Inhibition of Microbicidal Activity of Canine Macrophages DH82 Cell Line by Capsular Polysaccharides from Cryptococcus neoformans.

Cryptococcus neoformans is a lethal fungus that primarily affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, which are part of the first line of defense and important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse," taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal, or capsule total did not induce apoptosis in the DH82 macrophage cell line. However, it was possible to demonstrate that the phagocytic activity was decreased after treatment with polysaccharides. In addition, recovered yeasts from macrophages treated with polysaccharides after phagocytosis could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the mRNA expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR-γ expression. Furthermore, our data suggest that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.

Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to restrain kisspeptin (KISS1)-neuron pulsatility in the arcuate hypothalamic nucleus, while also exerting a surge-like effect on KISS1-neuron activity in the AVPV hypothalamic nucleus. However, a mechanistic basis for this region-specific effect has remained elusive. Our genomic analysis in female mice demonstrate that some processes, such as restraint of KISS1-neuron activity in the arcuate nucleus, may be explained by region-specific estrogen receptor alpha (ERα) DNA binding at gene regulatory regions. Furthermore, we find that the Kiss1-locus is uniquely regulated in these hypothalamic nuclei, and that the nuclear receptor co-repressor NR0B1 (DAX1) restrains its transcription specifically in the arcuate nucleus. These studies provide mechanistic insight into how ERα may control the KISS1-neuron, and Kiss1 gene expression, to couple gonadotropin release to the developmental stage of the oocyte.

MnO2-Ir Nanowires: Combining Ultrasmall Nanoparticle Sizes, O-Vacancies, and Low Noble-Metal Loading with Improved Activities towards the Oxygen Reduction Reaction.

Although clean energy generation utilizing the Oxygen Reduction Reaction (ORR) can be considered a promising strategy, this approach remains challenging by the dependence on high loadings of noble metals, mainly Platinum (Pt). Therefore, efforts have been directed to develop new and efficient electrocatalysts that could decrease the Pt content (e.g., by nanotechnology tools or alloying) or replace them completely in these systems. The present investigation shows that high catalytic activity can be reached towards the ORR by employing 1.8 ± 0.7 nm Ir nanoparticles (NPs) deposited onto MnO2 nanowires surface under low Ir loadings (1.2 wt.%). Interestingly, we observed that the MnO2-Ir nanohybrid presented high catalytic activity for the ORR close to commercial Pt/C (20.0 wt.% of Pt), indicating that it could obtain efficient performance using a simple synthetic procedure. The MnO2-Ir electrocatalyst also showed improved stability relative to commercial Pt/C, in which only a slight activity loss was observed after 50 reaction cycles. Considering our findings, the superior performance delivered by the MnO2-Ir nanohybrid may be related to (i) the significant concentration of reduced Mn3+ species, leading to increased concentration of oxygen vacancies at its surface; (ii) the presence of strong metal-support interactions (SMSI), in which the electronic effect between MnOx and Ir may enhance the ORR process; and (iii) the unique structure comprised by Ir ultrasmall sizes at the nanowire surface that enable the exposure of high energy surface/facets, high surface-to-volume ratios, and their uniform dispersion.

An Uncommon Presentation of Cryptococcal Meningoencephalitis.

Cryptococcal meningoencephalitis (CM) remains a common cause of central nervous system infections. Patients usually present with headache, fever, malaise, and altered mental status over several weeks. Signs are often absent, but they may include meningism, papilledema, cranial nerve palsies, and depressed level of consciousness. Individuals with CM can occasionally present with small vessel vasculitis causing cerebral lesions. The literature regarding patterns of cerebrovascular injury in CM is scarce. We describe a case of CM in which an unusual presentation was observed: transient focal neurological symptoms initially with absence of fever that led to a misleading primary diagnosis of transient ischemic attack. Since neurological symptoms may be a manifestation of a cryptococcal infection, it is necessary to have a high degree of suspicion for this pathology in the presence of focal neurological deficits, even in patients with vascular risk factors, requiring a thorough etiological investigation.

A Fatal Cause of Rapidly Progressive Heart Failure in a Middle-Aged Woman.

Primary cardiac neoplasms are rare, with 3/4 cases being benign. Most malignant neoplasms are sarcomas. Clinically, they present as pseudovalvular obstruction or remote embolism and rarely as a paraneoplastic syndrome. Median survival depends on complete resection rather than histologic type. We describe the case of a 65-year-old woman who presented to the hospital with a three-month history of asthenia, anorexia, weight loss, and progressive worsening of exertional dyspnea. Transthoracic echocardiogram showed a bulky mass in the auricles with significant transvalvular obstruction of the mitral valve. The CT scan showed a voluminous mass in the interauricular septum with the invasion of both atria and restriction of flow in both pulmonary veins. A transvenous biopsy was performed and histology revealed a primary intimal sarcoma. The patient was not eligible for surgery and was proposed for palliative chemotherapy, but she succumbed to her illness in less than two weeks. This report describes this rare and rapidly fatal disease and reviews the literature.

Cancer-Related Characteristics Associated With Invasive Mechanical Ventilation or In-Hospital Mortality in Patients With COVID-19 Admitted to ICU: A Cohort Multicenter Study.

BACKGROUND: Coexistence of cancer and COVID-19 is associated with worse outcomes. However, the studies on cancer-related characteristics associated with worse COVID-19 outcomes have shown controversial results. The objective of the study was to evaluate cancer-related characteristics associated with invasive mechanical ventilation use or in-hospital mortality in patients with COVID-19 admitted to intensive care unit (ICU). METHODS: We designed a cohort multicenter study including adults with active cancer admitted to ICU due to COVID-19. Seven cancer-related characteristics (cancer status, type of cancer, metastasis occurrence, recent chemotherapy, recent immunotherapy, lung tumor, and performance status) were introduced in a multilevel logistic regression model as first-level variables and hospital was introduced as second-level variable (random effect). Confounders were identified using directed acyclic graphs. RESULTS: We included 274 patients. Required to undergo invasive mechanical ventilation were 176 patients (64.2%) and none of the cancer-related characteristics were associated with mechanical ventilation use. Approximately 155 patients died in hospital (56.6%) and poor performance status, measured with the Eastern Cooperative Oncology Group (ECOG) score was associated with increased in-hospital mortality, with odds ratio = 3.54 (1.60-7.88, 95% CI) for ECOG =2 and odds ratio = 3.40 (1.60-7.22, 95% CI) for ECOG = 3 to 4. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with in-hospital mortality. CONCLUSIONS: In patients with active cancer and COVID-19 admitted to ICU, poor performance status was associated with in-hospital mortality but not with mechanical ventilation use. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with invasive mechanical ventilation use or in-hospital mortality.

Diagnóstico e manejo cirúrgico de cisto radicular em prémaxila: relato de caso / Diagnosis and surgical management of radicular cyst in premaxilla: a case report

Introdução: O cisto radicular é o cisto odontogênico mais comum, com uma prevalência aproximada de 60%. Esta lesão é geralmente observada por radiografias de rotina ou a partir de uma tumefação local, mas basicamente é assintomática, com crescimento lento e se encontra vinculada à um dente desvitalizado, possuindo predileção por indivíduos do sexo masculino com faixa etária se enquadrando entre a terceira e quarta décadas de vida. Seu tratamento pode ser cirúrgico ou não, variando de acordo com a dimensão e localização da lesão. Relato de caso: Paciente feminino, 66 anos, com presença de cisto radicular em região anterior de maxila, vinculada ao elemento dentário 22. A mesma foi submetida à enucleação cirúrgica associada à curetagem local para remoção e diagnóstico adequado da lesão, a partir da análise anatomopatológica do espécime. Considerações finais: Por ser uma patologia muito comum nos maxilares, é pertinente que o profissional conheça suas características essenciais para o correto diagnóstico, bem como os tratamentos mais adequados para cada paciente e que, apesar de somente a realização do tratamento endodôntico ser uma opção, a ausência da avaliação histológica da lesão restringe o correto diagnóstico desta patologia... (AU)

Introduction: Radicular cysts are the most common odontogenic cyst, with a prevalence of approximately 60%. This lesion is usually observed by routine radiographs or presence of local swelling, but it is basically asymptomatic, with slow growth and it is associated with the root apex of a nonvital tooth, with a predilection for male individuals with ages ranging between the third and fourth decades of life. Its treatment can be surgical or not, varying according to the size and location of the lesion. Case report: A 66 year old female, with the presence of a radicular cyst in the anterior region of the maxilla, associated to the dental element 22 was evaluated. She was underwent surgical enucleation associated with local curettage for removal and proper diagnosis of the lesion, based on the anatomopathological analysis of the specimen. Final considerations: As it is a very common pathology in the jaws, it is pertinent that the professional knows its essential characteristics for the correct diagnosis, as well as the most appropriate treatments for each patient and that, although only endodontic treatment is an option, the absence of histological evaluation of the lesion restricts the correct diagnosis of this pathology... (AU)

Manejo cirúrgico combinado de comunicação buco-sinusal e reconstrução de tábua óssea vestibular usando fibrina rica em plaquetas e leucócitos / Combined surgical management of oroantral communication and buccal bone plate reconstruction using leukocyte- and platelet-rich fibrin

Introdução: A comunicação buco-sinusal é tida como uma comunicação entre a cavidade bucal e o seio maxilar, cuja qual possui variadas etiologias, sendo a mais comum a extração de dentes posteriores superiores, pela proximidade de seus ápices radiculares com o assoalho do seio maxilar. O diagnóstico é obtido a partir da combinação de anamnese, exame físico e exames imaginológicos, podendo ser por meio de radiografias ou tomografia. Há diversas abordagens para o tratamento, incluindo o uso de membranas de Fibrina Rica em Plaqueta e Leucócitos para obstrução local da comunicação. O objetivo deste trabalho é relatar e discutir o emprego de membrana de Fibrina Rica em Plaqueta e Leucócitos para manejo de uma comunicação buco-sinusal associado à reconstrução de tábua óssea vestibular com Stick Bone. Relato de caso: Mulher, 61 anos, compareceu ao atendimento odontológico relatando incômodo na região do dente 16 e história de extração do mesmo há cerca de 8 meses. Ao exame intra-oral, observou-se a presença área hiperemiada no alvéolo da região da extração e, ao exame tomográfico, foi observada solução de continuidade no assoalho do seio maxilar, sugerindo comunicação buco-sinusal associado à perda de tábua óssea vestibular local. Considerações Finais: Portanto, o uso destas membranas são adequados para obstrução destas comunicações, sendo um plugue adequado devido às suas propriedades adesivas na área de perfuração, não estar vinculado a nenhuma reação imunológica, preparação fácil e rápida, altamente biocompatível, baixo custo, prevenção da profundidade do sulco vestibular e não apresentar nenhum risco de infecção... (AU)

Introduction: The oroantral communication is a communication between the oral cavity and the maxillary sinus, which has different etiologies, being the most common the extraction of upper posterior teeth, due to the proximity of their root apexes to the floor of the maxillary sinus. Diagnosis is obtained from a combination of anamnesis, physical examination and imaging exams, which may be through radiographs or tomography. There are several approaches to treatment, including the use of Leukocyte- and Platelet-RichFibrin membranes for local obstruction of communication. The aim of this work is to report and discuss the use of a Leukocyte- and Platelet-Rich Fibrin membrane for the management of oroantral communication associated with the reconstruction of the buccal bone plate with Stick Bone. Case report: A 61-year-old woman reported discomfort in the region of right maxillary first molar and a history of extraction of the same for about 8 months. The intraoral evaluation revealed the presence of a hyperemic area in the alveolus of the extraction region, and the tomographic examination revealed an oroantral communication associated with loss of local vestibular bone plate. Final considerations: Therefore, the use of these membranes are suitable for obstructing these communications, being a propper plug due to its adhesive properties in the perforation area, not being associated to any immunological reaction, easy and fast preparation, highly biocompatible, low cost, prevention of the depth of the vestibular sulcus and do not present any risk of infection... (AU)

Rheuma SPACE - Standard Practice Aiming Clinical Excellence: the first Portuguese Rheumatology Department evaluation.

The Portuguese Rheumatology Society (SPR) embraced quality as a major goal and launched, in early 2015, a program to aim for excellence in global clinical care: Rheuma SPACE - Standard Practice Aiming Clinical Excellence. Evaluating daily reality is the first step in a quality development timeline, ultimately contributing for health gains. Herein we describe the results of the evaluation of the quality indicators defined for this project and the improvement strategies identified. The Rheuma SPACE project included three phases: 1) establishing a set of quality indicators and an excellence quality model; 2) assessment of the current care at Rheumatology departments concerning the defined quality indicators in the scope of the excellence model; and 3) elaboration of global and customized reports for each participating Rheumatology department, resulting in the identification of improvement opportunities. Ten Rheumatology departments, countrywide, including larger and smaller institutions, were asked to participate in Rheuma SPACE. This resulted in an individual report for each department along with global benchmarking practices analysis. Furthermore, a list of improvement initiatives was developed. We concluded that departments lack physicians and need exclusively dedicated nurses. Time dedicated to research and audit activities should be specifically allocated. Internal contracting is well established, and professionals are committed to targets. Processes are still suboptimal, needing standardization of triage criteria, more frequent follow-up, as well as better medical records and multidisciplinary coverage. Regarding outcomes, patients are satisfied with the provided care and professionals with the working environment. However, department facilities for the former, and career related aspects, for the latter should improve. With this innovative study conducted in Portugal we expect to have enlightened tailored opportunities for improvement, ensure patient-focused practices and be able to define the indispensable quality requirements for excellence.

Effect of perioperative hypothermia on surgical site infection in abdominal surgery: A prospective cohort study.

AIM: To estimate the incidence rates of surgical site infection and identify the independent effect of perioperative hypothermia on the incidence of this type of infection in patients undergoing abdominal surgery. BACKGROUND: Around the world, surgical site infection is a frequent complication in surgical patients, mainly causing increased morbidity and mortality rates and health service costs. DESIGN: A prospective cohort study. METHODS: The 484 patients were recruited from a large private philanthropic hospital in the state of São Paulo, Brazil, from July 2016 to May 2017. Crude and adjusted models were constructed for the hypothermia indicators to assess the effect of this exposure on surgical site infection. RESULTS: The incidence rate of surgical site infection was 20.25% (n = 98). The attributable fraction to exposed to hypothermia was >40%. A greater probability of developing surgical site infection (relative risk = 1.89) was found for patients who experienced body temperatures <36.0°C (from entry time into the operating room until the end of the surgery) for more than five hypothermic episodes or longer than 75 min. CONCLUSION: Perioperative hypothermia was an independent risk factor for surgical site infection. SUMMARY STATEMENT: What is already known about this topic? Around the world, surgical site infection is a complication that leads to damage to the patient and increased costs for the health services. Despite recent advances in surgical techniques, surgical site infection remains one of the most frequent complications in abdominal surgery. Perioperative hypothermia can increase the incidence rates of surgical site infection. There is evidence that perioperative hypothermia is associated with surgical site infection in abdominal surgery, but most studies were conducted in developed countries using retrospective designs. What this paper adds? Perioperative hypothermia was identified as an independent risk factor for surgical site infection in patients undergoing abdominal surgery. The attributable fraction to the exposed indicated that, if the main exposure of interest (perioperative hypothermia) could be prevented during surgical anaesthetic procedures, more than 40% of surgical site infection cases would be avoided. The classification of the American Society of Anaesthesiologists was independently associated with the surgical site infection and presented a dose-response effect among its categories. Spinal anaesthesia served as an independent protective factor for surgical site infection. The implications of this paper: The health service managers need to be aware of potential cost-savings associated with perioperative hypothermia prevention as a measure to reduce the incidence of surgical site infection. During the perioperative period, health professionals need to implement effective measures to maintain patients' normothermia, promoting improved care and surgical patient safety. In this context, the nurse's role is fundamental. Future research projects using a prospective design and developed to address the reality of developing countries can contribute to the strengthening and consistency of the findings with a view to a global understanding of the surgical site infection problem.

Obesidade na infância e adolescência / Obesity in childhood and adolescence

A obesidade é uma doença crônica e multifatorial com sérias repercussões na saúde. O excesso de peso na infância aumenta o risco de obesidade na adolescência e na vida adulta. A obesidade é uma das principais causas de hipertensão arterial em crianças e adolescentes. No sexo feminino, os problemas ginecológicos relacionados com a obesidade incluem as desordens menstruais e a diminuição da fertilidade na adolescência e na vida adulta. O controle dessa patologia evita a sua evolução para formas crônicas e graves, que acarretaria novos transtornos e consequências para essas jovens. A mudança de hábitos alimentares e a realização de atividade física são a principal linha de tratamento. O tratamento medicamentoso é reservado para portadoras de obesidade grave que apresentam comorbidades associadas e que não respondem às mudanças do estilo de vida. (AU)

Obesity is a chronic and multifactorial disease with serious repercussions on health. Overweight in childhood increases the risk of obesity in adolescence and adulthood. Obesity is one of the main causes of high blood pressure in children and adolescents, among others. In women, gynecological problems related to obesity include menstrual disorders and decreased fertility in adolescence and adulthood. The control of this pathology prevents its evolution to chronic and severe forms that would cause new disorders and consequences for these young women. The main line of treatment is to change eating habits and encourage physical activity. Drug treatment is reserved for patients with severe obesity, who have associated comorbidities and who do not respond to changes in lifestyle.(AU)

Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study. / Características e desfechos em curto prazo de pacientes com câncer esofágico em admissões não planejadas a unidades de terapia intensiva: um estudo de coorte retrospectiva.

OBJECTIVE: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. METHODS: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. RESULTS: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. CONCLUSION: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.

DH82 Canine and RAW264.7 Murine Macrophage Cell Lines Display Distinct Activation Profiles Upon Interaction With Leishmania infantum and Leishmania amazonensis.

Leishmaniasis is an anthropozoonotic disease, and dogs are considered the main urban reservoir of the parasite. Macrophages, the target cells of Leishmania sp., play an important role during infection. Although dogs have a major importance in the epidemiology of the disease, the majority of the current knowledge about Leishmania-macrophage interaction comes from murine experimental models. To assess whether the canine macrophage strain DH82 is an accurate model for the study of Leishmania interaction, we compared its infection by two species of Leishmania (Leishmania infantum and L. amazonensis) with the murine macrophage cell line (RAW264.7). Our results demonstrated that L. amazonensis survival was around 40% at 24 h of infection inside both macrophage cell lines; however, a reduction of 4.3 times in L. amazonensis infection at 48 h post-infection in RAW 264.7 macrophages was observed. The survival index of L. infantum in DH82 canine macrophages was around 3 times higher than that in RAW264.7 murine cells at 24 and 48 h post-infection; however, at 48 h a reduction in both macrophages was observed. Surprisingly at 24 h post-infection, NO and ROS production by DH82 canine cells stimulated with LPS or menadione or during Leishmania infection was minor compared to murine RAW264.7. However, basal arginase activity was higher in DH82 cells when compared to murine RAW264.7 cells. Analysis of the cytokines showed that these macrophages present a different response profile. L. infantum induced IL-12, and L. amazonensis induced IL-10 in both cell lines. However, L. infantum and L. amazonensis also induced TGF-ß in RAW 264.7. CD86 and MHC expression showed that L. amazonensis modulated them in both cell lines. Conversely, the parasite load profile did not show significant difference between both macrophage cell lines after 48 h of infection, which suggests that other mechanisms of Leishmania control could be involved in DH82 cells.

Características e desfechos em curto prazo de pacientes com câncer esofágico em admissões não planejadas a unidades de terapia intensiva: um estudo de coorte retrospectiva / Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study

RESUMO Objetivo: Mostrar o quadro clínico e os desfechos de uma coorte de pacientes críticos com câncer esofágico. Métodos: Conduzimos um estudo multicêntrico retrospectivo que incluiu pacientes com câncer esofágico admitidos a unidades de terapia intensiva em razão de doença aguda entre setembro de 2009 e dezembro de 2017. Colhemos os dados demográficos e as características clínicas de todos os pacientes incluídos, assim como as medidas de suporte a órgãos e os desfechos no hospital. Realizamos uma análise de regressão logística para identificar os fatores associados de forma independente com mortalidade hospitalar. Resultados: Dentre os 226 pacientes incluídos no estudo, 131 (58,0%) faleceram antes de receber alta hospitalar. O carcinoma espinocelular foi mais frequente do que o adenocarcinoma, e 124 (54,9%) pacientes tinham câncer metastático. As principais razões para admissão foram sepse/choque séptico e insuficiência respiratória aguda. Uso de ventilação mecânica (RC = 6,18; IC95% 2,86 - 13,35) e doença metastática (RC = 7,10; IC95% 3,35 - 15,05) tiveram associação independente com mortalidade hospitalar. Conclusão: Nesta coorte de pacientes com câncer esofágico admitidos à unidades de terapia intensiva em razão de doença aguda, a taxa de mortalidade hospitalar foi muito elevada. A necessidade de utilizar ventilação mecânica invasiva e a presença de doença metastática foram fatores independentes de prognóstico e devem ser levados em conta nas discussões a respeito dos desfechos destes pacientes em curto prazo.

ABSTRACT Objective: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. Methods: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. Results: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. Conclusion: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.

Design-controlled synthesis of IrO2 sub-monolayers on Au nanoflowers: marrying plasmonic and electrocatalytic properties.

We develop herein plasmonic-catalytic Au-IrO2 nanostructures with a morphology optimized for efficient light harvesting and catalytic surface area; the nanoparticles have a nanoflower morphology, with closely spaced Au branches all partially covered by an ultrathin (1 nm) IrO2 shell. This nanoparticle architecture optimizes optical features due to the interactions of closely spaced plasmonic branches forming electromagnetic hot spots, and the ultra-thin IrO2 layer maximizes efficient use of this expensive catalyst. This concept was evaluated towards the enhancement of the electrocatalytic performances towards the oxygen evolution reaction (OER) as a model transformation. The OER can play a central role in meeting future energy demands but the performance of conventional electrocatalysts in this reaction is limited by the sluggish OER kinetics. We demonstrate an improvement of the OER performance for one of the most active OER catalysts, IrO2, by harvesting plasmonic effects from visible light illumination in multimetallic nanoparticles. We find that the OER activity for the Au-IrO2 nanoflowers can be improved under LSPR excitation, matching best properties reported in the literature. Our simulations and electrocatalytic data demonstrate that the enhancement in OER activities can be attributed to an electronic interaction between Au and IrO2 and to the activation of Ir-O bonds by LSPR excited hot holes, leading to a change in the reaction mechanism (rate-determinant step) under visible light illumination.

Effects of corticosterone within the hypothalamic arcuate nucleus on food intake and body weight in male rats.

OBJECTIVE: Obesity is a major cause of morbidity and mortality. Few weight-reducing medications are available, and these have limited efficacy. Cushing's Syndrome (caused by elevated glucocorticoid levels) and obesity have similar metabolic features. Though circulating glucocorticoid levels are not elevated in obesity, tissue-specific glucocorticoid levels have been implicated in the development of the metabolic phenotype of obesity. Tissue glucocorticoid levels are regulated by 11ß-hydroxysteroid dehydrogenase type1 (11ßHSD1), which increases the local concentration of active glucocorticoids by the production of corticosterone from 11-dehydrocorticosterone. 11ßHSD1 is expressed in the hypothalamic arcuate nucleus (ARC), a major weight and appetite-regulating centre, and therefore represents a target for novel anti-obesity therapeutic agents. Thus, we sought to investigate the effect of chronic alterations of ARC corticosterone levels (mediated by 11ßHSD1) on food intake and body weight in adult male rats. METHODS: Recombinant adeno-associated virus particles bearing sense 11ßHSD1 (rAAV-S11ßHSD1) and small interfering 11ßHSD1 (rAAV-si11ßHSD1), respectively, were stereotactically injected into the ARC (bilaterally) of adult male Wistar rats. rAAV-GFP was injected into control groups of male Wistar rats. Food intake and body weight were measured three times a week for 70 days. Terminal brain, plasma and intrascapular brown adipose tissue (iBAT) samples were taken for measurement of mRNA expression and hormone levels. RESULTS: Compared to controls, rAAV-S11ßHSD1 injection resulted in higher ARC corticosterone levels, hyperphagia and increased weight gain. Conversely, rAAV-si11ßHSD1 injection (compared to controls) resulted in lower ARC corticosterone levels, higher iBAT uncoupling protein-1 mRNA expression and less weight gain despite similar food intake. CONCLUSIONS: Therefore ARC corticosterone, regulated by 11ßHSD1, may play a role in food intake and body weight regulation. These data have important implications for the development of centrally-acting 11ßHSD1 inhibitors, which are currently being developed for the treatment of obesity, metabolic disorders, and other conditions.

Live Birth in Sex-Reversed XY Mice Lacking the Nuclear Receptor Dax1.

The nuclear hormone receptor Dax1 functions during development as a testes-determining gene. However, the phenotype of male mice lacking Dax1 is strain-dependent due to the background-specific abundance of male-determining Sry gene-transcripts. We hypothesised that inter-individual variation in Sry mRNA-abundance would result in a spectrum of phenotypes even within-strain. We found that while all XY C57BL/6J mice lacking Dax1 presented as phenotypic females, there was a marked inter-individual variability in measures of fertility. Indeed, we report rare occasions where sex-reversed mice had measures of fertility comparable to those in control females. On two occasions, these sex-reversed XY mice were able to give birth to live offspring following mating to stud-males. As such, this work documents within-strain variability in phenotypes of XY mice lacking Dax1, and reports for the first time a complete sex-reversal capable of achieving live birth in these mice.

Effect of perioperative hyperglycemia on surgical site infection in abdominal surgery: A prospective cohort study.

BACKGROUND: Surgical site infection (SSI) remains one of the most frequent complications in abdominal surgery, and hyperglycemia prevention is recommended as a measure to reduce this type of infection. The aims of this study were to estimate the incidence of SSI and to identify the effect of perioperative hyperglycemia on the incidence of this type of infection in patients undergoing abdominal surgery. METHODS: We enrolled 484 abdominal surgery patients ≥ 18 years of age, recruited between July 2016 and May 2017. Data were collected through structured interviews and patient assessments in the perioperative period and at the surgical outpatient clinic (30th day after surgery). Crude and adjusted models were built to identify the effect of hyperglycemia on SSI. RESULTS: The incidence rate of SSI was 20.25%. The attributable fraction for patients exposed to hyperglycemia was >60%. In the multivariable analysis, patients with hyperglycemia, at the end of the surgery and 12 hours later, were more likely to develop this type of infection (relative risk = 1.89 and 2.17, respectively). CONCLUSIONS: Perioperative hyperglycemia was identified as an independent risk factor for SSI. The evidence generated reinforces the importance of proper glycemic control management in the perioperative period for the prevention of SSI.

Human african trypanosomiasis: current standing and challenges

Human African trypanosomiasis (HAT) caused by the protozoan Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, and transmitted by the tsetse fly (genus Glossina), affects 36 Sub-Saharan African countries with considerable public health impact. Despite approximately 15,000 infected individuals and 70 million at risk, in recent years the World Health Organization has mentioned removal of HAT from the list of Neglected Tropical Diseases by 2020, due to the decrease in cases over the last two decades. When untreated, the disease presents high lethality rates and the available treatments are complicated to administer, highly toxic, and do not guarantee cure, especially in the advanced stages of the disease. Further, there is no prospect for vaccine development in the near future. The present review compiles information on the history of the clinical aspects of HAT, as well as its epidemiology, diagnosis, therapy, and prophylaxis, as well as updating information on the current panorama and perspectives regarding the disease.

Rheuma SPACE - Standard Practice Aiming Clinical Excellence: description of the methodological approach.

BACKGROUND: Quality of care is a key component of the right to health, and the route to equity and dignity. The aim of the project Rheuma SPACE - Standard Practice Aiming Clinical Excellence was to develop a set of quality indicators focused in rheumatoid arthritis care and apply them to rheumatology departments of the Portuguese National Health Service in order to benchmark the care for these patients. This article details the methodology that was applied. METHODOLOGY: This was a single country, three-phase project, each phase comprising multiple steps. The first step defined quality indicators and the excellence quality model to be used. It involved a literature search for international benchmarking of quality of care initiatives and indicators, followed by a pre-selection of an initial set of indicators. The set of indicators was latter on narrowed after an online Delphi round with all Portuguese rheumatologists and two consensus meetings involving the study task force. A set of 26 quality indicators was defined, within the three classic Donabedian dimensions of healthcare quality: Structure (9), Processes (11), and Outcomes (6). These indicators cover eleven domains of quality of care: personnel and organizational structure, training and research, facilities, equipment and information technology, budgeting and financial resources, access to care, clinical records, patient communication, multidisciplinary management, clinical outcomes, and patient and personnel satisfaction. Decision on quality and excellence thresholds for each of the 26 quality indicators was agreed upon a consensus meeting gathering principal investigators of the eight Rheumatology Departments that decided to participate, task force core set members and invited representatives of all Portuguese Departments/Units. Rheumatoid arthritis was the chosen disease model of the project based on the reliability of the outcomes to be measured in the context of this condition. The second step was the assessment of the participating Rheumatology Departments. During eighteen months, research teams applied the 26 quality indicators to their own Departments. The third step comprised data analysis and the elaboration of individual Rheumatology Department reports and of a global public report. RESULTS: Eight Departments, comprising 80 specialists, 20 residents and 30 nurses, covering 5.904.080 inhabitants, underwent quality evaluation. More than one thousand patients (1,325) and 113 health professionals' surveys were analysed, as well as data from 570 clinical records and 3,927 medical appointments on rheumatoid arthritis patients. DISCUSSION: 26 quality indicators were used for the first evaluation of Portuguese Rheumatology Departments, turning Rheuma SPACE into a pioneer project. Data analysis and benchmarking will be the subject of a further publication.