Resultados quirúrgicos de la herniorrafia inguinal en los pacientes mayores de 80 años: Revisión sistemática y metaanálisis / Surgical outcomes of inguinal herniorrhaphy in patients over 80 yearsof age: Systematic review and meta-analysis

Introducción. Los pacientes octogenarios y nonagenarios conforman un grupo etario en progresivo crecimiento. La hernia inguinal es una patología que aumenta progresivamente con la edad. Este trabajo tuvo como objetivo conocer los resultados quirúrgicos de los pacientes mayores de 80 años a quienes se les realizó herniorrafía inguinal. Métodos. De acuerdo con las guías PRISMA, se realizó una revisión sistemática de PubMed, Embase y Google Scholar. Se incluyeron estudios que reportaron la incidencia de complicaciones y mortalidad después de una herniorrafía inguinal en los pacientes octogenarios y nonagenarios. Se calculó la proporción de pacientes con complicaciones después de una herniorrafía inguinal según los datos presentados, con su respectivo intervalo de confianza del 95 %. Resultados. Catorce estudios reportaron un total de 19.290 pacientes, entre quienes se encontró una incidencia acumulada de infección del sitio operatorio de 0,5 % (IC95% 0,460 - 0,678), seroma de 8,7 % (IC95% 6,212 - 11,842), hematoma de 2,6 % (IC95% 2,397 - 2,893), dolor crónico de 2,1 % (IC95% 0,778 - 4,090) y recidiva de 1,2 % (IC95%0,425 - 2,284), para una morbilidad de 14,7 % (IC95% 9,525 - 20,833). Conclusión. Las complicaciones de la herida quirúrgica, el dolor crónico y la recidiva en los pacientes mayores de 80 años a quienes se les realiza herniorrafia inguinal son comparables con las de la población general.

Introduction. Octogenarian and nonagenarian patients constitute a progressively growing age group. Inguinal hernia is a pathology that increases with age. This study aims to understand the surgical outcomes of inguinal herniorrhaphy in patients over 80 years of age. Methods. A systematic review of PubMed, Embase, and Google Scholar was conducted following PRISMA guidelines. Studies reporting the incidence of complications and mortality after inguinal herniorrhaphy in octogenarian and nonagenarian patients were included. The proportion of patients with complications after inguinal herniorrhaphy was calculated based on the data presented, with its respective 95% confidence interval. Results. Fourteen studies reported a total of 19,290 patients, among whom a cumulative incidence of surgical site infection of 0.5 (95% CI 0.460 ­ 0.678), seroma of 8.7% (95% CI 6.212 ­ 11.842), hematoma of 2.6% (95% CI 2.397 ­ 2.893), chronic pain 2.1% (95% CI 0.778 ­ 4.090), recurrence 1.2% (95% CI 0.425 ­ 2.284), and morbidity 14.7% (95% CI 9.525 ­ 20.833) were found. Conclusion. Surgical wound complications, chronic pain, and recurrence in patients over 80 years of age undergoing inguinal herniorrhaphy are comparable to those in the general population.

Alamandine, a protective component of the renin-angiotensin system, reduces cellular proliferation and interleukin-6 secretion in human macrophages through MasR-MrgDR heteromerization.

Alamandine (ALA) exerts protective effects similar to angiotensin (Ang) (1-7) through Mas-related G protein-coupled receptor type D receptor (MrgDR) activation, distinct from Mas receptor (MasR). ALA induces anti-inflammatory effects in mice but its impact in human macrophages remains unclear. We aimed to investigate the anti-inflammatory effects of ALA in human macrophages. Interleukin (IL)-6 and IL-1ß were measured by ELISA in human THP-1 macrophages and human monocyte-derived macrophages exposed to lipopolysaccharide (LPS). Consequences of MasR-MrgDR heteromerization were investigated in transfected HEK293T cells. ALA decreased IL-6 and IL-1ß secretion in LPS-activated THP-1 macrophages. The ALA-induced decrease in IL-6 but not in IL-1ß was prevented by MasR blockade and MasR downregulation, suggesting MasR-MrgDR interaction. In human monocyte-derived M1 macrophages, ALA decreased IL-1ß secretion independently of MasR. MasR-MrgDR interaction was confirmed in THP-1 macrophages, human monocyte-derived macrophages, and transfected HEK293T cells. MasR and MrgDR formed a constitutive heteromer that was not influenced by ALA. ALA promoted Akt and ERK1/2 activation only in cells expressing MasR-MrgDR heteromers, and this effect was prevented by MasR blockade. While Ang-(1-7) reduced cellular proliferation in MasR -but not MrgDR- expressing cells, ALA antiproliferative effect was elicited in cells expressing MasR-MrgDR heteromers. ALA also induced an antiproliferative response in THP-1 cells and this effect was abolished by MasR blockade, reinforcing MasR-MrgDR interaction. MasR-MrgDR heteromerization is crucial for ALA-induced anti-inflammatory and antiproliferative responses in human macrophages. This study broaden our knowledge of the protective axis of the RAS, thus enabling novel therapeutic approaches in inflammatory-associated diseases.

Adipose tissue plasticity mediated by the counterregulatory axis of the renin-angiotensin system: Role of Mas and MrgD receptors.

The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.

Counter-regulatory RAS peptides: new therapy targets for inflammation and fibrotic diseases?

The renin-angiotensin system (RAS) is an important cascade of enzymes and peptides that regulates blood pressure, volume, and electrolytes. Within this complex system of reactions, its counter-regulatory axis has attracted attention, which has been associated with the pathophysiology of inflammatory and fibrotic diseases. This review article analyzes the impact of different components of the counter-regulatory axis of the RAS on different pathologies. Of these peptides, Angiotensin-(1-7), angiotensin-(1-9) and alamandine have been evaluated in a wide variety of in vitro and in vivo studies, where not only they counteract the actions of the classical axis, but also exhibit independent anti-inflammatory and fibrotic actions when binding to specific receptors, mainly in heart, kidney, and lung. Other functional peptides are also addressed, which despite no reports associated with inflammation and fibrosis to date were found, they could represent a potential target of study. Furthermore, the association of agonists of the counter-regulatory axis is analyzed, highlighting their contribution to the modulation of the inflammatory response counteracting the development of fibrotic events. This article shows an overview of the importance of the RAS in the resolution of inflammatory and fibrotic diseases, offering an understanding of the individual components as potential treatments.

A Vibration Analysis for the Evaluation of Fuel Rail Pressure and Mass Air Flow Sensors on a Diesel Engine: Strategies for Predictive Maintenance.

This research focuses on the analysis of vibration of a compression ignition engine (CIE), specifically examining potential failures in the Fuel Rail Pressure (FRP) and Mass Air Flow (MAF) sensors, which are critical to combustion control. In line with current trends in mechanical system condition monitoring, we are incorporating information from these sensors to monitor engine health. This research proposes a method to validate the correct functioning of these sensors by analysing vibration signals from the engine. The effectiveness of the proposal is confirmed using real data from a Common Rail Direct Injection (CRDi) engine. Simulations using a GT 508 pressure simulator mimic FRP sensor failures and an adjustable potentiometer manipulates the MAF sensor signal. Vibration data from the engine are processed in MATLAB using frequency domain techniques to investigate the vibration response. The results show that the proposal provides a basis for an efficient predictive maintenance strategy for the MEC engine. The early detection of FRP and MAF sensor problems through a vibration analysis improves engine performance and reliability, minimizing downtime and repair costs. This research contributes to the advancement of monitoring and diagnostic techniques in mechanical engines, thereby improving their efficiency and durability.

Unraveling the crosstalk between renin-angiotensin system receptors.

The renin-angiotensin system (RAS) plays a key role in blood pressure regulation. The RAS is a complex interconnected system composed of two axes with opposite effects. The pressor arm, represented by angiotensin (Ang) II and the AT1 receptor (AT1R), mediates the vasoconstrictor, proliferative, hypertensive, oxidative, and pro-inflammatory effects of the RAS, while the depressor/protective arm, represented by Ang-(1-7), its Mas receptor (MasR) and the AT2 receptor (AT2R), opposes the actions elicited by the pressor arm. The AT1R, AT2R, and MasR belong to the G-protein-coupled receptor (GPCR) family. GPCRs operate not only as monomers, but they can also function in dimeric (homo and hetero) or higher-order oligomeric states. Due to the interaction with other receptors, GPCR properties may change: receptor affinity, trafficking, signaling, and its biological function may be altered. Thus, heteromerization provides a newly recognized means of modulation of receptor function, as well as crosstalk between GPCRs. This review is focused on angiotensin receptors, and how their properties are influenced by crosstalk with other receptors, adding more complexity to an already complex system and potentially opening up new therapeutic approaches.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan / Caracterização molecular de isolados de Aeromonas hydrophila de peixes doentes no distrito de Kasur, Punjab, Paquistão

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Breaking bad news in ophthalmology: a literature review / Comunicação de más notícias em oftalmologia: uma revisão de literatura

ABSTRACT Medical specialties have recognized that breaking bad news assists clinical practice by mitigating the impact of difficult conversations. This scenario also encourages various studies on breaking bad news in ophthalmology since certain ocular diagnoses can be considered bad news. Thus, the objective is to review the scientific literature on breaking bad news in ophthalmology. The literature databases like MEDLINE/PUBMED, EMBASE, LILACS, SCOPUS, COCHRANE, and SCIELO, were screened for related research publications. Two independent reviewers read all the articles and short-listed the most relevant ones. Seven articles, in the formats of original article, review, editorial, oral communication, and correspondence, were reviewed. Conclusively it reveals that ophthalmologists are concerned with communicating bad news effectively but lack related studies. Nevertheless, there is a growing realization that training in breaking bad news can increase physicians' confidence during communication, thus, benefiting the therapeutic relationship with the patient and his family. Therefore, it would be valuable to include breaking bad news training in the curriculum of residencies.

RESUMO O reconhecimento sobre a comunicação de más notícias como mitigadora de conversas difíceis por outras especialidades médicas, incentiva o estudo desta temática na oftalmologia. Sendo assim, o objetivo deste estudo é revisar a produção de pesquisas científicas sobre a comunicação de más notícias em oftalmologia. Para isso, foi realizada uma revisão de literatura. As bases de dados utilizadas foram MEDLINE/PUBMED, EMBASE, LILACS, SCOPUS, COCHRANE e SCIELO. Dois revisores independentes leram todos os artigos e selecionaram a amostra final. Sete artigos foram escolhidos nos formatos de artigo original, revisão, editorial, comunicação oral e correspondência. Os oftalmologistas estão preocupados em comunicar as más notícias de forma eficaz, mas faltam estudos sobre o tema. No entanto, há uma crescente percepção de que o treinamento de comunicação de más notícias aumenta a confiança dos médicos na comunicação, beneficiando a relação terapêutica. Portanto, seria valioso incluir este treinamento no currículo das residências.

Controversias Diagnósticas en la Clasificación Internacional de las Cefaleas, III Edición / Diagnostic controversies on the International Classifica tion of Headaches Disorders, III Edition

Resumen La revisión consideró los puntos de conflicto que pue dan llevar a confusión en el uso diario de la clasificación internacional de las cefaleas (ICHD-III). Se evaluaron tanto las controversias al momento de confeccionar los criterios como las superposiciones producidas tras su utilización en la práctica diaria, argumentado a través de bibliografía científica. Como puntos relevantes, la anamnesis de un paciente con cefalea debe indicar la intensidad del dolor como así también la duración del episodio doloroso y si su localización es estrictamente unilateral. Estos puntos podrán ser de ayuda en los casos de dolor moderado que no cumplan en forma absoluta los criterios para ninguna de las cefaleas primarias, dilema frecuente en la práctica diaria.

Abstract The review considered points of conflict that may lead to confusion in the daily use of the International Classification of Headache Disorders (ICHD-III). Both the controversies at the time of preparing the criteria and the overlaps produced after their use in daily practice were evaluated, argued through scientific bib liography. As relevant points, the anamnesis of a patient with headache should indicate the intensity of the pain as well as the duration of the painful episode and if its location is strictly unilateral. These points may be help ful in cases of moderate pain that do not fully meet the criteria for any of the primary headaches, a frequent dilemma in daily practice.

The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN). RESULTS: Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect. CONCLUSIONS: Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.

G-protein-coupled receptor MAS deletion produces a preeclampsia-like phenotype in FVB/N mice.

BACKGROUND: An unbalance in the renin-angiotensin (Ang) system (RAS) between the Ang II/AT1 and Ang-(1-7)/Mas axis appears to be involved in preeclampsia (PE), in which a reduction in Ang-(1-7) was observed. Here, we tested whether the reduction in the activity of the Ang-(1-7)/Mas axis could be a contributing factor for the development of PE, using Mas-deficient (Mas-/-) mice. METHODS AND RESULTS: Cardiovascular parameters were evaluated by telemetry before, during pregnancy and 4 days postpartum in 20-week-old Mas-/- and wild-type (WT) female mice. Mas-/- mice presented reduced arterial blood pressure (BP) at baseline (91.3 ± 0.8 in Mas-/- vs. 94.0 ± 0.9 mmHg in WT, Diastolic, P<0.05). However, after the 13th day of gestation, BP in Mas-/- mice started to increase, time-dependently, and at day 19 of pregnancy, these animals presented a higher BP in comparison with WT group (90.5 ± 0.7 in Mas-/- vs. 80.3 ± 3.5 mmHg in WT, Diastolic D19, P<0.0001). Moreover, pregnant Mas-/- mice presented fetal growth restriction, increase in urinary protein excretion as compared with nonpregnant Mas-/-, oliguria, increase in cytokines, endothelial dysfunction and reduced ACE, AT1R, ACE2, ET-1A, and eNOS placental mRNA, similar to some of the clinical manifestations found in the development of PE. CONCLUSIONS: These results show that Mas-deletion produces a PE-like state in FVB/N mice.

First Report of Aeromonas veronii as an Emerging Bacterial Pathogen of Farmed Nile Tilapia (Oreochromis niloticus) in Brazil.

Brazil is one of the world's leading producers of Nile tilapia, Oreochromis niloticus. However, the industry faces a major challenge in terms of infectious diseases, as at least five new pathogens have been formally described in the last five years. Aeromonas species are Gram-negative anaerobic bacteria that are often described as fish pathogens causing Motile Aeromonas Septicemia (MAS). In late December 2022, an epidemic outbreak was reported in farmed Nile tilapia in the state of São Paulo, Brazil, characterized by clinical signs and gross pathology suggestive of MAS. The objective of this study was to isolate, identify, and characterize in vitro and in vivo the causative agent of this epidemic outbreak. The bacterial isolates were identified as Aeromonas veronii based on the homology of 16S rRNA (99.9%), gyrB (98.9%), and the rpoB gene (99.1%). A. veronii showed susceptibility only to florfenicol, while it was resistant to the other three antimicrobials tested, oxytetracycline, enrofloxacin, and amoxicillin. The lowest florfenicol concentration capable of inhibiting bacterial growth was ≤0.5 µg/mL. The phenotypic resistance of the A. veronii isolate observed for quinolones and tetracycline was genetically confirmed by the presence of the qnrS2 (colE plasmid) and tetA antibiotic-resistant genes, respectively. A. veronii isolate was highly pathogenic in juvenile Nile tilapia tested in vivo, showing a mortality rate ranging from 3 to 100% in the lowest (1.2 × 104) and highest (1.2 × 108) bacterial dose groups, respectively. To our knowledge, this study would constitute the first report of highly pathogenic and multidrug-resistant A. veronii associated with outbreaks and high mortality rates in tilapia farmed in commercial net cages in Brazil.

Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro.

Objective: The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. Materials and methods: The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN in vitro, a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. Results: The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 µM. Conclusion: This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.

Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.

Background: Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1: An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2: A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions: Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.

Structural and conformational changes on chitosan after green heterogeneous synthesis of phenyl derivatives.

Four aromatic acid compounds: benzoic acid (Bz), 4-hydroxyphenylpropionic acid (HPPA), gallic acid (GA) and 4-aminobenzoic acid (PABA) were covalently bonded to chitosan in order to improve water solubility at neutral pH. The synthesis was performed via a radical redox reaction in heterogeneous phase by employing ascorbic acid and hydrogen peroxide (AA/H2O2) as radical initiators in ethanol. The analysis of chemical structure and conformational changes on acetylated chitosan was also the focus of this research. Grafted samples exhibited as high as 0.46 M degree of substitution (MS) and excellent solubility in water at neutral pH. Results showed a correlation between the disruption of C3-C5 (O3…O5) hydrogen bonds with increasing solubility in grafted samples. Spectroscopic techniques such as FT-IR and 1H and 13C NMR showed modifications in both glucosamine and N-Acetyl-glucosamine units by ester and amide linkage at C2, C3 and C6 position, respectively. Finally, loss of crystalline structure of 2-helical conformation of chitosan after grafting was observed by XRD and correlated with 13C CP-MAS-NMR analyses.

Central angiotensin 1-7 triggers brown fat thermogenesis.

We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.

Caracterización del síndrome coronario agudo en pacientes octogenarios / Characterization of the acute coronary syndrome in octogenarian patients

Introducción: La edad representa uno de los mayores predictores de riesgo de complicaciones cardiovasculares en pacientes con síndrome coronario agudo. La prevalencia de este síndrome en el grupo de los pacientes octogenarios es elevada. Métodos: Estudio prospectivo de cohortes analítico de todos los pacientes ingresados en la unidad de cuidados coronarios intensivos del Hospital Universitario Comandante Manuel Fajardo de la Habana, entre el año 2016 y el 2020. Objetivo: Caracterizar la población de pacientes octogenarios con síndrome coronario agudo y las posibles asociaciones entre la ocurrencia de complicaciones intrahospitalarias no letales y los factores de riesgo cardiovasculares. Resultados: Prevaleció el sexo femenino (64,2 por ciento), los antecedentes de hipertensión arterial (89,7 por ciento), cardiopatía isquémica (66,7 por ciento), y el tabaquismo (32 por ciento). Se encontraron asociaciones estadísticas significativas entre el tipo de síndrome coronario agudo y la presencia de complicaciones cardiovasculares de cualquier tipo (p=0,006); el aumento de la creatinina se asoció con la presencia de complicaciones hemodinámicas (Mdn=97; Rango=97,52; p=0,012), así como también la fracción de eyección del ventrículo izquierdo mostró una asociación muy significativa con la presencia de complicaciones cardiovasculares de cualquier tipo (Mdn=59; Rango=63,3; p<0,001) y hemodinámicas (Rango=55,2; p<0,001). Conclusiones: Se caracterizó la población de pacientes octogenarios con síndrome coronario agudo con elevación del segmento ST se asoció con un aumento de las complicaciones cardiovasculares intrahospitalarias, de la misma manera que sucedió con el valor de la fracción de eyección del ventrículo izquierdo(AU)

Introduction: Age represents one of the greatest predictors of risk of cardiovascular complications in patients with acute coronary syndrome. The prevalence of this syndrome in the group of octogenarian patients is high. Objective: To characterize the population of octogenarian patients with acute coronary syndrome and the possible associations between the occurrence of non-lethal intrahospital complications and cardiovascular risk factors. Methods: This is a prospective analytical cohort study of all patients admitted to the intensive coronary care unit of Manuel Fajardo University Hospital in Havana, from 2016 to 2020. Results: The female sex (64.2percent), a history of arterial hypertension (89.7percent), ischemic heart disease (66.7percent), and smoking habits (32percent) outweighed. Significant statistical associations were found between the type of acute coronary syndrome and the presence of cardiovascular complications of any type (p=0.006); the increase in creatinine was associated with the presence of hemodynamic complications (Mdn=97; Range=97.52; p=0.012), as well as the left ventricular ejection fraction showed a highly significant association with the presence of cardiovascular complications of any type (Mdn=59; Range=63.3; p<0.001) and hemodynamic (Range=55.2; p<0.001). Conclusions: The octogenarian population of patients with ST-segment elevation acute coronary syndrome was characterized and was associated with an increase in in-hospital cardiovascular complications, in the same way that it happened with the value of the left ventricular ejection fraction(AU)

Application of 1H HR-MAS NMR-Based Metabolite Fingerprinting of Marine Microalgae.

Natural products from the marine environment as well as microalgae, have been known for the complexity of the metabolites they produce due to their adaptability to different environmental conditions, which has been an inexhaustible source of several bioactive properties, such as antioxidant, anti-tumor, and antimicrobial. This study aims to characterize the main metabolites of three species of microalgae (Nannochloropsis oceanica, Chaetoceros muelleri, and Conticribra weissflogii), which have important applications in the biofuel and nutrition industries, by 1H High-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR), a method which is non-destructive, is highly reproducible, and requires minimal sample preparation. Even though the three species were found in the same ecosystem and a superior production of lipid compounds was observed, important differences were identified in relation to the production of specialized metabolites. These distinct properties favor the use of these compounds as leaders in the development of new bioactive compounds, especially against environmental, human, and animal pathogens (One Health), and demonstrate their potential in the development of alternatives for aquaculture.

Mas receptor endocytosis and signaling in health and disease.

The renin angiotensin system (RAS) plays a major role in blood pressure regulation and electrolyte homeostasis and is mainly composed by two axes mediating opposite effects. The pressor axis, constituted by angiotensin (Ang) II and the Ang II type 1 receptor (AT1R), exerts vasoconstrictor, proliferative, hypertensive, oxidative and pro-inflammatory actions, while the depressor/protective axis, represented by Ang-(1-7), its Mas receptor (MasR) and the Ang II type 2 receptor (AT2R), opposes the actions elicited by the pressor arm. The MasR belongs to the G protein-coupled receptor (GPCR) family. To avoid receptor overstimulation, GPCRs undergo internalization and trafficking into the cell after being stimulated. Then, the receptor may induce other signaling cascades or it may even interact with other receptors, generating distinct biological responses. Thus, control of a GPCR regarding space and time affects the specificity of the signals transduced by the receptor and the ultimate cellular response. The present chapter is focused on the signaling and trafficking pathways of MasR under physiological conditions and its participation in the pathogenesis of numerous brain diseases.