Mechanisms of somatostatin-induced paradoxical increase in insulin secretion in the presence of arginine vasopressin in clonal [beta]-cell HIT-T15

We investigated the mechanism underlying somatostatin-induced increase in [Ca2+]i leading to insulin release in the presence of arginine vasopressin (AVP) in clonal beta-cell HIT-T15. Somatostatin increased [Ca2+]i and insulin release in a biphasic pattern, characterized by a sharp and transient increase followed by a rapid decline to the sub-basal level. Pretreatment with pertussis toxin, which inactivates Gi/Go, abolished the effects of somatostatin. U-73122, an inhibitor of phospholipase C, antagonized somatostatin-induced increase in [Ca2+] i. In Ca2+-free environment, somatostatin still increased [Ca2+]i, whereas depletion of intracellular Ca 2+ stores with thapsigargin, a microsomal Ca2+ ATPase inhibitor, abolished somatostatin\u27s effect. In the presence of bradykinin, another Gq-coupled receptor agonist, somatostatin also increased [Ca 2+]i, but not in the presence of isoproterenol (a Gs-coupled receptor agonist) or medetomidine (a Gi/Go-coupled receptor agonist). Utilizing selective agonists for each somatostatin receptor subtype (SSTRI-5) and PRL-2903, a specific SSTR2 antagonist, we characterized the receptor mediating the somatostatin signaling. In the presence of AVP, treatment with the SSTR2 agonist L-779,976 resulted in responses similar to those seen with somatostatin. L-779,976 increased both [Ca2+]i and insulin release in a dose-dependent manner. Treatment with L-779,976 alone did not alter [Ca2+] i or basal insulin release. In the presence of AVP, all other somatostatin receptor agonists failed to increase [Ca2+]i and insulin release. The effects of somatostatin and L779,976 were abolished by PRL-2903. Administration of antibody against the beta subunit of Gi/Go into single cells inhibited the increase in [Ca2+]i by somatostatin, but antibodies against Gialpha1/Gialpha2 and Gialpha3/Goalpha failed to do so. Somatostatin increased PIP2 synthesis from PIP in the presence and absence of AVP, whereas an increase in IP3 synthesis was observed only in the presence of AVP. Taken together, our study strongly suggests that activation of the SSTR2 coupled to Gi/Go by somatostatin increases PIP2 synthesis through the betagamma dimer. The PIP2 generated by somatostatin serves as additional substrate for preactivated PLC-beta, which hydrolyzes PIP2 to form IP3, leading to Ca2+ release from the endoplasmic reticulum and insulin release in clonal beta-cell HIT-T15. The increases in [C2+]i and insulin release are due to a cross-talk between Gq and Gi/Go, although not limited to the AVP and somatostatin receptors

Ultrasonographic Findings in Patients Examined in Cataract Detection-and-Treatment Campaigns: A Retrospective Study

INTRODUCTION: A cataract is defined as an opacity of any portion of the lens, regardless of visual acuity. In some advanced cases of cataracts, in which good fundus visualization is not possible, an ultrasound examination provides better assessment of the posterior segment of the globe. OBJECTIVES: This study aims to evaluate the ultrasonographic records of patients with advanced cataracts who were examined during cataract campaigns. METHODS: The ultrasonographic findings obtained from 215 patients examined in cataract campaigns conducted by the Hospital das Clínicas Department of Ophthalmology of the Faculdade de Medicina da Universidade de São Paulo between the years of 2005 and 2007 were evaluated, and the utility of this exam in changing the treatment procedures was studied. RESULTS: A total of 289 eyes from 215 patients were examined. Of the eyes examined, 77.5% presented with findings in the vitreous cavity and the posterior pole. A posterior vitreous detachment with no other complications was observed in 47.4% of the eyes. The remaining 30.1% presented with eye diseases that could result in a reduced visual function after surgery. The most frequent eye diseases observed were diffuse vitreous opacity (12.1% of the eyes) and detachment of the retina (9.3% of the eyes). DISCUSSION: In many cases, the ultrasonographic evaluation of the posterior segment revealed significant anomalies that changed the original treatment plan or contra-indicated surgery. At the very least, the evaluation was useful for patient counseling. CONCLUSION: The ultrasonographic examination revealed and differentiated between eyes with cataracts and eyes with ocular abnormalities other than cataracts as the cause of poor vision, thereby indicating the importance of its use during ocular evaluation

Comparative study of ultrasound images obtained with 10MHz and 20 MHz probes in the evaluation of the abnormalities of the posterior segment of the globe

A ecografia se constitui em método importante na avaliação de anormalidades do segmento posterior do globo ocular. OBJETIVO: Comparar as vantagens e desvantagens da sonda de 10 e 20 MHz da ultra-sonografia B-scan, na avaliação de imagens do segmento posterior do globo ocular. MÉTODOS: Pacientes acompanhados no ambulatório do Hospital das Clínicas da USP (HCFMUSP) entre fevereiro de 2006 e abril de 2007 foram submetidos a exame ultra-sonográfico usando o aparelho CINE-Scan® (Quantel Medical Inc.) com sondas de 10 e 20 MHz. Os pacientes foram examinados por três oftalmologistas experientes, em decúbito dorsal, após instilação de colírio de tetracaína a 1%, inicialmente com a sonda sobre as pálpebras e em seguida diretamente em contato com a esclera ou córnea. As imagens obtidas com sondas de 10 e 20 MHz foram comparadas entre si, durante e após a realização do exame. RESULTADOS: A sonda de 20 MHz mostrou-se superior na avaliação da detecção, forma e limites de estruturas do pólo posterior e a de 10 MHz avaliou com mais detalhes o humor vítreo. Não foram encontradas diferenças nas imagens obtidas com exame transpalpebral ou transescleral com a sonda de 10 MHz. Com a sonda de 20 MHz, as imagens obtidas em contato direto com o globo ocular apresentaram melhor qualidade. CONCLUSÕES: As sondas de 10 e 20 MHz têm diferentes intervalo de alcance ideal, assim como diferentes meios específicos de aquisição de melhores imagens.The ultrasound is an important method in the evaluation of abnormalities of the posterior segment of the eye. PURPOSE: To compare the advantages and disadvantages of 10 and 20 MHz probe on B- scanning ultra-sonography in evaluation of vitreous and posterior pole diseases, providing recommendations for their use. METHODS: Patients from Hospital das Clinicas of the University of São Paulo (HC-FMUSP), attended between February 2006 and April 2007, were submitted to ultrasound exams using CINE-Scan® (Quantel Medical Inc) B-scan with 10 and 20MHz probe. The patients were examined by three experienced ophthalmologists, in horizontal dorsal position, after instillation of tetracaine 1% drops, first with the probe in direct contact with eyelids, and then with the probe placed directly in contact with the sclera or cornea. Theimages obtained were compared immediately during and after the examination. RESULTS: The 20 MHz probe reveled a superior resolution to study details, like shape and limits, on the posterior pole, and the 10 MHz probe provided better evaluation on vitreous humor. There were no differences if the exam was performed on eyelids or directly on sclera with the 10 MHz probe, but with the 20 MHz probe, the images had better resolution when the probe was used in direct contact with the eye. CONCLUSIONS: The 10 and 20 probes have different ideal range of reach, as different better specific means of image achieving

Comparative Pharmacokinetics of Orbifloxacin Following a Single Intravenous or Oral Administration to Healthy and Diabetic Rats

The single-dose disposition kinetics of orbifloxacin was determined in clinically healthy and diabetic rats  after intravenous or oral administration of 5 mg/kg body weight. Orbifloxacin concentrations were determined  by HPLC with fluorescence detection. The HPLC method was sensitive, specific and repeatable. A  systemic bioavailability of 99.1% and 108 %, and a Cmax of 6.55 } 1.09 μg /mL and 8.63 } 1.09 μg /mL were  observed in healthy and diabetic rats, respectively. The terminal half-life after intravenous and oral administration  was 4.17 } 0.38 h and 4.03 } 0.41 h for healthy and 2.31 } 0.34 h and 3.03 } 0.28 h for diabetic  rats. Orbifloxacin was cleared more rapidly in diabetic rats (0.15 } 0.01 L/kg.h) than healthy group (0.11 }  0.01 L/kg.h), with longer mean resident time (MRT) values observed in the latter. Other kinetic parameters  were almost the same between the healthy and diabetic groups. This investigation revealed that a dose of 5  mg/kg orbifloxacin can be safely and effectively used to combat infections in rats of either group associated  with susceptible bacteria.

A DNA barcode library for mangrove gastropods and crabs of Hong Kong and the Greater Bay Area reveals an unexpected faunal diversity associated with the intertidal forests of Southern China

BACKGROUND: Mangroves are tropical and subtropical intertidal forests colonising sheltered coasts across the world. They host a unique faunal community, dominated by brachyuran crabs and gastropods. These invertebrates strongly contribute to the functionality of the entire forest. The reliable assessment of mangrove faunal diversity is, thus, a crucial step for efficient management and conservation plans, but it is hindered by difficulties in species identification. Here we provide a verified DNA barcode library for brachyuran crabs and gastropods inhabiting the mangroves of the Greater Bay Area, Southern China. In particular, we collected and morphologically identified 1100 specimens of mangrove associated brachyuran crabs and gastropods. The partial sequences of the mtDNA cytochrome oxidase subunit I gene were obtained from 275 specimens. Barcode sequences were then used to delineate Molecular Operational Taxonomic Units (MOTUs), employing three different delimitation methods: the automatic barcode gap discovery (ABGD) method, the general mixed Yule coalescent (GMYC) model and a Bayesian implementation of the Poisson tree processes (bPTP) model. RESULTS: By integrating DNA barcodes with morphology, we identified 44 gastropod species and 58 brachyuran species associated with Hong Kong mangroves, with five and seven new records, for gastropods and crabs, respectively, for the Greater Bay Area. The delineation of MOTUs based on barcode sequences revealed a strong congruence between morphological and molecular identification for both taxa, showing the high reliability of the barcode library. CONCLUSIONS: This study provides the first reference barcode library for mangrove-associated macrobenthic fauna in the Greater Bay Area and represents a reliable tool to management and conservation plans. Our molecular analyses resolved long lasting taxonomic misidentifications and inconsistencies and updated the knowledge on the geographical distribution of Asian mangrove associated fauna, ultimately highlighting a level of biodiversity higher than previously thought for Southern China. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12862-021-01914-6

UM MODELO DE CONTATO SÓLIDO-SÓLIDO PARA O MÉTODO DE PARTÍCULAS MOVING PARTICLE SIMULATION

Problemas de interação fluído-estrutura com presença de superfície livre e sólidos livres para deslocar são fenômenos hidrodinâmicos altamente não lineares e de elevada complexidade, que trazem grandes desafios para a modelagem e simulação computacional. Nos casos de contato ou colisão entre sólidos, normalmente é necessário realizar algum tratamento específico para impedir a penetração entre corpos. Nesse contexto, o objetivo deste trabalho é contribuir para o desenvolvimento de uma técnica de simulação dos fenômenos hidráulicos e costeiros que envolvem a interação entre fluídos e sólidos apresentando um modelo de contato sólido-sólido para o método Moving Particle Simulation (MPS). O MPS é um método baseado na discretização do domínio em partículas, sem utilização de malha, e capaz de modelar geometrias complexas com grandes deslocamentos e deformação, incluindo superfícies livres com fragmentação e junção de fluídos e presença de multicorpos. O modelo de contato sólido-sólido proposto visa estender as funcionalidades do MPS, simplificando forças interfaciais por meio de um sistema massa-mola-amortecedor, de forma a reproduzir as propriedades macroscópicas da interação entre multicorpos. Comparações entre resultados numéricos e analíticos são realizados para calibração de constantes do modelo. O modelo é aplicado para um caso de carregamento de sólido livre em escoamento com superfície livre, e comparado com resultados numéricos e experimentais

Hifocus Helix™ Electrode Insertion: Surgical Approach.

Cochlear implants have been used for almost 30 years as a device for the rehabilitation of individuals with severe-to-profound hearing loss. One of the important aspects of cochlear implantation is the type of electrode selected and proper insertion of the electrode array in scala tympani to minimize cochlear damage. The HiFocus Helix™ electrode is a precurved design aimed at placing the electrode contacts close to the spiral ganglion cells in the modiolus. The prescribed insertion techniques are intended to minimize the likelihood of damage to the basilar membrane or lateral wall of the cochlea. To describe the first insertion of a HiFocus Helix™ electrode in Brazil exposing surgical particularities and device details in a patient with profound hearing loss, due to Mondini's dysplasia. No problems were encountered during the surgical procedure. The patient experienced improvement in hearing thresholds and speech perception. The HiFocus Helix™ electrode proved easy to insert and provided expected hearing benefits for the patient. This manuscript indicates that the HiResolution™ Bionic Ear System with HiFocus Helix™ electrode comprise a cochlear implant system that is practical and beneficial for the treatment of severe-to-profound hearing loss.830

State-machine replication for planet-scale systems

Online applications now routinely replicate their data at multiple sites around the world. In this paper we present Atlas, the first state-machine replication protocol tailored for such planet-scale systems. Atlas does not rely on a distinguished leader, so clients enjoy the same quality of service independently of their geographical locations. Furthermore, client-perceived latency improves as we add sites closer to clients. To achieve this, Atlas minimizes the size of its quorums using an observation that concurrent data center failures are rare. It also processes a high percentage of accesses in a single round trip, even when these conflict. We experimentally demonstrate that Atlas consistently outperforms state-of-The-Art protocols in planet-scale scenarios. In particular, Atlas is up to two times faster than Flexible Paxos with identical failure assumptions, and more than doubles the performance of Egalitarian Paxos in the YCSB benchmark.H2020 - Horizon 2020 Framework Programme(825184