Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition). Cliona celata pellets showed low polysaccharide content (bellow 38.5%) and almost no anti-HIV activity (<10% inhibition). Stelletta sp. pellets, although quite rich in polysaccharide (up to 97.3%), showed only modest bioactivity (<36% HIV-1 inhibition). Erylus discophorus pellets were among the richest in terms of polysaccharide content (up to 98%) and the most active against HIV-1 (up to 95% inhibition). Chromatographic fractionation of the polysaccharide pellet obtained from a specimen of Erylus discophorus (B161) yielded only modestly active fractions. However, we could infer that the active molecule is most probably a high molecular weight sulfated polysaccharide (>2000 kDa), whose mechanism is possibly preventing viral attachment and entry (fusion inhibitor)

Total Mass TCI driven by Parametric Estimation

This paper presents the Total Mass Target Controlled Infusion algorithm. The system comprises an On Line tuned Algorithm for Recovery Detection (OLARD) after an initial bolus administration and a Bayesian identification method for parametric estimation based on sparse measurements of the accessible signal. To design the drug dosage profile, two algorithms are here proposed. During the transient phase, an Input Variance Control (IVC) algorithm is used. It is based on the concept of TCI and aims to steer the drug effect to a predefined target value within an a priori fixed interval of time. After the steady state phase is reached the drug dose regimen is controlled by a Total Mass Control (TMC) algorithm. The mass control law for compartmental systems is robust even in the presence of parameter uncertainties. The whole system feasibility has been evaluated for the case of Neuromuscular Blockade (NMB) level and was tested both in simulation and in real cases

On Repairing Natural Language to SQL Queries

Data analysts use SQL queries to access and manipulate data on their databases. However, these queries are often challenging to write, and small mistakes can lead to unexpected data output. Recent work has explored several ways to automatically synthesize queries based on a user-provided specification. One promising technique called text-to-SQL consists of the user providing a natural language description of the intended behavior and the database's schema. Even though text-to-SQL tools are becoming more accurate, there are still many instances where they fail to produce the correct query. In this paper, we analyze when text-to-SQL tools fail to return the correct query and show that it is often the case that the returned query is close to a correct query. We propose to repair these failing queries using a mutation-based approach that is agnostic to the text-to-SQL tool being used. We evaluate our approach on two recent text-to-SQL tools, RAT-SQL and SmBoP, and show that our approach can repair a significant number of failing queries

Influence of mechanical stress in a packaged frequency-modulated MEMS accelerometer

Frequency modulated accelerometers composed of two double-ended tuning fork (DETF) resonators on a differential configuration were characterized for their sensitivity to force applied to their package. Commonly, differential architectures are employed to cancel common mode errors, such as the mechanical stress or temperature dependency. The device dependence to mechanical stress was experimentally measured for forces up to 15 N and a reduction of about 5.6 times was obtained on the differential measurement. Additionally, the silicon dies were glued to chip-carriers using two different glues with distinct properties, and their sensitivity to stress was compared. The effectiveness of a viscoelastic glue over an epoxy-based glue for stress decoupling was tested. Long-term measurements under constant force were experimentally performed and for a time period of approximately 100 min, the stress relaxation and creeping of the viscoelastic glue enabled the recovery to the initial output of the sensor.The first author is supported by FCT - Fundacao para a Ciencia e Tecnologia through the grant PDE/BDE/114564/2016. This work is supported by FCT with the reference project UID/EEA/04436/2019

Radiographic anatomy of the proximal femur: correlation with the occurrence of fractures

OBJECTIVE: To evaluate the correlation between radiographic parameters of the proximal femur anatomy and fractures. METHODS: Three hundred and five digital x-rays of the pelvis were analyzed in the anteroposterior view. Of these x-rays, twenty-seven showed femoral neck or transtrochanteric fractures. The anatomical parameters analyzed were: femoral neck width (FNW), femoral neck length (FNL), femoral axis length (FAL), cervicodiaphyseal angle (CDA), acetabular tear-drop distance (ATD) and great trochanter-pubic symphysis distance (GTPSD). The analysis was performed by comparing the results of the x-rays with and without proximal femoral fracture, to establish a correlation between them. RESULTS: No differences were found between the anatomical parameters of the groups with and without proximal femoral fracture. CONCLUSION: There was no association between anatomical changes in the proximal femur and greater susceptibility to fractures. Level of evidence IV, Cross-sectional Study.OBJETIVO: Avaliar se existe correlação entre parâmetros radiográficos da anatomia da região proximal do fêmur e a ocorrência de fraturas. MÉTODOS: Trezentas e cinco radiografias digitais da bacia foram analisadas na incidência ântero-posterior. Destas radiografias, vinte e sete apresentavam fratura do colo femoral ou transtrocantérica. Os parâmetros anatômicos analisados foram: Largura do colo femoral (LCF), comprimento do colo femoral (CCF), comprimento do eixo femoral (CEF), ângulo cérvico-diafisário (ACD), distância entre as lágrimas acetabulares (DLA) e a distância grande trocânter- sínfise púbica (DGTSP).Foram analisadas, comparativamente, as radiografias com e sem fratura da região proximal do fêmur, para verificar se existem parâmetros radiográficos que estão associados com maior probabilidade de ocorrência de fratura do colo femoral ou transtrocantérica. RESULTADOS: Não foi encontrada diferença entre os parâmetros anatômicos dos grupos com e sem fratura na região proximal do fêmur. CONCLUSÃO: Não foi encontrada nenhuma associação entre alterações anatômicas na região proximal do fêmur e maior susceptibilidade à ocorrência de fraturas. Nível de evidência IV, Estudo Transversal.Universidade Federal de Minas GeraisUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits

Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. The molecular mechanisms that control and fine-tune the formation of this type of gait are unknown. Here, we take advantage of one strain of domesticated rabbits, the sauteur d'Alfort, that exhibits an abnormal locomotion behavior defined by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this strain frequently adopt a bipedal gait using their front legs. Using a combination of experimental crosses and whole genome sequencing, we show that a single locus containing the RAR related orphan receptor B gene (RORB) explains the atypical gait of these rabbits. We found that a splice-site mutation in an evolutionary conserved site of RORB results in several aberrant transcript isoforms incorporating intronic sequence. This mutation leads to a drastic reduction of RORB-positive neurons in the spinal cord, as well as defects in differentiation of populations of spinal cord interneurons. Our results show that RORB function is required for the performance of saltatorial locomotion in rabbits.Author summaryRabbits and hares have a characteristic jumping gait composed of an alternate rhythmical movement of the forelimbs and a synchronous bilateral movement of the hindlimbs. We have now characterized a recessive mutation present in a specific strain of domestic rabbits (sauteur d'Alfort) that disrupts the jumping gait. The mutation causing this defect in locomotion pattern occurs in the gene coding for the transcription factor RORB that is normally expressed in many regions of the nervous system especially in the spinal cord dorsal horn. Our results show that expression of RORB is drastically reduced in the spinal cord of affected rabbits which results in a developmental defect. This study is an advance in our understanding how locomotion is controlled in vertebrates

Deep Venous Thrombosis and a Very Rare Finding: Inferior Vena Cava Infra-renal Segment Agenesis

Bilateral deep vein thrombosis (DVT) should prompt investigation for pro-thrombotic conditions and the exclusion of vascular compromise due to intrinsic and extrinsic factors. The authors present the case of a 47-year-old man admitted with bilateral DVT and diagnosed with inferior vena cava (IVC) infra-renal segment agenesis, and discuss the management of this rare condition

Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

Background: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. Methods: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-foldPRDX3, 2.6-foldSOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-foldSELS, 16-foldGLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). Conclusions: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Research and Education Institute, Hospital Sirio-LibanesHosp Sirio Libanes, Res & Educ Inst, Rua Prof Daher Cutait 69, BR-01539001 Sao Paulo, SP, BrazilUniv Sao Paulo, Sao Paulo State Canc Inst, Sao Paulo, BrazilHosp Serv Publ Estadual Sao Paulo, Sao Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Morphol Dept, Belo Horizonte, MG, BrazilUniv Sao Paulo, Sch Med, Heart Inst, Lab Immunol, Sao Paulo, BrazilUniv Estadual Paraiba, Ctr Ciencias & Tecnol, Campina Grande, BrazilLudwig Inst Canc Res, Sao Paulo, BrazilAC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, BrazilUniv Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Sao Paulo, Emergency Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilFAPESP: 10/52554-1Web of Scienc

Robust Control of Maintenance-Phase Anesthesia

In biomedical systems, feedback control can be applied whenever adequate sensors, actuators, and sufficiently accurate mathematical models are available. The key issue is the capacity of the control algorithm to tackle the large levels of uncertainty, both structured and unstructured, associated with patient dynamics. In the particular case of intravenous anesthesia considered here, manipulated variables are drug infusion rates, administered by syringe pumps, and the measured signal outputs are the levels of hypnosis or depth of anesthesia (DoA) and of neuromuscular blockade (NMB). Figure 1 provides an example of a loop closed for the control of NMB

Vitamin A deficiency and associated factors in children in urban areas

OBJETIVO: Analisar a prevalência da deficiência de vitamina A em crianças e os fatores associados. MÉTODOS: Estudo de corte transversal de base populacional realizado com 1.211 crianças de seis a 59 meses de idade, de ambos os sexos, procedentes da área urbana de nove cidades do estado da Paraíba, Brasil. O estado nutricional de vitamina A foi avaliado pelas concentrações séricas de retinol e presença de infecção subclínica avaliada pelas concentrações de proteína C-reativa. Foram investigadas as condições socioeconômicas, demográficas, de saneamento, além da suplementação prévia com vitamina A. Foram consideradas com deficiência de vitamina A as crianças com concentrações de retinol sérico < 0,70 µmol/L. Níveis séricos de vitamina A < 0,70 µmol/L com prevalência ≥ 20% foram considerados como grave problema de saúde pública. Análises uni e multivaridas foram conduzidas para testar associações estatísticas (p < 0,05). RESULTADOS: A prevalência de deficiência de vitamina A foi de 21,8% (IC95% 19,6;24,2), mostrando associação com a presença de infecção subclínica e ausência de água no domicílio. A prevalência de deficiência de vitamina A foi de 21,8% (IC95% 19,6;24,2). Após ajuste para confundimento, a deficiência de vitamina A mostrou-se associada com a presença de infecção subclínica e com a ausência de água no domicílio. A ocorrência da deficiência de vitamina A foi quatro vezes maior (IC95% 1,49;10,16) em crianças com infecção subclínica e sem água no domicilio, comparativamente às crianças sem infecção e com água no domicílio. CONCLUSÕES: Apesar das ações de prevenção e controle da deficiência de vitamina A, a hipovitaminose A ainda configura-se como um problema de saúde pública preocupante entre as crianças menores de cinco anos.OBJECTIVE To estimate the prevalence of vitamin A deficiency and its associated factors in children. METHODS A cross-sectional population-based study, involving 1,211 children of both sexes, aged between six and 59 months old, was carried out in the urban zone of 9 cities in the state of Paraiba, Northeastern Brazil. Vitamin A status was assessed by serum retinol levels (high performance liquid chromatography – HPLC) and subclinical infection was assessed by C-reactive protein concentrations. Socioeconomic, demographic and sanitation conditions, as well as vitamin A supplement intake, were also evaluated. Children with serum retinol concentrations RESULTS The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2), showing an association with subclinical infection and lack of indoor plumbing. The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2). After adjustment, vitamin A deficiency was found to be linked with subclinical infection and lack of indoor plumbing. Vitamin A deficiency was four times higher (CI95% 1.49;10.16) in children with subclinical infection whose homes were without indoor plumbing, compared to children who were not infected and with indoor plumbing in their homes. CONCLUSIONS Despite activities aimed at the prevention and control of vitamin A deficiency, hypovitaminosis A, remains a public health concern among children under five