Orofacial Deformities in 3 Related Rhesus Monkeys (Macaca mulatta) Resembling Human Binder's Syndrome.

Binder's syndrome is a rare congenital deformity characterized by midface hypoplasia, particularly around the nasomaxillary area. Genetic etiology or developmental failure caused by prenatal exposure to teratological agents has been considered. In this article, we present 3 related rhesus monkeys born with orofacial deformities similar to those found in infants with the Binder phenotype. For the first time, a primate biomodel for this condition is presented. The clinical description and association with management and environmental factors are discussed. These findings reinforce the knowledge about the relationship between possible vitamin K metabolism interference and Binder's syndrome.

Spontaneous Vitiligo in a Captive Rhesus Monkey (Macaca Mulatta).

Vitiligo affects a significant portion of human and animal populations. The disease causes irregular and multifocal progressive loss of fur, skin, and mucous membrane pigmentation due to the loss or absence of melanocytes. While etiopathogenesis is not completely understood, autoimmunity, environmental, and genetic factors are implicated We present a case report on a 16-y-old female rhesus macaque (Macaca mulatta ) with depigmented areas that are progressively increasing on the skin and coat and are distributed on the head and back. Histopathology revealed alterations compatible with vitiligo characterized by the absence of melanocytes in the epidermis and dermis. The clinical history and complementary exams support this diagnosis.

Congenital adactyly and oligodactyly with metatarsal hypoplasia in two rhesus monkeys.

Congenital digital defects, particularly adactyly and oligodactyly, have been reported frequently in humans, however, their occurrence in rhesus monkeys is rare, mainly in the hind limbs. We present here for the first time, two female rhesus monkeys with unilateral congenital toe defects with metatarsal involvement. One showing adactyly and the other oligodactyly. In this report, we present the clinical/radiological details of these cases as well as discuss the risk factors possibly involved, such as contact with pesticides and genetic factors.

Pulmonary Granuloma Is Not Always the Tuberculosis Hallmark: Pathology of Tuberculosis Stages in New World and Old World Monkeys Naturally Infected with the Mycobacterium tuberculosis Complex.

We present the pathology of monkeys naturally infected with Mycobacterium tuberculosis complex from five different colonies in Rio de Janeiro, Brazil. On the basis of gross and histopathological findings, the lesions were classified into chronic-active, extrapulmonary, early-activation or latent-reactivation stages. Typical granulomatous pneumonia was seen in 46.6% of cases (six rhesus monkeys [Macaca mulatta] and one Uta Hick's bearded saki [Chiropotes utahickae]). The absence of pulmonary granulomas did not preclude a diagnosis of tuberculosis (TB): classical granulomatous pneumonia was observed in the chronic-active and latent-reactivation stages but not in the extrapulmonary and early-activation stages. The early-activation stage was characterized by interstitial pneumonia with a predominance of foamy macrophages and molecular and immunohistochemical evidence of M. tuberculosis complex infection. TB should be considered as a cause of interstitial pneumonia in New World Monkeys. We recommend the use of immunohistochemistry and molecular analysis for diagnosis of TB, even when typical macroscopic or histological changes are not observed.

P2Y12 receptor antagonism inhibits proliferation, migration and leads to autophagy of glioblastoma cells.

Glioblastoma (GBM) is the most aggressive and lethal among the primary brain tumors, with a low survival rate and resistance to radio and chemotherapy. The P2Y12 is an adenosine diphosphate (ADP) purinergic chemoreceptor, found mainly in platelets. In cancer cells, its activation has been described to induce proliferation and metastasis. Bearing in mind the need to find new treatments for GBM, this study aimed to investigate the role of the P2Y12R in the proliferation and migration of GBM cells, as well as to evaluate the expression of this receptor in patients' data obtained from the TCGA data bank. Here, we used the P2Y12R antagonist, ticagrelor, which belongs to the antiplatelet agent's class. The different GBM cells (cell line and patient-derived cells) were treated with ticagrelor, with the agonist, ADP, or both, and the effects on cell proliferation, colony formation, ADP hydrolysis, cell cycle and death, migration, and cell adhesion were analyzed. The results showed that ticagrelor decreased the viability and the proliferation of GBM cells. P2Y12R antagonism also reduced colony formation and migration potentials, with alterations on the expression of metalloproteinases, and induced autophagy in GBM cells. Changes were observed at the cell cycle level, and only the U251 cell line showed a significant reduction in the ADP hydrolysis profile. TCGA data analysis showed a higher expression of P2Y12R in gliomas samples when compared to the other tumors. These data demonstrate the importance of the P2Y12 receptor in gliomas development and reinforce its potential as a pharmacological target for glioma treatment.

Mosquito odorant receptor sensitive to natural spatial repellents and inhibitory compounds.

Previously, we have identified an odorant receptor (OR) from the southern house mosquito Culex quinquefasciatus, CquiOR32, which responded to both odorants (agonists) and inhibitory compounds (antagonists). CquiOR32/CquiOrco-expressing oocytes responded to methyl salicylate and other odorants with inward (regular) currents but gave currents in the reverse direction when challenged with eucalyptol and other inhibitors. To determine whether hitherto unknown ORs show this intrareceptor inhibition, we have now examined two other receptors in the same cluster, CquiOR27 and CquiOR28. We cloned and tested four variants of CquiOR28, but none of the 250 compounds in our panel of odorants, including an Orco ligand candidate (OLC12), elicited inward or upward deflections of the current traces. By contrast, CquiOR27/CquiOrco-expressing oocytes gave robust, dose-dependent inward currents when challenged with γ-octalactone and other odorants. On the other hand, octylamine and other phenolic compounds elicited dose-dependent currents in the reverse direction. When stimulatory and inhibitory compounds were presented in binary mixtures, γ-octalactone-elicited inward currents were attenuated in a dose-dependent manner according to the concentration of octylamine. As part of our chemical ecology approach, we tested the repellency activity of the most potent ligands in the surface landing and feeding assay and a newly reported hand-in cage assay. Protection elicited by γ-octalactone did not differ significantly from that of DEET at the same dose. In the hand-in cage assay, a cream formulation of γ-octalactone showed 97.0 ± 1.3% protection, with 47.6 ± 8.3% and 1.4 ± 0.7% landings per trial in the hands covered with a control and γ-octalactone cream, respectively (N = 8, p = 0.0078, Wilcoxon matched-pairs signed-rank test).

Quantitative detection of SARS-CoV-2 RNA in nasopharyngeal samples from infected patients with mild disease.

Diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) cases is based on the count of real-time reverse transcription-plymerase chain reaction (RT-PCR) positive people. Viral load by real-time RT-PCR has been suggested as a biomarker of the SARS-CoV-2 infection. However, the association of viral load and severity of the disease is not yet resolved. Nasopharyngeal samples from 458 patients were tested by RT-PCR for SARS-CoV-2 diagnosis. Relative quantitation was made by the comparative threshold cycle (ΔΔCt ) formula between ORF1ab viral and RNase P housekeeping genes. Absolute viral load was calculate using a reference positive control. Most prevalent clinical signs were cough (75.8%), myalgia (66.7%), and fever (48.5%). Hypertension (18.2%), neurological diseases (15.1%), and asthma and hypothyroidism (12.1%) were most frequent comorbidities. Fever, either as an exclusive symptom or combined with others, was associated with high viral loads ( 2-∆∆Ct range, 35.65-155.16; 4.25-4.89 log10 RNA copies/test]). During the first week after onset of symptoms in mild patients up to 60 years-old was detected the peak of viral load. Children under 10 years old have a high viral load (313.84; 2.50) in the first 2 days postinfection with a sharp decline thereafter. Cases between 10 and 49 years old mostly showed low and moderate viral load during the first 2 days postinfection (range, 0.03 to 17.24; -1.50 to 1.24). Patients over 60 years old have high viral load up to the second week after the onset of symptoms (range, 25.32-155.42; 1.40-2.19), indicating the longer presence of the virus in them. These findings suggest the viral load in nasopharyngeal swabs would help to monitor the SARS-CoV-2 infection in mild coronavirus disease 2019 cases.

Geographical Distribution of Genetic Variants and Lineages of SARS-CoV-2 in Chile.

The pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide public health concern. First confined in China and then disseminated widely across Europe and America, SARS-CoV-2 has impacted and moved the scientific community around the world to working in a fast and coordinated way to collect all possible information about this virus and generate new strategies and protocols to try to stop the infection. During March 2020, more than 16,000 full viral genomes have been shared in public databases that allow the construction of genetic landscapes for tracking and monitoring the viral advances over time and study the genomic variations present in geographic regions. In this work, we present the occurrence of genetic variants and lineages of SARS-CoV-2 in Chile during March to April 2020. Complete genome analysis of 141 viral samples from different regions of Chile revealed a predominance of variant D614G like in Europe and the USA and the major presence of lineage B.1. These findings could help take control measures due to the similarity of the viral variants present in Chile, compared with other countries, and monitor the dynamic change of virus variants in the country.

Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile.

The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub-classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.

Inferolateral post-myocardial infarction pseudoaneurysm. A rare case report / Pseudoaneurisma pós-infarto inferolateral. Um raro relato de caso

ABSTRACT: We report the case of a 76-year-old male patient with a history of ST-segment elevation myocardial infarction (STEMI) for 3 years. He was admitted to the Emergency Room with a new chest pain episode that began 40 days before and was diagnosed with left ventricular (LV) pseudoaneurysm through 3D transthoracic echocardiography and cardiac magnetic resonance imaging scans. The patient underwent angiography of the coronary arteries, identifying lesions with a multiarterial pattern. Surgical treatment and LV aneurysmectomy were performed with good clinical evolution.

RESUMO: Relatamos um caso de paciente do sexo masculino, de 76 anos, com antecedente de infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) há 3 anos. Foi admitido na unidade de pronto-socorro com nova dor torácica de início há 40 dias, sendo diagnosticado com pseudoaneurisma do ventrículo esquerdo por meio de exames de imagem (ecocardiograma transtorácico tridimensional e ressonância magnética cardíaca), tendo sido submetido a estudo angiográfico das coronárias, com identificação de lesões com padrão multiarterial. Foi realizado tratamento cirúrgico, aneurismectomia do ventrículo esquerdo, com boa evolução clínica.

Upregulation of PIR gene expression induced by human papillomavirus E6 and E7 in epithelial oral and cervical cells.

The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells. The PIR expression was dependent on functional HR-HPV E6 and E7 oncoproteins even though the E7 oncoprotein had higher activity to induce PIR overexpression in comparison with E6. In addition, using an siRNA for PIR silencing in oral cells ectopically expressing HR-HPV E6/E7, there was a significant increase in E-cadherin transcripts and a decrease in Vimentin, Slug, Zeb and Snail transcripts, suggesting that HR-HPV-induced PIR overexpression is involved in epithelial-mesenchymal transition. Furthermore, migration of PIR-silenced cells was significantly decreased. Finally, using inhibitors of some specific pathways, it was found that EGFR/ERK and PI3 K/AKT signalling pathways are important for E7-mediated PIR overexpression. It can be concluded that PIR gene expression is highly dependent on the expression of HR-HPV oncoproteins and is important for EMT regulation.

Binding of a fluorescence reporter and a ligand to an odorant-binding protein of the yellow fever mosquito, Aedes aegypti.

Odorant-binding proteins (OBPs), also named pheromone-binding proteins when the odorant is a pheromone, are essential for insect olfaction. They solubilize odorants that reach the port of entry of the olfactory system, the pore tubules in antennae and other olfactory appendages. Then, OBPs transport these hydrophobic compounds through an aqueous sensillar lymph to receptors embedded on dendritic membranes of olfactory receptor neurons. Structures of OBPs from mosquito species have shed new light on the mechanism of transport, although there is considerable debate on how they deliver odorant to receptors. An OBP from the southern house mosquito, Culex quinquefasciatus, binds the hydrophobic moiety of a mosquito oviposition pheromone (MOP) on the edge of its binding cavity. Likewise, it has been demonstrated that the orthologous protein from the malaria mosquito binds the insect repellent DEET on a similar edge of its binding pocket. A high school research project was aimed at testing whether the orthologous protein from the yellow fever mosquito, AaegOBP1, binds DEET and other insect repellents, and MOP was used as a positive control. Binding assays using the fluorescence reporter N-phenyl-1-naphtylamine (NPN) were inconclusive. However, titration of NPN fluorescence emission in AaegOBP1 solution with MOP led to unexpected and intriguing results. Quenching was observed in the initial phase of titration, but addition of higher doses of MOP led to a stepwise increase in fluorescence emission coupled with a blue shift, which can be explained at least in part by formation of MOP micelles to house stray NPN molecules.

Terapia elétrica: desfibrilação e cardioversão de taquiarritmias / Electrical therapy: defibrillation and cardioversion of taquiarrhythmias

Esse artigo é uma revisão bibliográfica acerca do diagnóstico e do tratamento de taquiarritmias em situações de urgência e emergência, com foco nas indicações de cardioversão e desfibrilação. Ele aborda a utilização, técnica e complicações da terapia elétrica, bem como suas principais indicações: parada cardiorrespiratória em fibrilação e taquicardia ventricular, fibrilação e flutter atrial e taquicardia supraventricular com reentrada.

This article is a bibliographic review about the diagnosis and treatment of tachyarrythmias in urgency and emergency scenario, focusing on the indications of cardioversion and defibrillation. It approaches the utilization, technique and complications of electric therapy, as well as its main indications: cardiac arrest in ventricular fibrillation and tachycardia, atrial fibrillation and flutter and reentrancy supraventricular tachycardia.

Insuficiência arterial aguda de membros inferiores / Acute arterial insufficiency of lower limbs

Análise dos mecanismos fisiopatológicos, manifestações clínicas, diagnóstico e tratamento de oclusão arterial aguda.

Analysis of the pathophysiological mechanisms, clinical manifestations, diagnosis and treatment of acute arterial occlusion.

Estudio clínico-ecográfico de la fase ovulatoria, ciclos espontáneos e inducidos, concepcionales y no concepcionales / Clinico-ecographic study of the ovulatory phase, spontaneous and induced cycles, conceptional and non conceptional

Se presentan los resultados de 110 ciclos menstruales de 87 pacientes que fueron estudiadas con seguimiento ecográfico de la ovulación, determinación inmunológica de LH, curva de temperatura basal y estudio seriado del score cervical, desde el día -6 al día 0; el seguimiento ecográfico comprendió la determinación del diámetro folicular, el grosor endometrial y la presencia de líquido libre en el fondo del saco de Douglas. Se consideran sólo aquellas pacientes en que la última observación del folículo fue hecha hasta 24 horas de su desaparición, siendo éste el hecho que indica la ovulación, relacionándose las demás veriables con ello. Estas pacientes presentan ciclos espontáneos (47,3%), inducidos con epimestrol (28,2%) o clomifeno (24,5%) y resultaron embarazadas o no en este ciclo, 34,6%; 25,8% y 37,0% respectivamente. Fueron 36 casos con embarazo (32,7%). Las tres curvas de diámetro folicular para ciclos con embarazo resultaron notablemente similares, siendo el tamaño folicular preovulatorio de 21,5 mm. para ciclos espontáneos, 18,9 mm para ciclos inducidos con epimetrol y 20,7 mm para ciclos inducidos con clomifeno. El rango en los ciclos concepcionales fue de 15 a 27 mm, 15 a 22 mm y 14 a 27 mm, respectivamente. En 5 ciclos con embarazo (13,9%) no se observó líquido libre en el Douglas. La mayoría de los LH (+) se agrupan en los días -2 y -1 (21% y 50% respectivamente). Hubo una paciente que se embarazó y 2 que no se embarazaron que tuvieron LH iterativamente negativa. En el 50% de las pacientes que se embarazaron el Nadir térmico fue el día -1. En el grupo espontáneo concepcional no se observaron malos scores cervicales. El período de buen score es más largo en los grupos concepcionales espontáneos y con epimestrol. En el grupo de ciclos con embarazo no se observó disociación entre el día del mejor score y la ovulación, hecho que sí se observa en los ciclos no concepcionales