveled as a key strategy for a breakthrough change in the disease course and response to specific therapies, particularly those that target the blockage of viral shedding. We aimed to create an accurate, sensitive, easy-to-perform, and intuitive clinical scoring for the diagnosis of COVID-19 without the need for an RT-PCR-SARS-CoV-2 (termed The AndroCoV Clinical Scoring for COVID-19 Diagnosis), resulting from a 1,757 population cohort, to eventually encourage the management of patients with a high pre-clinical likelihood of presenting COVID-19, independent of an RT-PCR-SARS-COV-2 test, to avoid delays and loss of appropriate timing for potential therapies. Methods This is a post-hoc analysis of clinical data prospectively collected of the Pre-AndroCoV and AndroCov Trials, which resulted in scorings for the clinical diagnosis of COVID-19 based on the likelihood of presenting with actual COVID-19 according to the number of symptoms, presence of anosmia, and known positive household contact. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and accuracy were calculated for subjects screened in two different periods and both periods together, for females, males, and both, in a total of nine different scenarios, according to combinations of one, two, or three or more symptoms or the presence of anosmia in subjects without known positive household contacts, and no symptoms, one, two, or three or more symptoms, or presence of anosmia or ageusia in subjects with known positive household contacts. Scorings that yielded the highest pre-test probability, sensitivity, and accuracy were selected. Results Of the 1,757 patients screened, 1,284 were diagnosed with COVID-19. The scoring that required: (1) two or more symptoms, or anosmia or ageusia alone, for subjects without known contact; or (2) one or more symptoms, including anosmia or ageusia alone, when with known positive contacts presented the highest accuracy (80.4%) among all combinations attempted, and higher sensitivity (85.7%) than RT-PCR-SARS-CoV-2 commercially available kit tests. Conclusion The AndroCoV clinical scoring for COVID-19 diagnosis was demonstrated to be a feasible, easy, costless, and sensitive diagnostic tool for the clinical diagnosis of COVID-19. Because the clinical diagnosis of COVID-19 avoids delays in specific treatments, particularly for high-risk populations, prevents false-negative diagnosis, and reduces diagnostic costs, this diagnostic tool should be considered as an option for COVID-19 diagnosis, at least while SARS-CoV-2 is the prevailing circulating virus and vaccination rate is below the required for herd immunity.

Food security is one of the biggest concerns in food processing. In recent decades, the effects of contaminants in food crops are currently compromising food security and human health. Food contamination can be microbiological, chemical and physical. It can occur on different steps of food processing, such as transport, storage and packaging of raw or processed food, as well as during heating processes. Therefore, substances including the additives can help to maintain the food security during food processing until it reaches the consumers. They can provide food preservation, maintaining freshness and preventing bacterial contamination, among many others. The additives from natural sources have been receiving more attention from food manufacturers when compared to the synthetic ones, due to their higher quality and safety. An example of natural additives are biosurfactants, which are derived from microorganisms. Interests in the use of biosurfactants have been increasing in the food market, as a result of their capacity to replace synthetic additives in the food industry. The objective of this chapter is to present the main microbial biosurfactants used to avoid contamination during food processing. We briefly discuss their potential applications as food preservatives, presenting antimicrobial, antioxidant and antibiofilm activities against food pathogens.

Context. The large-scale use of microservices and their increasing adoption in the industry in recent years has motivated researches on the most diverse aspects related to microservice-based development. However, as it is a relatively new topic, there is still no consolidated body of knowledge in the area. Objective. The present work intends to investigate the current state of research on microservices based on the formulation of six research questions covering fundamental aspects, such as: main interest topics and adopted standards, techniques and tools have been used and application areas. Method. From four digital libraries, 22 secondary studies were selected as a data source, which were analyzed and synthesized in the present study following the proposed research protocol. Results. Among the main topics of interest addressed, we highlight researches related to the applicability of microservice architecture, both by industry and academia. Results indicated that standards focus on challenges related to communication have been the most commonly considered by researchers of the area. Finally, the predominance in the use of the Docker container and the presence of DevOps practices in the automation of operations are noteworthy. Conclusions. The present mapping study points to some directions of research based on the identified gaps, such as modeling and testing of microservice applications, and addressing security aspects. Another promising point to be explored involves the combined use of microservice architecture with other related concepts such as IoT, smart cities, FOG computing and reactive systems, in order to reinforce the use of microservices, as well as creating new solutions and challenges to be researched.

BACKGROUND: Food allergies are usually managed by food avoidance. Hidden allergens in food, due to cross-contamination and/or allergenic additives added during production, place an important concern in today’s increasing food allergy cases worldwide. Previous studies showed that introduction of new food components, in an inflamed intestine, results in sensitization to this food. Thus, our aim was to evaluate the kinetics of multiple food allergy induction. METHODS: Adult male C57BL/6 mice were divided into five groups, four of which were submitted to an intestinal inflammation induction protocol to peanuts. Egg white (OVA) diluted 1:5 v/v in distilled water was instilled by gavage 6h-before (EXP-1), concomitant (EXP-2) and 6h-after (EXP-3) the onset of the peanut challenge diet. Positive control (POS CONT) and NEG CONT received saline per gavage. Finally, animals were challenged with subcutaneous injections of OVA. RESULTS: No changes in diet intake were observed. Anti-OVA total IgG antibody titers significantly increased in EXP-2. Flow cytometry revealed significant decrease in CD4+CD25+Foxp3+ and significant increase in TCD8+ in EXP-2. Histomorphometrically, EXP-2 and EXP-3 were classified as Infiltrative and Partial Destruction stages. EXP-1 was classified as Infiltrative, while POS CONT was classified as Partial Destruction. NEG CONT was classified as Normal. CONCLUSION: The introduction of a new food only a few hours before the initiation of a gut inflammation is able to induce oral tolerance, however the introduction of a new dietary protein concomitant to the onset or during an ongoing gut inflammation may induce multiple allergies.

Background Evidences suggest that alterations in circadian rhythms trigger the development of mental disorders. Eveningness, sleep behavior, and circadian genes polymorphisms have been associated with depression and anxiety symptomatology. However, the mechanism underlying these interactions is not well understood. We investigated the contribution of diurnal preference, sleep habits, and PER3 VNTR polymorphism (rs57875989) to depression and anxiety symptoms in a Northeast sample from the Brazilian population. Methods Eight hundred and four young adults completed the Morningness-Eveningness (MEQ), Munich Chronotype (MCTQ), Center for Epidemiologic Studies – Depression (CES-D), and Beck Anxiety Inventory (BAI) questionnaires. All participants were genotyped and linear regression was performed to test the interactions between the genetic /behavioral variants and depression/ anxiety symptoms. Results Eveningness and sleep behaviors (bedtime, wake-up time, sleep duration, and midpoint of sleep) were correlated with depression symptomatology, specifically in somatic factors of the CES-D questionnaire. No correlation was found between diurnal preference/sleep habits with anxiety symptoms for both BAI total score and its factors. However, women with PER34/4 genotype showed less interpesonal affect in depression symptomatology and more anxiety symptoms in four factors of the BAI questionnaire. Limitations Mainly because this study was based on self-report questionnaires and was limited to undergraduate students aging 18 to 30 years old. Conclusion These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women.

Social media analysis is a powerful tool for tourism research that, at a relatively low cost, can be used to manage and process large datasets of comments, ratings, and shares from different online communities. However, the heterogeneous nature of unsolicited opinions, the complexity of natural language assessment, and differences in the characteristics of social-data sources hinder the accurate assessment of preferences. Likewise, the use of solicited data sources, such as direct polling, is typically resource-intensive, time-consuming, and geographically limited. We analyze a hybrid approach that combines active polling with passive social media analysis to rate tourist experience. To this end, we present a novel multiple criteria decision analysis model for preference-extraction from solicited and unsolicited data. The proposed approach can significantly reduce the number of polls required to accurately assess the preferences of a community, especially when surveying rural destinations, which are sparsely populated geographic areas situated outside cities and towns. info:eu-repo/semantics/publishedVersion

Objective The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Methods We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. Results We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient –3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. Conclusions Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

BACKGROUND Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.

This study aims to compare the diversity and relative abundance of insect families collected in organic and conventional tomato production systems located in Alagoas, Northeast Brazil (09°81'76"S and 36°59'42"W). In this region, the visible spectrum is quite broad with sunlight throughout the year. Between rows of tomato plants, we set up a system of colored traps colored blue, yellow, white, green, red, and transparent. The experiment was between September 2015 and January 2017. The experimental design was completely randomized with six experiments and with five replicates. The data collected were analyzed using the Scott-Knott test at 5% probability. Analysis of the various diversity indices was made using DivEs software. A total of 56,955 insects from 25 families were collected from the organic system, and 10,660 from 22 families in the conventional system. We observed that, in the conventional system, insect diversity and relative abundance (AR) were significantly greater than those of the organic system. The averages of the indices were as follows: For the organic system: Shannon-Wiener, 2.97; Simpson, 0.79; Simpson Dominance, 0.19; Margalef, 5.13; and Pielou, 2.27, respectively. For the conventional system, the indices were 3.49; 0.86; 0.12; 6.93; and 2.56; respectively. Several families of insect orders collected in the colored traps showed significant mean values for families of pollinator insects, predators, parasitoids, and pests. This may aid in decision making for the protection of plants and other agroecosystems. The collected insects did not differ significantly in terms of diversity of families. Colored traps may be exploited for pest control and for conservation of insect. Key words: Vegetables, agricultural management, agroecology, plant protection.

Introduction: Transobturator tape (TOT) surgery has been associated with increased overactive bladder (OAB) although much controversy exists. Methods: In a cross-sectional study, women who underwent TOT surgery for pure stress incontinence (MonarcTM) answered the 6 questions of the symptom bother (SB) subscale of the OAB questionnaire – short form (OABq-SF) and an additional question regarding whether symptoms began after surgery. Women with SB score over the 4th quartile (≥30/100) were reassessed after a longer follow-up. Patients from primary care were recruited as controls. Results: We recruited 213 patients (135 in the TOT group and 78 age-adjusted controls). The mean age of operated patients was 58.7 ± 10.1 years with a mean follow-up of 25.9 ± 13.2 months. OABq-SF SB scores did not differ between the TOT group and controls (respectively, 18.5 ± 30 and 15.5 ± 6.7, p = 0.202). A total of 48% patients reported no relationship between symptoms and surgery. Highly symptomatic operated patients were reassessed after a longer follow-up (46.3 ± 10.6 months). The mean score in the second follow-up (n = 25) was not statistically different from the first assessment (46.4 ± 22.7 and 58.1 ± 19.8, p = 0.059). Conclusions: Women who underwent TOT surgery did not show increased OAB SB scores when compared to controls. Our study suggests that OAB symptoms may thus be present but overlooked during initial clinical assessment.

Due to the introduction of new M2M (Machine-to-Machine) functionalities and applications in the industry, new devices will need to be connected to existing communication networks, coexisting with current ones. The new mobile communication technologies, which are still in the standardization process, promise to comply with the communication requirements demanded by industrial automation systems. Therefore, this article has as main contribution to propose the development of a scheduling algorithm for devices (sensors and actuators) that use periodic network resources. This algorithm will aim to reduce network signaling, increase data transmission capacity, or increase the number of devices operating in the industrial network.

Part 1: Full Papers; International audience; Preventing falls is extremely important today as people live long sedentary lives. Fall prevention platforms can help, by stimulating seniors to perform exercises that improve balance and muscular strength. However, existing platforms for fall prevention mostly target individual users exercising at home. This paper describes the design and evaluation of a multi-player fall prevention game platform, FallSensing Games, to be used in senior care centers. The game design was inspired by the Otago Exercise Programme and the evaluation focused on biomechanical parameters, game experience, and technology acceptance. Results showed that the game was easy to follow, that seniors performed exercises correctly, and that the game integrated well with the activities of the senior care centers. Lessons learned from this project may inspire the development of similar platforms, and, in this way, support group exercise practices at senior care centers.

Polymorphisms in the cytokine genes have been associated with immunological variations that lead to susceptibility to HPV infection and the development of cervical cancer. This study aims to evaluate the influence of TNF-α -308G>A and IL-10 -819C>T polymorphisms on cervical cancer susceptibility through a case-control study, meta-analysis and Trial Sequential Analysis (TSA). A case–control study including 45 cervical cancer patients and 179 healthy controls was conducted. TNF-α -308G>A and IL-10 -819C>T polymorphisms were analysed using real-time polymerase chain reaction (PCR real-time). For the meta-analysis, published articles were electronically searched through the databases PubMed, Science Direct, Scopus and Web of science. In the case-control study, the IL-10 -819T carriers were associated with an increased risk of cervical cancer. While the TNF-α -308G>A polymorphism was not associated with cervical cancer, but sample power was less than 80% (70%). The meta-analysis and TSA showed that both TNF-α -308A (Overall, Asian, Caucasian and African analysis) and IL-10 -819T (Overall and Asian analysis) carriers were associated with an increased risk of cervical cancer. In conclusion, the IL-10 -819C>T and TNF-α -308G>A polymorphisms may be an important genetic biomarker for identifying the risk of developing cervical cancer.

In this paper, we propose a branch-and-price approach for solving the problem of maximizing the expected number of transplants in Kidney Exchange Programs (KEPs). In these programs, the decision on which transplants will be conducted is usually made with the support of optimization models with the assumption that all operations will take place. However, after a plan of transplants is defined, a pair may leave the KEP or a more accurate compatibility evaluation exam may invalidate a transplant. To model these possible events we consider probabilities of failure of vertices and of arcs and the objective of maximizing the expected number of transplants. The proposed approach is based on the so-called cycle formulation, where decision variables are associated with cycles. Built on the concept of type of cycle a branch-and-price algorithm is conceived. One subproblem is defined for each type of cycle. We present computational results of the proposed branch-and-price algorithm and compare them with solving directly the cycle formulation (with a general purpose mixed integer programming solver—CPLEX) showing that the proposed approach is the only one suitable for larger instances., This work is financed by the ERDF—European Regional Development Fund through the Operational, Programme for Competitiveness and Internationalization—COMPETE 2020, Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project “mKEP—Models and optimization algorithms for multi-country kidney exchange programs” (POCI-01-0145-FEDER-016677), is also financed by COMPETE: POCI-01-0145-FEDER-007043 and FCT within the Project Scope: UID/CEC/00319/2013 and FCT Project SFRH/BPD/101134/2014., info:eu-repo/semantics/publishedVersion

Oral mucositis (OM) is the most common debilitating complication among patients undergoing hematopoietic stem cell transplantation (HSCT). Photobiomodulation therapy (PBM) has shown beneficial effects in the treatment of OM, but few studies have evaluated its biological effects. This study evaluated the effect of PBM on the reduction of OM severity in patients undergoing HSCT and its relation to the modulation of the inflammatory response. Fifty-one patients were randomly assigned to two groups: PBM [submitted to PBM from admission (AD) to D+7] (n = 27) and control (n = 24) [received oral hygiene]. OM severity was assessed daily using the WHO scale. Saliva samples were collected on AD, D+7, and hospital discharge (HD) to measure CXCL8/interleukin 8, using cytometric bead array analysis and nitrite (NO) and myeloperoxidase (MPO) using colorimetric methods. PBM significantly reduced the severity of OM from D+7 to D+11 (p 0.05). All non-interventional patients (controls) who developed grade 2 or higher OM induced an increase of CXCL8 in saliva (n = 14) on D+7. PBM led to a decrease in CXCL8 on D+7 in 85% of patients, while 70.8% of patients in the control group presented an increase in this chemokine (p = 0.007). NO decreased from AD to D+7 in the PBM group (p 0.05). MPO significantly decreased on D+7 in both groups (p 0.05). PBM brought about a reduction in the severity of OM in patients undergoing HSCT, and this reduction was associated with a decrease in CXCL8 salivary levels.

The exploration of microbiomes has been posited as one of the pillars for innovative technologies to improve plant health and production. Agriculture is a promising area for this exploration as soils harbor vast and diverse microbial communities. A better understanding of the drivers influencing microbial biogeographical patterns is necessary to properly exploit this resource. Here, we aimed to describe biogeographical patterns of bacterial communities across a broad spatial scale by sampling soils in 10 distinct farms (a total of 285 soil samples) located at the most important region for sugarcane production in Brazil. Bacterial communities were analyzed in terms of community structure and composition and further correlated with soil characteristics, agricultural practices and geographical distances. Distance decay patterns were found either at the bacterial community level (as determined by T-RFLP and sequencing analyses) and at the distribution of most bacterial phyla. Partial redundancy analysis revealed that soil characteristics (i.e., pH, granulometry, potassium and phosphorus contents) and agricultural practices (i.e., amendments of vinasse, charcoal and mechanical harvesting) explained the differential structuring of bacterial communities to a higher extend than did geographical distance. The co-occurrence/mutual-exclusion analysis suggested a role of biological connections in these assemblages, such as the co-occurrence of Proteobacteria and Acidobacteria, both negatively correlated with Actinobacteria. Our data constitute the broadest assessment of biogeographical patterns of bacterial communities across agricultural soils. Collectively, it indicates that these bacterial assemblages are suitable for management, what support the development of microbiome-based strategies in agricultural settings.

Storage LUTS are highly influenced by behavioural traits, and correcting these is absolutely vital—all subsequent attempts at therapy may well fail if the basics are not properly addressed. The medications available are two main classes, the antimuscarinic drugs and a beta-3 adrenergic agonist. Antimuscarinics are well established and understood, but have significant side effects and limited efficacy which means most people stop taking them in a comparatively short time-frame. The beta-3 agonist is of comparable efficacy but generally has fewer side effects. Both drug classes have some specific contraindications. They can safely be used in combination for greater efficacy, and with no substantial increase in adverse effects. Refractory symptoms of overactive bladder may be treated with botulinum bladder injections if the patient has the aptitude and attitude to accept self-catheterization, which is needed in a minority. Sacral or tibial nerve stimulation are two established techniques which have rather differing profiles. For stress incontinence, surgical intervention is the main approach once conservative measures have properly been put in place. The operations for women are colposuspension, autologous sling and midurethral tape, but a major challenge is emerging for the latter as a result of problems from using mesh in vaginal surgery. For men, the interventions are artificial urinary sphincter or male sling. Major surgery is the only option if people still remain substantially symptomatic.

The tight regulation of lower urinary tract function by the central nervous system means that there is an extremely high likelihood of LUTS in neurological disease. The effect on the urinary tract is classified according to the location of the nervous deficit and can cause problems affecting muscle contraction (lower spinal lesions), co-ordination (upper spinal) and context (brain). Assessment needs to be detailed, covering the LUTS and other factors, along with weighing up general medical issues. Treatment aims to minimise risk of serious consequences, as well as ameliorating symptoms. Some of the most pertinent neurological conditions are stroke, MS, Parkinson’s disease and dementia.

The complexity of LUTS is greater when viewed in some of the contexts with which they are particularly associated. Mixed urinary incontinence reflects co-existence of both storage and voiding LUTS, each substantially affecting the patient’s quality of life. Pelvic organ prolapse (POP) is common and can cause voiding difficulty; furthermore, POP treatment can allow emergence of stress incontinence that was largely unrecognized before the operation. For men, erectile dysfunction (or concern about developing it) can affect treatment choice. LUTS are commonplace in metabolic syndrome, indicating how the complex physiology of the system is vulnerable to medical conditions. Urinary tract and sexually transmitted infections are exceptionally important factors complicating LUTS mechanisms and assessment. Prostatitis is an inflammation of the prostate which may be caused by infection or non-infectious causes, and is another cause of storage and voiding LUTS. The psychological impact of symptoms, assessment, and treatment are exceptionally influential in prognosis at every stage. Both adolescence and advanced age bring additional challenges.

This paper details the development and features of the CNN-corpus in Spanish, possibly the largest test corpus for single document extractive text summarization in the Spanish language. Its current version encompasses 1,117 well-written texts in Spanish, each of them has an abstractive and an extractive summary. The development methodology adopted allows good-quality qualitative and quantitative assessments of summarization strategies for tools developed in the Spanish language.

This paper details the features and the methodology adopted in the construction of the CNN-corpus, a test corpus for single document extractive text summarization of news articles. The current version of the CNN-corpus encompasses 3,000 texts in English, and each of them has an abstractive and an extractive summary. The corpus allows quantitative and qualitative assessments of extractive summarization strategies.

Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.

In logistics of home health care services in the Health Units, the managers and nurses need to carry out the schedule and the vehicles routes for the provision of care at the patients' homes. Currently, in Portugal, these services are increasingly used but the problem is still, usually, solved manually and without computational resources. The increased demand for home health care due to the boost of the elderly people number entails a high associated cost which, sometimes, does not guarantee the quality of the service. In this sense, the periodic vehicle routing problem is a generalization of the classical vehicle routing problem in which routes are determined for a time horizon of several days. In this work, it is provided a periodic vehicle routing problem applied in the Health Unit in Bragança. An integer linear programming formulation for the real database, allowed to solve the problem in an efficient and optimized way using the CPLEXR software., Programa Operacional Temático Factores de Competitividade(POCI-01-0145-FEDER-007043)

Supply chains have become one of the most important strategic themes in the aerospace industry in recent years as globalization and deep technological changes have altered the industry at many levels, creating new dynamics and strategies. In this setting, sustainability at the supply chain level is an emerging research topic, whose contributions aim to support businesses into the future. To do so the development of new products and the response to new industry requirements, while incorporating new materials appears as a path to follow, which require more resilient and agile supply chains, while guaranteeing their sustainability. Such supply chains will be better prepared for the future complex challenges and risks faced by the aerospace companies. Such challenges are addressed in this work, where an integrated framework is proposed to contribute to the resilience and sustainability of aerospace supply chains. Using different analysis methods, the framework addresses four important challenges in the context of aerospace supply chain sustainability: evolution and new trends, performance assessment, supplier selection, and supply chain design and planning., POFC - Programa Operacional Temático Factores de Competitividade(POCI-01-0145-FEDER-007043), This work has been supported by project MITP-TB/PFM/0005/2013 in the frame of MIT-Portugal program, by COMPETE: POCI-01-0145-FEDER-007043 and FCT - Fundação para a Ciência e a Tecnologia within the project UID/CEC/00319/2013.

Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

TPS497 Background: There is lack of high-quality and comprehensive data on advanced urothelial cancer in Latin America. Pathological and clinical outcomes information of this cancer can help the scientific community to understand the current standard of treatment and identify possible gaps for optimal care. Very few translational studies were performed in advanced urothelial cancer in developing countries describing the prevalence of key biomarkers for targeted agents and immunotherapy. Methods: LACOG 1518 is a large multi-institutional retrospective study that will collect information about sociodemographic data, treatment and outcome of patients diagnosed with recurrent/ metastatic urothelial cancer in Latin America between January 2016 and December 2019. Socio-demographic characteristics, clinical-pathological features, treatment patterns and outcomes will be extracted from medical charts. Tumor tissue will be collected for fibroblast growth factor receptor (FGFR) gene mutation or fusion test in a central laboratory. A biorepository will be built for future translational research including PD-L1 test and next generation sequencing. Primary endpoint consists on characterize demographic, socioeconomic factors, medical and oncological history of patients diagnosed with recurrent/metastatic urothelial cancer. This study aim to describe treatment sequence, duration, best response and progression time in each line of therapy as well as survival at 1 and 2 years. Translational research endpoints are biomarkers prevalence and association with treatment responses and outcomes.

Background Seasonal variations in suicides have been reported worldwide, however, there may be a different seasonal pattern in suicide attempts. The aim of this study was to perform a systematic review on seasonality of suicide attempts considering potential interfering variables, and a statistical analysis for seasonality with the collected data. Method Observational epidemiological studies about seasonality in suicide attempts were searched in PubMed, Web of Science, LILACS and Cochrane Library databases with terms attempted suicide, attempt and season. Monthly or seasonal data available were evaluated by rhythmic analysis softwares. Results Twenty-nine articles from 16 different countries were included in the final review. It was observed different patterns of seasonality, however, suicide attempts in spring and summer were the most frequent seasons reported. Eight studies indicated differences in sex and three in the method used for suicide attempts. Three articles did not find a seasonal pattern in suicide attempts. Cosinor analysis identified an overall pattern of seasonal variation with a suggested peak in spring, considering articles individually or grouped and independent of sex and method used. A restricted analysis with self-poisoning in hospital samples demonstrated the same profile. Limitations Grouping diverse populations and potential analytical bias due to lack of information are the main limitations. Conclusions The identification of a seasonal profile suggests the influence of an important environmental modulator that can reverberate to suicide prevention strategies. Further studies controlling interfering variables and investigating the biological substrate for this phenomenon would be helpful to confirm our conclusion.