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1.
Front Pharmacol ; 15: 1403747, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211781

RESUMO

Background: Physiological changes in pregnancy may affect drug safety and efficacy, sometimes requiring dose adjustments. Pregnancy-adjusted doses, however, are missing for most medications. Increasingly, pharmacokinetic models can be used for antenatal dose finding. Given the novelty of this technique and questions regarding dose credibility, the acceptability of model-informed antenatal doses should be explored. Objective: We aimed to assess the willingness-to-use and preferred features for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women in European countries. Methods: A cross-sectional, web-based study drawing on two open surveys was performed between 8 September and 30 November 2022. Each survey comprised statements drawn from prior focus groups, associated with Likert-scales. Themes included respondents' information needs, search behaviours along with their willingness-to-use and preferred features for model-informed antenatal doses. The surveys were disseminated through professional societies, pregnancy websites and social media. A descriptive analysis was performed. Results: In total, 608 HCPs from different specialties and 794 pregnant women across 15 countries participated, with 81% of respondents across both groups in the Netherlands or Belgium. Among pregnant women, 31% were medical professionals and 85% used medication during pregnancy. Eighty-three percent of HCPs found current antenatal pharmacotherapy suboptimal and 97% believed that model-informed antenatal doses would enhance the quality of antenatal care. Most HCPs (93%) and pregnant women (75%) would be willing to follow model-informed antenatal doses. Most HCPs desired access to the evidence (88%), including from pharmacokinetic modelling (62%). Most pregnant women (96%) wanted to understand antenatal dosing rationales and to be involved in dosing decisions (97%). Conclusion: The willingness-to-use model-informed antenatal doses is high among HCPs and pregnant women provided that certain information needs are met.

2.
JAMA Netw Open ; 6(4): e239995, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37099296

RESUMO

Importance: There were over 45 000 suicides in the US in 2020, making suicide the 12th leading cause of death. If social vulnerability is associated with suicide rates, targeted interventions for at-risk segments of the population may reduce US suicide rates. Objective: To determine the association between social vulnerability and suicide in adults. Design, Setting, and Participants: This cohort study analyzed 2 county-level social vulnerability measures (the Social Vulnerability Index [SVI] and the Social Vulnerability Metric [SVM]) and US Centers for Disease Control and Prevention-reported county-level suicides from 2016 to 2020. Data were analyzed November and December 2022. Exposures: County-level variability in social vulnerability. Main Outcomes and Measures: The primary outcome measure was number of county-level adult suicides from 2016 to 2020, offset by county adult population during those years. The association between social vulnerability (measured using the SVI and the newly created SVM for 2018) and suicide was modeled using a bayesian-censored Poisson regression model to account for the CDC's suppression of county-level suicide counts of less than 10, adjusted for age, racial and ethnic minority, and urban-rural county characteristics. Results: From 2016 to 2020, there were a total of 222 018 suicides in 3141 counties. Comparing the least socially vulnerable (0% to 10%) to the most socially vulnerable (90% to 100%) counties, there was a 56% increase in suicide rate (17.3 per 100 000 persons to 27.0 per 100 000 persons) as measured by the SVI (incidence rate ratio, 1.56; 95% credible interval, 1.51-1.60) and an 82% increase in suicide rate (13.8 per 100 000 persons to 25.1 per 100 000 persons) as measured by the SVM (incidence rate ratio, 1.82; 95% credible interval, 1.72-1.92). Conclusions and Relevance: This cohort study found that social vulnerability had a direct association with risk for adult suicide. Reducing social vulnerability may lead to life-saving reduction in the rate of suicide.


Assuntos
Suicídio , Humanos , Adulto , Etnicidade , Vulnerabilidade Social , Estudos de Coortes , Teorema de Bayes , Grupos Minoritários
3.
Food Chem ; 419: 136086, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37030213

RESUMO

The fine, coarse and parent starches were isolated from pea flour by milling and air-classification. Their structural, thermal, physicochemical properties and in vitro digestibility were investigated. Particle Size Distribution showed the fine starch with the smallest unimodal distribution (18.33 and 19.02 µm) displayed higher degree of short-range molecular order and lower number of double helix structure. Scanning Electron Microscopy showed the morphology of the coarse starch granules as uniform in size and lacking protein particles on its smooth surface. Differential Scanning Calorimetry revealed the coarse starch had higher enthalpy changes while Rapid Visco Analysis showed higher peak, trough, and breakdown viscosities for the fine starch. In vitro digestibility featured the fine starch containing lower fast digesting starch contents, but with higher resistant starch content, indicating its resistance to enzymatic hydrolysis. The results could provide theoretical support for application of pea starch in functional foods and the manufacture of emerging starch products.


Assuntos
Farinha , Amido , Farinha/análise , Hidrólise , Pisum sativum/química , Amido/química , Viscosidade , Fenômenos Químicos
4.
Int J Phytoremediation ; 25(6): 728-736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35912832

RESUMO

The potential of phytoremediation of oil-based drill cuttings (OBDCs) contaminated soil was assessed by measuring the level of petroleum hydrocarbons reduction. The contamination experiment was simulated in a randomized complete block design by factorial of 6 × 3 × 2 × 2 for grass species (Pennisitum purpureum, Panicum maximum, Andropogon gayanus, Heteropogon contortus, Axonopus compressus, and Chloris virgata), drill cuttings treatments (0%, 25%, and 50% OBDCs contamination), time (0 day of planting and 105 days of harvesting), and growth stage (young and mature). The parameters assessed were total petroleum hydrocarbons (TPHs) in soils, roots, and shoots; bioconcentration factor in roots and shoots; and translocation factor. The TPH reductions achieved in 25% treatment level were young A. compressus (58.01%), mature P. purpureum, young A. gayanus and C. virgata (44.24%), young P. purpureum (27.67%), mature A. compressus (25.29%), mature H. contortus (2.56%), mature P. maximum (4.01%), and unplanted soils (2.10%). Thus young A. compressus, A. gayanus, C. virgata, and mature P. purpureum are recommended for TPH reduction in 25% OBDCs contaminated soils. Young P. purpureum and mature A. compressus can be used to achieve 25% - 27% TPH reduction.


Reduction of petroleum hydrocarbon in oil-based drill cuttings (OBDCs) contaminated soils using grass species without addition of fertilizers.Addition of Axonopus compressus and Chloris virgata as grass species with potential to reduce petroleum hydrocarbon in OBDCs contaminated soils.Growth stage of grass species is an important consideration for phytoremediation of OBDCs contaminated soil.Determination of phytoremediation mechanism in OBDCs contaminated soil.


Assuntos
Biodegradação Ambiental , Petróleo , Poaceae , Poluentes do Solo , Hidrocarbonetos , Solo , Microbiologia do Solo , Poluentes do Solo/análise
5.
Front Behav Neurosci ; 17: 1295969, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38515786

RESUMO

Here, we propose a model of remote memory (BaconREM), which is an extension of a previously published Bayesian model of context fear learning (BACON) that accounts for many aspects of recently learned context fear. BaconREM simulates most known phenomenology of remote context fear as studied in rodents and makes new predictions. In particular, it predicts the well-known observation that fear that was conditioned to a recently encoded context becomes hippocampus-independent and shows much-enhanced generalization ("hyper-generalization") when systems consolidation occurs (i.e., when memory becomes remote). However, the model also predicts that there should be circumstances under which the generalizability of remote fear may not increase or even decrease. It also predicts the established finding that a "reminder" exposure to a feared context can abolish hyper-generalization while at the same time making remote fear again hippocampus-dependent. This observation has in the past been taken to suggest that reminders facilitate access to detail memory that remains permanently in the hippocampus even after systems consolidation is complete. However, the present model simulates this result even though it totally moves all the contextual memory that it retains to the neo-cortex when context fear becomes remote.

6.
Learn Mem ; 29(9): 283-296, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36206390

RESUMO

There are sex differences in anxiety disorders with regard to occurrence and severity of episodes such that females tend to experience more frequent and more severe episodes. Contextual fear learning and generalization are especially relevant to anxiety disorders, which are often defined by expressing fear and/or anxiety in safe contexts. In contextual fear conditioning, a representation of the context must first be created, and then that representation must be paired with an aversive consequence. With some variation, the experiments presented here use a 3-d procedure in which day 1 consists of pre-exposure to the to-be-shocked context, day 2 consists of a single context-shock pairing after some placement-to-shock interval (PSI), and day 3 consists of testing in either the same or a novel context. With shorter pre-exposure periods, male rats showed more contextual fear, consistent with previous literature; however, after longer pre-exposure periods, female rats showed greater contextual fear. Additionally, while pre-exposure and PSI are both periods of time prior to the shock, it was found that they were not equivalent to each other. Animals with 120 sec of pre-exposure and a 30-sec PSI show a differential level and time course of fear expression than animals who received no pre-exposure and a 150-sec PSI, and this further depended on sex of the rat. Additionally, an experiment comparing recently versus remotely acquired contextual fear was run. Males were again shown to have greater contextual fear at both time points, and this contextual fear incubated/increased over time in males but not females. To facilitate identification of what processes caused sex differences, we used BaconX, a conceptual and computational model of hippocampal contextual learning. Computational simulations using this model predicted many of our key findings. Furthermore, these simulations suggest potential mechanisms with regard to hippocampal computation; namely, an increased feature sampling rate in males, which may account for the sex differences presented here and in prior literature.


Assuntos
Medo , Caracteres Sexuais , Animais , Comportamento Animal , Feminino , Generalização Psicológica , Hipocampo , Masculino , Ratos
7.
Food Funct ; 13(11): 5953-5970, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35587106

RESUMO

The bioaccessibility of carotenoids varies among different foods due to factors such as food matrix composition and type or extent of processing. Hence it is important to understand the extent to which these factors influence carotenoid bioaccessibility after the consumption and digestion of food. This study evaluated the carotenoid content, micellization efficiency, digestive stability, antioxidant activity and bioaccessibility of carotenoids as impacted by wheat cultivar and cooking duration among whole wheat flour (WWF) and refined semolina (RS) pasta. WWF and RS pasta were processed from three durum wheat cultivars (AAC Spitfire, CDC Precision, and Transcend) and cooked to al dente (Al), fully cooked (FCT) or overcooked (OC). The study showed that the wheat cultivar and cooking duration were significant functions of bioaccessible lutein in RS samples while only the cultivar influenced the bioaccessibility of zeaxanthin and lutein in WWF samples. In both WWF and RS, the effect of the cultivar on the bioaccessibility of lutein and zeaxanthin was similar and was as follows: Transcend > CDC Precision > AAC Spitfire. Cooking to Al significantly caused an increment in bioaccessible lutein in RS samples regardless of the wheat cultivar. This influence of cooking duration (Al > FCT > OC) was inversely related to the lutein concentrations in undigested pasta (OC = FCT > Al). DPPH scavenging activity among WWF samples was about 2-fold greater or more than that of RS samples regardless of the cultivar or cooking duration before and after digestion. Our data suggest that the effect of wheat cultivar and cooking duration modulates the bioaccessibility and antioxidant activity of RS and WWF pasta products.


Assuntos
Farinha , Triticum , Antioxidantes , Carotenoides/análise , Culinária , Digestão , Grão Comestível/química , Farinha/análise , Luteína , Triticum/química , Zeaxantinas
8.
J Undergrad Neurosci Educ ; 20(2): A166-A177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38323045

RESUMO

FraidyRat is a teaching tool that allows students to investigate the neural basis of fear conditioning and extinction using a virtual rat with a virtual brain. FraidyRat models well-known phenomena at both a behavioral and neural level. Students use virtual versions of tract tracing, systemic and intracerebrally infused drugs, neural recording, and electrical stimulation to understand the neural substrates underlying the observed behavior. This module helps students develop critical thinking skills in order to deduce immediate cause and effect as well as inductive reasoning to grasp the broader scheme. This module utilizes scaffolded instruction and formative assessment to shape the thinking of students as they unfold and discover the neural mechanisms responsible for fear conditioning and extinction in FraidyRat, which largely reflect what is found in real rats. Experience with this three-week module resulted in students showing significant gains in content knowledge as well as a trend toward gains in critical thinking. An attitudinal questionnaire showed that students had an overall positive experience. This module can be replicated at any institution with just a computer. All materials are available at: https://mdcune.psych.ucla.edu/modules/fraidy-rat.

9.
Food Res Int ; 150(Pt A): 110750, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34865768

RESUMO

The effect of simulated in vitro upper gut digestion on the phenolic composition and antioxidant properties of processed cowpea beans was studied. The samples comprised four cowpea cultivars: a cream, brownish-cream and two reddish-brown cultivars. Dry cowpea seeds were soaked in water, blended into paste and deep-fried in vegetable oil. The fried samples were taken through in vitro upper gut digestion followed by freeze-drying of the supernatant. Phenolic composition of extracts from the supernatants were determined using HPLC-MS. Radical scavenging activities were documented using the TEAC, ORAC and nitric oxide (NO) assays. In vitro digestion of the processed cowpeas resulted in phenolic-peptide complexes that were identified for the first time, and decreased extractable phenolic compounds. However, the radical scavenging activities increased. The processed cowpeas and their digests inhibited cellular NO production, and oxidative DNA and cellular damage. In conclusion, deep-fried cowpeas when consumed, could potentially help alleviate oxidative stress-related conditions.


Assuntos
Fabaceae , Vigna , Antioxidantes , Digestão , Fenóis
10.
PLoS One ; 16(5): e0251861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33999968

RESUMO

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.


Assuntos
Anticorpos Antiprotozoários/isolamento & purificação , Infecções por HIV/genética , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Proteínas Recombinantes/isolamento & purificação , Testes de Aglutinação , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Coinfecção/diagnóstico , Coinfecção/genética , Coinfecção/parasitologia , Ensaio de Imunoadsorção Enzimática , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/parasitologia , Infecções por HIV/virologia , Humanos , Leishmania infantum/genética , Leishmania infantum/patogenicidade , Leishmaniose Visceral/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/virologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/genética
11.
Hippocampus ; 31(7): 790-814, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33452843

RESUMO

The extinction of contextual fear is commonly an essential requirement for successful exposure therapy for fear disorders. However, experimental work on extinction of contextual fear is limited, and there little or no directly relevant theoretical work. Here, we extend BACON, a neurocomputational model of context fear conditioning that provides plausible explanations for a number of aspects of context fear conditioning, to deal with extinction (calling the model BaconX). In this model, contextual representations are formed in the hippocampus and association of fear to them occurs in the amygdala. Representation creation, conditionability, and development of between-session extinction are controlled by degree of confidence (assessed by the Bayesian weight of evidence) that an active contextual representation is in fact that of the current context (i.e., is "valid"). The model predicts that: (1) extinction which persists between sessions will occur only if at a sessions end there is high confidence that the active representation is valid. It follows that the shorter the context placement-to-US (shock) interval ("PSI") and the less is therefore learned about context, the longer extinction sessions must be for enduring extinction to occur, while too short PSIs will preclude successful extinction. (2) Short-PSI deficits can be rescued by contextual exposure even after conditioning has occurred. (3) Learning to discriminate well between a conditioned and similar safe context requires representations of each to form, which may not occur if PSI was too short. (4) Extinction-causing inhibition must be applied downstream of the conditioning locus for reasonable generalization properties to be generated. (5) Context change tends to cause return of extinguished contextual fear. (6). Extinction carried out in the conditioning context generalizes better than extinction executed in contexts to which fear has generalized (as done in exposure therapy). (7) BaconX suggests novel approaches to exposure therapy.


Assuntos
Condicionamento Clássico , Extinção Psicológica , Tonsila do Cerebelo/fisiologia , Teorema de Bayes , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Hipocampo/fisiologia
12.
Foot Ankle Orthop ; 6(3): 24730114211027115, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35097463

RESUMO

BACKGROUND: Midfoot arthrodesis has long been successfully included in the treatment paradigm for a variety of pathologic foot conditions. A concern with midfoot arthrodesis is the rate of nonunion, which historically has been reported between 5% and 10%. Plantar plating has also been noted to be more biomechanically stable when compared to traditional dorsal plating in previous studies. Practical advantages of plantar plating include less dorsal skin irritation and the ability to correct flatfoot deformity from the same medial incision. The purpose of this study is to report the arthrodesis rate, the success of deformity correction, and the complications associated with plantar-based implant placement for arthrodesis of the medial column. METHODS: A retrospective review was undertaken of all consecutive patients between 2012 and 2019 that underwent midfoot arthrodesis with plantar-positioned implants. Radiographic outcomes and complications are reported on 62 patients who underwent midfoot arthrodesis as part of a correction for hallux valgus deformity, flatfoot deformity, degenerative arthritis, Lisfranc injury, or Charcot neuroarthropathy correction. RESULTS: Statistically significant improvement was seen in the lateral talus-first metatarsal angle (Meary angle) and medial arch sag angle for patients treated for flatfoot deformity correction. In patients treated for hallux valgus deformity, there was a reduction in the intermetatarsal angle from 15.4 to 6.8 degrees. The overall nonunion rate was 6.45% in all patients. The rate of nonunion was higher at the NC joint compared to the TMT joint and with compression claw plates. One symptomatic nonunion required revision surgery (1.7%). There were no nonunions when excluding neuroarthropathy patients and smokers. The odds ratio (OR) for nonunion in patients with neuroarthropathy was 6.05 (P < .05), and in active smokers the OR was 2.33 (P < .05). CONCLUSION: Plates placed on the plantar bone surface for midfoot arthrodesis achieved and maintained deformity correction with rare instances of symptomatic hardware for a variety of orthopedic conditions. An overall clinical and radiographic union rate of 94% was achieved. The radiographic union rate improved to 100% when excluding both neuroarthropathy patients and smokers. The incidence of nonunion was higher in smokers, neuroarthropathy patients, naviculocuneiform joint fusions, use of compression claw plates, and when attempting to fuse multiple joints. Incisional healing complications were rarely seen other than in active smokers. LEVEL OF EVIDENCE: Level IV, case series.

13.
Prog Neurobiol ; 199: 101961, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33242572

RESUMO

We propose that a major contribution of juvenile and adult hippocampal neurogenesis is to allow behavioral experience to sculpt dentate gyrus connectivity such that sensory attributes that are relevant to the animal's environment are more strongly represented. This "specialized" dentate is then able to store a larger number of discriminable memory representations. Our hypothesis builds on accumulating evidence that neurogenesis declines to low levels prior to adulthood in many species. Rather than being necessary for ongoing hippocampal function, as several current theories posit, we argue that neurogenesis has primarily a prospective function, in that it allows experience to shape hippocampal circuits and optimize them for future learning in the particular environment in which the animal lives. Using an anatomically-based simulation of the hippocampus (BACON), we demonstrate that environmental sculpting of this kind would reduce overlap among hippocampal memory representations and provide representation cells with more information about an animal's current situation; consequently, it would allow more memories to be stored and accurately recalled without significant interference. We describe several new, testable predictions generated by the sculpting hypothesis and evaluate the hypothesis with respect to existing evidence. We argue that the sculpting hypothesis provides a strong rationale for why juvenile and adult neurogenesis occurs specifically in the dentate gyrus and why it declines significantly prior to adulthood.


Assuntos
Hipocampo , Neurogênese , Envelhecimento , Animais , Aprendizagem , Estudos Prospectivos
14.
Heliyon ; 6(10): e05158, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33083615

RESUMO

Red osier dogwood (ROD) (Cornus stolonifer) is a popular ornamental shrub in most parts of North America. It has a record of ethnopharmacological uses by native North Americans. With increasing awareness about the health benefits of natural antioxidants, efforts are needed to develop methods for producing plant-based antioxidants as sources of nutraceuticals or functional food ingredients. This study aimed at establishing an optimum temperature for hydrothermal extraction of phenolic compounds from the leaves and stems of ROD. Spray-dried extracts obtained from hydrothermal extraction at four different temperatures, as well as their raw materials and spent residue were analyzed for moisture content and water activity. The samples were extracted with organic solvent and their total phenolic content, phenolic composition and antioxidant activity were also determined. Moisture content was below 10% and the water activity was below 0.6 inclusive, which are recommended for storing dry plant products. Glucogallic acid, ellagic acid, rutin, quercetin 3-O-malonylglucoside and quercetin were the phenolic compounds identified in all the samples. Rutin was the predominant compound. As expected, all the spray-dried extracts had higher phenolic content and antioxidant activity than the raw materials and spent materials. Among the temperatures studied, 98 °C was the most effective in extracting the phenolic compounds. The spray-dried extracts may find application in high-value antioxidant-rich products such as functional food ingredients and nutraceuticals. The spent materials retained a considerable amount of phenolic antioxidants and can therefore be useful in preparing antioxidant-rich animal feed.

15.
Childs Nerv Syst ; 36(12): 2913-2918, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32734401

RESUMO

BACKGROUND AND AIM: Cleidocranial dysplasia is a rare disorder of skeletal development that mainly promotes, among other malformations, inadequate development of clavicles and failure in cranial closure. In this affection, the role of neurosurgery in addressing cranial defects is rarely discussed. MATERIAL AND METHODS: We conducted an extensive review of the literature using the PubMed database, giving a greater focus to publications in the field of neurosurgery. Additionally, we report a case of a 2-year-old female child with cleidocranial dysplasia. RESULTS: In our review, we encountered several cases of orthodontic implications but a few cases on cranial defect approach. CONCLUSION: The articles present literature that is unanimous on the recommendation of expectant conduct in children since the cranial block can occur spontaneously, even if the delayed form. In our approach, we opted for an expected strategy concerning the cranial defect, using a helmet made for brain protection. We also made the referral for multidisciplinary monitoring of pediatrics, neuropediatrics, ophthalmology, dentistry, and orthopedics.


Assuntos
Displasia Cleidocraniana , Pré-Escolar , Displasia Cleidocraniana/diagnóstico por imagem , Feminino , Dispositivos de Proteção da Cabeça , Humanos , Crânio
16.
PLoS Negl Trop Dis ; 14(7): e0008488, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32716931

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a major neglected disease, potentially fatal, whose control is still impaired by inefficient and/or expensive treatment and diagnostic methods. The most promising approach for VL diagnosis uses serological assays with recombinant proteins, since they are more efficient and easier to perform. Tests developed for the human form of the disease, however, have not been shown to be efficient for its diagnosis in the canine host, the major reservoir for the American VL. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a systematic approach aimed at the production of a new chimeric protein potentially able to be used for both human and canine VL diagnosis and based both on in silico gene design and experimental data. Starting from the previous identification of Leishmania infantum recombinant antigens efficient for the diagnosis of either human or canine VL, three of the best performing antigens were selected (Lci2, Lci3 and Lci12). After a preliminary evaluation validating the chimeric approach, DNA fragments encoding predicted antigenic regions from each protein, enriched with repeats, were joined in various combinations to generate a total of seventeen chimeric genes optimized for prokaryotic expression. These were assessed for optimal expression and purification yield, with four chimeric proteins being efficiently produced. Their diagnostic potential was then evaluated through ELISA assays with sera from VL afflicted humans and dogs. After two rounds of gene design, the results showed high levels of sensitivity for the best chimeric protein, named Q5, in humans (82%) and dogs (100%) with 100% specificity in comparison with healthy controls. A single non-specific reaction was seen with serum from individuals with tegumentary leishmaniasis. CONCLUSION: The newly described chimeric protein is potentially useful for the detection of both humans and dogs afflicted with VL, with its use in rapid tests necessary for validation as a new diagnostic tool.


Assuntos
Doenças do Cão/diagnóstico , Leishmaniose Visceral/veterinária , Testes Sorológicos/veterinária , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/química , Doenças do Cão/sangue , Cães , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Humanos , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Proteínas de Protozoários/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Transcriptoma
17.
Curr Biol ; 30(12): 2300-2311.e6, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32442458

RESUMO

The context in which sudden fearful events occur can be poorly encoded into memory. Yet, the consequences of the resulting context-impoverished memories remain unknown. We demonstrate that restricting the time available for context encoding during contextual fear conditioning causes maladaptively overgeneralized and inextinguishable fear. However, post-conditioning context exposure enables further context encoding through hippocampal reconsolidation-dependent memory updating. Updating in the conditioning context alleviates overgeneralization and restores capacity for extinction. However, updating in a similar safe context erroneously shifts fear from the dangerous to the safe context. We argue that these phenomena can be explained by uncertainty about where events occurred. Moreover, we show that a hippocampal-neocortical neurocomputational model based on this assumption successfully simulates and explains our observations. These findings reveal that context-impoverished memories are maladaptive and can be improved or distorted after recall, with implications for basic memory theory, memory distortion, and treatment of disorders like post-traumatic stress disorder.


Assuntos
Extinção Psicológica/fisiologia , Rememoração Mental/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
J Microbiol Methods ; 172: 105903, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32229265

RESUMO

The Yersinia pestis capsular antigen F1 is widely used in plague laboratory diagnosis. Here, we describe the production of an F1 recombinant protein within reduced time and biosafety requirements. Its evaluation in hemagglutination tests indicated that the recombinant F1 can replace the conventional F1 protein for plague diagnosis.


Assuntos
Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Custos e Análise de Custo , Peste/diagnóstico , Peste/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Testes de Hemaglutinação/métodos , Masculino , Coelhos , Proteínas Recombinantes/imunologia , Fatores de Tempo
19.
J Orthop ; 19: 31-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021032

RESUMO

BACKGROUND: Arthroscopic suprascapular nerve release has yielded good results previously. However, comprehensive literature is still lacking. PURPOSE: This study assessed results of suprascapular nerve release in patients with intractable shoulder pain with confirmed suprascapular neuropathy. METHODS: Retrospectively reviewed patients undergoing suprascapular nerve release. Patients were evaluated with VAS scores and supraspinatus/infraspinatus strength. RESULTS: 112 patients were included showing reduction in VAS pain scores from the initial visit to final follow up. Additionally, improvement in both supra/infraspinatus strength occurred. There were no major complications. CONCLUSION: This series demonstrates improvement in pain and strength following suprascapular nerve release with limited risk. LEVEL OF EVIDENCE: IV.

20.
Plant Foods Hum Nutr ; 75(1): 41-47, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31788720

RESUMO

Brewers' spent grain (BSG) is the major by-product of the brewing industry, with great potential as a functional ingredient due to its bioactive compounds. Thus, BSG could be suitable for improving the low nutritional quality of wheat-based snacks highly consumed by young people. The objective of this study was to substitute wheat flour with BSG (0, 10, 20, and 30%) for cookies elaboration, and evaluate the dough rheology, phenolic acids, antioxidant capacity, arabinoxylans content and proximate composition of the cookies Protein content and bioactive compounds (ferulic and p-coumaric acids, water unextractable arabinoxylans) of cookies significantly (p < 0.05) increased with the substitution level. In comparison to the wheat-alone cookies, the 20% BSG-containing cookies showed a lower hydrolysis and glycemic index (GI), and less total starch. The low cost, protein-rich BSG with antioxidant capacity improves the nutritional quality of cookies and may confer health benefits beyond basic nutrition.


Assuntos
Antioxidantes , Índice Glicêmico , Grão Comestível , Farinha , Valor Nutritivo
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