Experimental keratitis induced in rat by Acanthamoeba from distinct morphological groups/genotypes: a histological and immunohistochemical evaluation.

Species of the genus Acanthamoeba are free-living protozoans that occasionally act as parasites, causing a severe, progressive corneal infection termed Acanthamoeba keratitis (AK). The variable pathogenic potential among Acanthamoeba lineages has been shown by in vitro assays, but little is known about the behavior of different strains in animal models of AK. This work aimed to evaluate the infectivity of Acanthamoeba from distinct morphological groups and genotypes in a rat model of AK and apply an immunohistochemical technique for histological characterization of the lesions. Only a strain classified as group I/genotype T17, isolated from a soil source, caused ulcerated corneal lesions in two Wistar rats (n = 9) subjected to intrastromal inoculation. Two strains derived from AK human cases (group II/genotype T4 and group III/genotype T5) did not induce corneal lesions in the rats. A previous association of group II/genotype T4 trophozoites with lethally irradiated Escherichia coli did not influence the infectivity. A hyperimmune serum produced in Wistar rats was validated by an immunocytochemical technique using the three distinct strains and then applied for immunohistochemistry. The abundance of antigenic residues was observed in both corneas with keratitis, suggesting that the infectious process tended to resolve. Despite the low infection rate of the AK Wistar rat model, we produced an immunochemical tool with a potential diagnostic application. We also showed for the first time the ability of Acanthamoeba from T17 genotype to cause AK in experimental conditions.

Marine Sensors: Recent Advances and Challenges.

The ocean has a huge impact on our way of life; therefore, there is a need to monitor and protect its biodiversity [...].

Conhecimento dos acadêmicos dos cursos da saúde acerca de vacinação / Knowledge of health course academics about vaccination / Conocimiento de académicos en cursos de salud sobre vacunación

Objetivo: Analisar os fatores associados ao conhecimento de acadêmicos de enfermagem e medicina acerca da vacinação. Método: Trata-se de um estudo descritivo e analítico, transversal, realizado com os acadêmicos dos cursos de Enfermagem e Medicina de uma universidade pública. Os dados foram obtidos através de questionários com perguntas sobre as características demográficas, acadêmicas e relacionadas ao tema vacinação. Os dados foram trabalhados no programa estatístico Stata 16. Resultados: Participaram desta pesquisa 113 estudantes, sendo maioria dos entrevistados do sexo feminino, vinculados ao curso da Enfermagem, com predomínio de idade na faixa etária entre 18 a 23 anos, e que se encontrava no terceiro ano de curso. Foi apontado baixo conhecimento dos acadêmicos, destacando-se uma associação significativa com as variáveis faixa etária, curso acadêmico e anos cursados. Conclusão: É importante salientar o papel da universidade na formação dos profissionais de saúde, pois os mesmos carecem de conhecimento ao longo da formação acadêmica acerca do tema vacinação. (AU).

Objective: To analyze the factors associated with the knowledge of nursing and medical students about vaccination. Method: This is a descriptive and analytical, cross-sectional study carried out with nursing and medical students at a public university. Data were obtained through questionnaires with questions about demographic, academic and vaccination-related characteristics. Data were processed using the Stata 16 statistical program. Results: 113 students participated in this research, the majority of respondents being female, nursing students, with a predominance of age in the age group between 18 and 23 years old, and who were in the third year of course. Low knowledge of academics was pointed out, highlighting a significant association with the variables age group, academic course and years studied. Conclusion: It is important to emphasize the role of the university in the training of health professionals, as they lack knowledge throughout their academic training on the topic of vaccination. (AU).

Objetivo: Analizar los factores asociados al conocimiento de estudiantes de enfermería y medicina sobre vacunación. Método: Se trata de un estudio descriptivo y analítico, de corte transversal, realizado con estudiantes de enfermería y medicina de una universidad pública. Los datos se obtuvieron a través de cuestionarios con preguntas sobre características demográficas, académicas y vacunales. Los datos fueron procesados mediante el programa estadístico Stata 16. Resultados: Participaron de esta investigación 113 estudiantes, siendo la mayoría de los encuestados del sexo femenino, vinculados a la carrera de Enfermería, con predominio de la edad en el grupo etario entre 18 y 23 años, y que estaban en el tercer año, por supuesto. Se señaló bajo conocimiento académico, destacándose asociación significativa con las variables grupo etario, curso académico y años de estudio. Conclusión: Es importante resaltar el papel de la universidad en la formación de los profesionales de la salud, ya que estos carecen de conocimientos a lo largo de su formación académica sobre el tema de la vacunación. (AU).

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil.

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

Functional Characterization of the Cell Division Gene Cluster of the Wall-less Bacterium Mycoplasma genitalium.

It is well-established that FtsZ drives peptidoglycan synthesis at the division site in walled bacteria. However, the function and conservation of FtsZ in wall-less prokaryotes such as mycoplasmas are less clear. In the genome-reduced bacterium Mycoplasma genitalium, the cell division gene cluster is limited to four genes: mraZ, mraW, MG_223, and ftsZ. In a previous study, we demonstrated that ftsZ was dispensable for growth of M. genitalium under laboratory culture conditions. Herein, we show that the entire cell division gene cluster of M. genitalium is non-essential for growth in vitro. Our analyses indicate that loss of the mraZ gene alone is more detrimental for growth of M. genitalium than deletion of ftsZ or the entire cell division gene cluster. Transcriptional analysis revealed a marked upregulation of ftsZ in the mraZ mutant. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics confirmed the overexpression of FtsZ in MraZ-deprived cells. Of note, we found that ftsZ expression was upregulated in non-adherent cells of M. genitalium, which arise spontaneously at relatively high rates. Single cell analysis using fluorescent markers showed that FtsZ localization varied throughout the cell cycle of M. genitalium in a coordinated manner with the chromosome and the terminal organelle (TMO). In addition, our results indicate a possible role for the RNA methyltransferase MraW in the regulation of FtsZ expression at the post-transcriptional level. Altogether, this study provides an extensive characterization of the cell division gene cluster of M. genitalium and demonstrates the existence of regulatory elements controlling FtsZ expression at the temporal and spatial level in mycoplasmas.

Proteomic and Glyco(proteo)mic tools in the profiling of cardiac progenitors and pluripotent stem cell derived cardiomyocytes: Accelerating translation into therapy.

Research in stem cells paved the way to an enormous amount of knowledge, increasing expectations on cardio regenerative therapeutic approaches in clinic. While the first generation of clinical trials using cell-based therapies in the heart were performed with bone marrow and adipose tissue derived mesenchymal stem cells, second generation cell therapies moved towards the use of cardiac-committed cell populations, including cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes. Despite all these progresses, translating the aptitudes of R&D and pre-clinical data into effective clinical treatments is still highly challenging, partially due to the demanding regulatory and safety concerns but also because of the lack of knowledge on the regenerative mechanisms of action of these therapeutic products. Thus, the need of analytical methodologies that enable a complete characterization of such complex products and a deep understanding of their therapeutic effects, at the cell and molecular level, is imperative to overcome the hurdles of these advanced therapies. Omics technologies, such as proteomics and glyco(proteo)mics workflows based on state of the art mass-spectrometry, have prompted some major breakthroughs, providing novel data on cell biology and a detailed assessment of cell based-products applied in cardiac regeneration strategies. These advanced 'omics approaches, focused on the profiling of protein and glycan signatures are excelling the identification and characterization of cell populations under study, namely unveiling pluripotency and differentiation markers, as well as paracrine mechanisms and signaling cascades involved in cardiac repair. The leading knowledge generated is supporting a more rational therapy design and the rethinking of challenges in Advanced Therapy Medicinal Products development. Herein, we review the most recent methodologies used in the fields of proteomics, glycoproteomics and glycomics and discuss their impact on the study of cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes biology. How these discoveries will impact the speed up of novel therapies for cardiovascular diseases is also addressed.

Residual neuromuscular blockade and late neuromuscular blockade at the post-anesthetic recovery unit: prospective cohort study.

INTRODUCTION AND OBJECTIVES: The use of neuromuscular blockers during surgery represented a landmark for anesthesiology. However, their use can prompt residual Neuromuscular Blockade (RNMB) and objective monitoring of neuromuscular function is crucial to warrant the recovery of muscle strength. The present study aimed to estimate the incidence of RNMB and late Neuromuscular Blockade (LNMB) at the Post-Anesthetic Recovery Unit (PACU). METHOD: The study included 85 patients, 43 of which received cisatracurium and 42 of which, rocuronium. The depth of the Neuromuscular Blockade (NMB) was assessed by Train Of Four (TOF). NMB reversal was performed with the administration of neostigmine and atropine.RNMB was defined when a patient presented TOF below 90% at the PACU. RESULTS: RNMB at the PACU was diagnosed in 39.5% and 40.5% of the patients receiving cisatracurium and rocuronium, respectively (p = 1.0). LNMB at the PACU was found in 32.6% and 16.7% of the patients receiving cisatracurium and rocuronium, respectively (p = 0.131). CONCLUSIONS: The incidence ofRNMB remains significant despite the use of intermediate-acting neuromuscular blockers and reversal agents. There was no statistically significant difference in the incidence of RNMB or LNMB in patients receiving cisatracurium or rocuronium. The use of objective NMB monitoring is effective for the diagnosis of RNMB, as well as for treatment management.

Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer.

Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3ß oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.

Structure and mechanism of the Nap adhesion complex from the human pathogen Mycoplasma genitalium.

Mycoplasma genitalium is a human pathogen adhering to host target epithelial cells and causing urethritis, cervicitis and pelvic inflammatory disease. Essential for infectivity is a transmembrane adhesion complex called Nap comprising proteins P110 and P140. Here we report the crystal structure of P140 both alone and in complex with the N-terminal domain of P110. By cryo-electron microscopy (cryo-EM) and tomography (cryo-ET) we find closed and open Nap conformations, determined at 9.8 and 15 Å, respectively. Both crystal structures and the cryo-EM structure are found in a closed conformation, where the sialic acid binding site in P110 is occluded. By contrast, the cryo-ET structure shows an open conformation, where the binding site is accessible. Structural information, in combination with functional studies, suggests a mechanism for attachment and release of M. genitalium to and from the host cell receptor, in which Nap conformations alternate to sustain motility and guarantee infectivity.

Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and -independent regulatory pathways.

Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the hrl promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the fur mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the fur mutant by ICP-MS revealed an important role of Fur in nickel acquisition.

Leg length discrepancy in adolescent idiopathic scoliosis / Dismetria dos membros inferiores na escoliose idiopática do adolescente / Discrepancia de la longitud de las piernas en la escoliosis idiopática del adolescente

ABSTRACT Objective The objective of this study is to evaluate leg length discrepancy in adolescent idiopathic scoliosis. Methods A retrospective study of 80 subjects with adolescent idiopathic scoliosis (AIS) was conducted. The inclusion criteria were patients aged 10 to 18 years old with posteroanterior (PA) and lateral full-length radiographs. The exclusion criteria were patients subjected to surgery or orthotic treatment, those with other spinal disease, and those with poor quality x-rays. The parameters evaluated were: age, sex, Risser stage (RS), triradiate cartilage (TC), scoliotic curvatures, differentiated according to Lenke classification, sagittal (SB) and coronal balance (CB), and leg length discrepancy, which was assessed through the difference between the femoral heads (LLD) and through the assessment of pelvic obliquity (PO). Results The majority of patients with AIS demonstrated a mild LLD (<1 cm). The mean LLD was significantly different (p<0.01) between the scoliotic population with a main thoracolumbar curvature and those with a main lumbar curvature. When there was an LLD, it was the left limb that was shortened in most cases. The side of the longer lower limb had a direct influence on the CB (p=0.052). Conclusions This study demonstrates that in an AIS population with small LLD values, the extent of the shortening has a stronger impact on coronal balance and location than on the dimension of the main scoliotic curvature. These results demonstrate the importance of a more in-depth study on the effects of LLD <1 cm in the development of AIS and coronal imbalance. Level of evidence IV; Case Series.

RESUMO Objetivo O objetivo deste estudo é avaliar a discrepância no comprimento dos membros inferiores numa população com escoliose idiopática do adolescente. Métodos Foi realizado um estudo retrospetivo de 80 indivíduos com escoliose idiopática do adolescente (AIS). Os critérios de inclusão foram pacientes de 10 a 18 anos com radiografias coronais e sagitais extralongas, excluindo-se aqueles submetidos à cirurgia ou tratamento com coletes Milwaukee ou Boston, com outras doenças da coluna vertebral ou com exames que não cumpriam a qualidade radiográfica protocolada pelo Centro Hospitalar. Os parâmetros avaliados foram: idade, sexo, estadio de Risser (RS), cartilagem trirradiada (TC), curvaturas escolióticas diferenciadas segundo a classificação de Lenke, balanço sagital (SB), coronal (CB) e discrepância no comprimento dos membros inferiores, avaliado pelo desnível entre as cabeças femorais (LLD) e através da avaliação da obliquidade pélvica (PO). Resultados A maioria dos pacientes com AIS demonstrou LLD ligeira (<1 cm). A média de discrepância no comprimento dos membros inferiores foi significativamente diferente (p<0,01) entre a população escoliótica com uma curvatura toracolombar principal em relação àquela com uma curvatura lombar principal. Quando existe LLD, o membro esquerdo encontra-se encurtado na maioria dos casos e a discrepância dos membros inferiores influencia diretamente no balanço coronal (p=0,052). Conclusão A partir deste estudo, verificamos que, na população com AIS com pequenos valores de LLD, a magnitude do encurtamento tem um impacto de maior relevo no equilíbrio coronal e na localização do que na dimensão da curvatura escoliótica principal. Estes resultados levantam a importância de um estudo mais aprofundado sobre a importância da LLD <1 cm no desenvolvimento de AIS e no desequilíbrio coronal. Nível de evidência IV; Série de Casos.

RESUMEN Objetivos El objetivo de este estudio es evaluar la diferencia de la longitud de los miembros inferiores en la escoliosis idiopática del adolescente. Métodos Se realizó un estudio retrospectivo de 80 pacientes con escoliosis idiopática de adolescente (EIA). Los criterios de inclusión fueron los pacientes de 10 a 18 años con radiografías posteroanteriores (PA) y laterales de longitud completa. Los criterios de exclusión fueron los pacientes sometidos a cirugía o tratamiento ortopédico, aquellos con otra enfermedad de la columna y aquellos con radiografías de mala calidad. Los parámetros evaluados fueron: edad, sexo, estadio Risser (RS), cartílago trirradiado (CT), curvaturas escolióticas, diferenciadas según la clasificación de Lenke, balance sagital (BS) y coronal (BC) y discrepancia en la longitud de la pierna (DLP), que se evaluó a través de la diferencia entre las cabezas femorales y mediante la evaluación de la oblicuidad pélvica (OP). Resultados La mayoría de los pacientes con EIA demostró DLP leve (< 1 cm). La media de la DLP fue significativamente distinta (p < 0,01) entre la población escoliótica con una curvatura toracolumbar principal y los pacientes con curvatura lumbar principal. Cuando había DLP, la extremidad izquierda se acortaba en la mayoría de los casos. El lado de la extremidad más larga tuvo influencia directa en el BC (p = 0,052). Conclusiones Este estudio demuestra que en una población con EIA y bajos valores de DLP, la extensión del acortamiento tiene impacto mayor en el balance y la ubicación coronal que en la dimensión de la curvatura escoliótica principal. Estos resultados muestran la importancia de un estudio más profundo sobre los efectos de DLP < 1 cm en el desarrollo de EIA y el desequilibrio coronal. Nivel de evidencia - IV; Serie de Casos.

Fatores associados ao uso do álcool entre homens autores de violência por parceiro íntimo no Ceará / Factors associated to the use of alcohol and the perpetration of physical violence between men authors of violence of intimate partner in the state of Ceará

Objetivo: analisar os fatores associados ao uso de álcool entre homens autores de violência por parceiro íntimo (VPI) no estado do Ceará. Métodos: estudo transversal-exploratório, com 152 homens em privação de liberdade por prática de VPI, sob custódia do Estado na Casa de Privação Provisória de Liberdade II. Dados coletados por questionário com quatro blocos: sócio demográfico, impulsividade (Barratt Impulsiveness Scale), uso abusivo de álcool e outras drogas (Alcohol, Smoking and Substance Involvement Screening Test) e histórico de violência. Os participantes foram categorizados em 0-10 para baixo risco; 11- 26 para risco moderado e > 27 para alto risco. Para análise, foi feita a correção de população finita. As associações em tabelas de contingência foram realizadas por meio do qui-quadrado de Pearson, cálculo da odds ratio e regressão logística com múltiplas variáveis independentes pelo IBM SPSS STATISTICS® 23.1. Resultados: a prevalência do uso de risco de álcool foi de XX%. Os fatores associados ao consumo de risco de álcool foram zona de nascimento (OR=6,52, P<0,001), uso de risco de tabaco (OR=7,94, P<0,001), autoafirmação de ciúmes (OR=2,66, P=0,017) e já ter sido casado/amasiado (OR=2,64, P<0,001). Conclusões: há elevada prevalência do uso de álcool entre os homens que perpetram VPI, tornando-se necessário o desenvolvimento de novos estudos e a criação de políticas públicas que influenciem na redução do consumo de álcool.

Supraclavicular nerve and superior trunk block for surgical treatment of clavicle fracture in a patient with Steinert's disease - Case report / Bloqueio do nervo supraclavicular e do tronco superior para tratamento cirúrgico de fratura de clavícula em paciente portador de doença de Steinert - Relato de caso

Abstract Background and objectives: Ultrasound-guided upper limb blocks may provide great benefits to patients with serious diseases. Patients with Steinert's disease have muscle weakness and risk of triggering myotony or malignant hyperthermia due to the use of anesthetic agents and surgical stress. The objective of this report was to demonstrate a viable alternative for clavicle fracture surgery with upper trunk and supraclavicular nerve block, thus reducing the spread of local anesthetic to the phrenic nerve in a patient with muscular dystrophy. Case report: A 53-year-old male patient with Steinert's disease, associated with dyspnea, hoarseness and dysphagia, referred to the surgical theater for osteosynthesis of clavicle fracture. Upper limb (1 mL 0.75% ropivacaine) and supraclavicular nerve block (1 mL 0.75% ropivacaine in each branch) were combined with venous anesthesia with propofol under laryngeal mask (infusion pump target of 4 mcg.mL-1). Upon awakening, the patient had no pain or respiratory complaints. He was transferred to the ICU for immediate postoperative follow-up with discharge from this unit after 24 h without complications. Conclusions: The superior trunk and cervical plexus block associated with venous anesthesia under laryngeal mask, without the use of opioids, proved to be adequate in the case of a patient with clavicle fracture and Steinert's disease. With the use of ultrasonography in regional anesthesia it is possible to perform increasingly selective blocks, thus allowing greater security for the anesthetic-surgical procedure and lower morbidity for the patient.

Resumo Justificativa e objetivos: Bloqueios seletivos dos membros superiores guiados por ultrassom podem trazer grandes benefícios em pacientes portadores de doenças graves. Pacientes portadores da doença de Steinert apresentam fraqueza muscular e riscos de desencadear miotonia ou hipertermia maligna devido ao uso de agentes anestésicos e ao estresse cirúrgico. O objetivo deste relato foi mostrar uma opção viável para a cirurgia de fratura de clavícula com bloqueio do tronco superior e nervo supraclavicular, diminui-se assim a dispersão do anestésico local para o nervo frênico em paciente com distrofia muscular. Relato de caso: Paciente do sexo masculino, 53 anos, portador de doença de Steinert, associada a dispneia, rouquidão e disfagia. Encaminhado ao bloco cirúrgico para osteossíntese de fratura de clavícula. Feito bloqueio de tronco superior (1 mL ropivacaína a 0,75%) e de nervo supraclavicular (1 mL de ropivacaína 0,75 em cada ramificação) associado à anestesia venosa com propofol sob máscara laríngea (alvo de 4 mcg.mL-1 em bomba de infusão). Ao despertar, o paciente apresentava-se sem dor ou queixas respiratórias. Admitido em CTI para acompanhamento do pós-operatório imediato com alta dessa unidade após 24 horas sem intercorrências. Conclusões: O bloqueio do tronco superior e do plexo cervical associado à anestesia venosa sob máscara laríngea, sem uso de opioides, mostrou-se adequado no caso de fratura da clavícula em paciente com doença de Steinert. Com o uso da ultrassonografia em anestesia regional é possível fazer bloqueios cada vez mais seletivos e possibilitar assim maior segurança para o procedimento anestésico-cirúrgico e menor morbidade para o paciente.

[Supraclavicular nerve and superior trunk block for surgical treatment of clavicle fracture in a patient with Steinert's disease - Case report]. / Bloqueio do nervo supraclavicular e do tronco superior para tratamento cirúrgico de fratura de clavícula em paciente portador de doença de Steinert ­ Relato de caso.

BACKGROUND AND OBJECTIVES: Ultrasound-guided upper limb blocks may provide great benefits to patients with serious diseases. Patients with Steinert's disease have muscle weakness and risk of triggering myotony or malignant hyperthermia due to the use of anesthetic agents and surgical stress. The objective of this report was to demonstrate a viable alternative for clavicle fracture surgery with upper trunk and supraclavicular nerve block, thus reducing the spread of local anesthetic to the phrenic nerve in a patient with muscular dystrophy. CASE REPORT: A 53-year-old male patient with Steinert's disease, associated with dyspnea, hoarseness and dysphagia, referred to the surgical theater for osteosynthesis of clavicle fracture. Upper limb (1mL 0.75% ropivacaine) and supraclavicular nerve block (1mL 0.75% ropivacaine in each branch) were combined with venous anesthesia with propofol under laryngeal mask (infusion pump target of 4 mcg.mL-1). Upon awakening, the patient had no pain or respiratory complaints. He was transferred to the ICU for immediate postoperative follow-up with discharge from this unit after 24hours without complications. CONCLUSIONS: The superior trunk and cervical plexus block associated with venous anesthesia under laryngeal mask, without the use of opioids, proved to be adequate in the case of a patient with clavicle fracture and Steinert's disease. With the use of ultrasonography in regional anesthesia it is possible to perform increasingly selective blocks, thus allowing greater security for the anesthetic-surgical procedure and lower morbidity for the patient.

Mucins and Truncated O-Glycans Unveil Phenotypic Discrepancies between Serous Ovarian Cancer Cell Lines and Primary Tumours.

Optimal research results rely on the selection of cellular models capable of recapitulating the characteristics of primary tumours from which they originate. The expression of mucins (MUC16 and MUC1) and truncated O-glycans (Tn, STn and T) represents a characteristic footprint of serous ovarian carcinomas (SOCs). Therefore, selecting ovarian cancer (OVCA) cell lines that reflect this phenotype is crucial to explore the putative biological role of these biomarkers in the SOC setting. Here, we investigated a panel of OVCA cell lines commonly used as SOC models, and tested whether, when cultured in 2D and 3D conditions, these recapitulate the mucin and O-glycan expression profiles of SOCs. We further explored the role of truncating the O-glycosylation capacity in OVCAR3 cells through knockout of the COSMC chaperone, using in vitro and in vivo assays. We found that the majority of OVCA cell lines of serous origin do not share the mucin and truncated O-glycan footprint of SOCs, although 3D cultures showed a higher resemblance. We also found that genetic truncation of the O-glycosylation capacity of OVCAR3 cells did not enhance oncogenic features either in vitro or in vivo. This study underscores the importance of well-characterized cellular models to study specific features of ovarian cancer.

Peritoneal dissemination of ovarian cancer: role of MUC16-mesothelin interaction and implications for treatment.

INTRODUCTION: Peritoneal dissemination is a particular form of malignant progression in ovarian cancer, preceding hematogenic or lymphatic dissemination. Thus, prevention of peritoneal implantation of cancer cells is envisioned to inhibit neoplastic dissemination and therefore prolong disease remission and patient's survival. Areas covered: An extended review on the role of MUC16 (CA125) and mesothelin (MSLN), expressed in a high percentage of ovarian carcinomas, indicate that this duet is relevant for the contact between cancer cells and mesothelial cells in homotypic (cancer cell-cancer cell) and heterotypic (cancer cell-mesothelial cell) interactions. This review discusses the reasons underlying the clinical failure of immunotherapeutic strategies targeting MUC16. Clinical data on MSLN targeting agents such as antibody-based immunotoxins or antibody drug conjugates are also reviewed. The promising anti-tumor effect of CAR-T cells directed to MUC16 or MSLN is emphasized. New emerging strategies specifically disrupting the MUC16-MSLN interaction are at the forefront of this review, including TRAIL ligands bound to MSLN targeting MUC16 expressing cells and single chain monoclonal antibodies and immunoadhesins recognizing MSLN-MUC16 binding domains. Expert commentary: Based on existing evidences the authors advocate that agents targeting MUC16-MSLN may add to the therapeutic armamentarium directed to abrogate peritoneal homing of ovarian cancer.

Diagnosis, presence of endoparasites, and local knowledge on the infestation of the exotic giant African snail (gastropoda: pulmonata: achatinidae), in the urban zone of Rio Branco, Acre, Brazil / Diagnóstico, presença de endoparasitas e conhecimento local sobre a infestação do caracol gigante exótico africano (gastropoda: pulmonata: achatinidae), na zona urbana de Rio Branco, Acre, Brasil

Abstract The giant African land snail, Lissachatina fulica is considered to be one of the world's worst invader species. This snail can provoke major economic and public health problems in urban areas, in particular as a potential vector of nematodes that infect both humans and animals. In this context, the present study investigated the extent of the infestation of this exotic snail in the urban neighborhoods of the city of Rio Branco, verified the presence of endoparasites in these snails, and evaluated the knowledge of local residents with regard to the presence of this invader species. For this, daytime surveys were conducted between August 2015 and June 2016. For the analysis of endoparasites, 44 live specimens were sent to the National Reference Laboratory for Schistosomiasis-Malacology (LRNEM) of the Oswaldo Cruz Institute (FIOCRUZ). The knowledge of local residents in the infested neighborhoods was investigated using questionnaires with direct, closed questions. The exotic invader species (L. fulica) was detected in 24 of the 36 neighborhoods visited. A total of 858 L. fulica specimens were collected, of which, 329 were alive and 527 were dead. The total length of the shell ranged from 0.7 to 14.2 cm, with a mean±standard deviation of 4.8±2.21 cm. The density of snails in the areas surveyed varied from 0.34 individuals/m2 to 3.54 individuals/m2, while the mean density within the whole study area was estimated to be 0.54 individuals/m2. Mature eggs were found in only 9 (2.7%) of the 329 specimens dissected. The endoparasitological analysis revealed the presence of rhabditiform larvae in 84% of the specimens examined, as well as the nematodes Aelurostrongylus abstrusus (22.7% of the specimens) and Strongyluris sp. (2.2%). A total of 39 local residents were interviewed, and while all were conscious of the presence of the mollusk, none knew its origin or the most adequate way of dealing with it. The results of the study indicate an ample infestation of the city of Rio Branco by L. fulica, and confirmed a complete lack of intervention on the part of the local authorities for the implementation of measures foe the control and management of this pest within the urban zone of Rio Branco.

Resumo Conhecido como caracol gigante africano a espécie Lissachatina fulica é considerada uma das piores espécies invasoras do mundo. Em áreas urbanas pode causar grandes problemas econômicos e para a saúde pública por ser um potencial vetor de nematódeos de interesse médico e veterinário. Desta forma, o presente trabalho teve como objetivos averiguar a extensão da infestação do caracol exótico nos bairros da zona urbana da cidade de Rio Branco; verificar a presença de endoparasitos, bem como avaliar o conhecimento da população local em relação a presença desta espécie invasora. Para isso, foram realizadas coletas diurnas no período de agosto de 2015 a junho de 2016. Para verificar a presença de endoparasitos foram enviados 44 indivíduos vivos ao Laboratório de Referência Nacional para Esquistossomose-Malacologia (LRNEM) da Fundação Oswaldo Cruz (FIOCRUZ). A avaliação do grau de conhecimento dos moradores dos bairros infestados deu-se pela utilização de questionários com perguntas fechadas e diretas. A espécie exótica e invasora (L. fulica) foi detectada em 24 dos 36 bairros visitados. Dos 858 indivíduos coletados, 329 estavam vivos e 527 mortos. O comprimento total das conchas variou de 0,7 a 14,2 cm com uma média±desvio padrão de 4,8±2,21 cm. A densidade de indivíduos nas áreas amostradas variou do mínimo de 0,34 ao máximo de 3,54 indivíduos/m2 enquanto que a densidade média de espécimes tendo como base a área total amostrada foi de 0,54 indivíduos/m2. Somente em 2,7% (9) dos 329 espécimes dissecados foram encontrados ovos maduros. A busca por endoparasitos revelou a presença larvas rabditiformes em 84% dos espécimes investigados além dos nematódeos Aelurostrongylus abstrusus (22,7%) e Strongyluris sp. (2,2%). Ao todo foram entrevistados 39 moradores, onde verificou-se que eles têm consciência da presença do molusco mas desconhecem sua origem e a forma de manejá-lo adequadamente. Nossos resultados apontam para uma ampla infestação da espécie L. fulica na cidade de Rio Branco e constata a total ausência do poder público no que diz respeito a implementação de medidas de controle e manejo desta praga nos limites da cidade.

Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies.