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1.
Cell ; 170(2): 273-283.e12, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28708997

RESUMO

The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.


Assuntos
Vacinas Virais/administração & dosagem , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/fisiologia , Aedes/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Células Sanguíneas/virologia , Embrião de Mamíferos/virologia , Feminino , Feto/virologia , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Organismos Livres de Patógenos Específicos , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/virologia
2.
EMBO Rep ; 24(8): e57306, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37334900

RESUMO

Skeletal muscle plays a key role in systemic energy homeostasis besides its contractile function, but what links these functions is poorly defined. Protein Arginine Methyl Transferase 5 (PRMT5) is a well-known oncoprotein but also expressed in healthy tissues with unclear physiological functions. As adult muscles express high levels of Prmt5, we generated skeletal muscle-specific Prmt5 knockout (Prmt5MKO ) mice. We observe reduced muscle mass, oxidative capacity, force production, and exercise performance in Prmt5MKO mice. The motor deficiency is associated with scarce lipid droplets in myofibers due to defects in lipid biosynthesis and accelerated degradation. Specifically, PRMT5 deletion reduces dimethylation and stability of Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a), a master regulator of de novo lipogenesis. Moreover, Prmt5MKO impairs the repressive H4R3 symmetric dimethylation at the Pnpla2 promoter, elevating the level of its encoded protein ATGL, the rate-limiting enzyme catalyzing lipolysis. Accordingly, skeletal muscle-specific double knockout of Pnpla2 and Prmt5 normalizes muscle mass and function. Together, our findings delineate a physiological function of PRMT5 in linking lipid metabolism to contractile function of myofibers.


Assuntos
Proteína-Arginina N-Metiltransferases , Transferases , Animais , Camundongos , Arginina/metabolismo , Metabolismo dos Lipídeos/genética , Músculo Esquelético/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Transferases/metabolismo
3.
Ann Surg Oncol ; 31(7): 4349-4360, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538822

RESUMO

BACKGROUND: Oncology outreach is a common strategy for increasing rural access to cancer care, where traveling oncologists commute across healthcare settings to extend specialized care. Examining the extent to which physician outreach is associated with timely treatment for rural patients is critical for informing outreach strategies. METHODS: We identified a 100% fee-for-service sample of incident breast cancer patients from 2015 to 2020 Medicare claims and apportioned them into surgery and adjuvant therapy cohorts based on treatment history. We defined an outreach visit as the provision of care by a traveling oncologist at a clinic outside of their primary hospital service area. We used hierarchical logistic regression to examine the associations between patient receipt of preoperative care at an outreach visit (preoperative outreach) and > 60-day surgical delay, and patient receipt of postoperative care at an outreach visit (postoperative outreach) and > 60-day adjuvant delay. RESULTS: We identified 30,337 rural-residing patients who received breast cancer surgery, of whom 4071 (13.4%) experienced surgical delay. Among surgical patients, 14,501 received adjuvant therapy, of whom 2943 (20.3%) experienced adjuvant delay. In adjusted analysis, we found that patient receipt of preoperative outreach was associated with reduced odds of surgical delay (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.91); however, we found no association between patient receipt of postoperative outreach and adjuvant delay (OR 1.04, 95% CI 0.85-1.25). CONCLUSIONS: Our findings indicate that preoperative outreach is protective against surgical delay. The traveling oncologists who enable such outreach may play an integral role in catalyzing the coordination and timeliness of patient-centered care.


Assuntos
Neoplasias da Mama , Acessibilidade aos Serviços de Saúde , Medicare , População Rural , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/terapia , Idoso , População Rural/estatística & dados numéricos , Estados Unidos , Medicare/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Seguimentos , Idoso de 80 Anos ou mais , Prognóstico , Planos de Pagamento por Serviço Prestado , Mastectomia
4.
Cochrane Database Syst Rev ; 7: CD014146, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041371

RESUMO

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effects of exercise alone or exercise plus education compared with inactive control or education alone to prevent non-specific LBP.


Assuntos
Terapia por Exercício , Dor Lombar , Dor Lombar/prevenção & controle , Dor Lombar/terapia , Humanos , Terapia por Exercício/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Educação de Pacientes como Assunto/métodos , Exercício Físico
5.
BMC Musculoskelet Disord ; 25(1): 593, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068385

RESUMO

BACKGROUND: The current literature supports the effectiveness of exercise, education, and self-management interventions for the long-term management of persistent low back pain. However, there is significant uncertainty about the implementation of interventions related to barriers, facilitators, and patient's preferences. This study will evaluate the Back to Living Well program implementation from a participant and organizational perspective. More specifically we address the following objectives: 1) identify program barriers and facilitators from participants' perspectives, 2) identify factors related to program, personal and contextual factors that contribute to negative and positive outcomes, and outcome trajectories, 3) identify factors influencing participants' selection of an in-person or e-health program, and 4) evaluate program specific barriers and facilitators from the organization and care delivery perspectives. METHODS: This study will utilize a mixed-method convergent design including a longitudinal cohort strand and a longitudinal qualitative interview strand. The RE-AIM framework will be used to assess program implementation. Participants (n = 90, 1:1: in person or virtual) who choose to register in the program as well as staff (n = 10 to 15) involved in the delivery of the program will be invited to participate. Participants will participate in a 12-week physical activity, education, and self-management program. Implementation outcomes will be measured at 3-, 6-, 12-months, and six months after the end of the follow-ups. Interview scripts and directed content analysis will be constructed based on the Theoretical Domains Framework and the Neuromatrix Model of Pain, Theoretical Domains Framework. Staff interviews will be constructed and analyzed using the Consolidated Framework for Implementation Research. Participants will also complete pain, disability, quality of life and psychological questionnaires, wear an activity tracker at all time points, and complete weekly pain and activity limitation questions using a mobile application. DISCUSSION: The study results will provide evidence to inform potential future implementation of the program. An effective, appropriately targeted, and well implemented exercise program for the long-term management (i.e., tertiary prevention) of LBP could minimize the burden of the condition on patients, the health care system and society. TRIAL REGISTRATION: ClinicalTrials.gov NCT05929846. This (Registration Date: July 3 2023) study has been approved by the Hamilton Integrated Research Ethics Board Project ID#15,354.


Assuntos
Dor Lombar , Prevenção Terciária , Humanos , Dor Lombar/terapia , Dor Lombar/prevenção & controle , Prevenção Terciária/métodos , Terapia por Exercício/métodos , Educação de Pacientes como Assunto/métodos , Autogestão/métodos , Serviços de Saúde Comunitária/métodos , Estudos Longitudinais , Avaliação de Programas e Projetos de Saúde , Feminino , Qualidade de Vida , Adulto , Medição da Dor
6.
Am J Drug Alcohol Abuse ; : 1-11, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833614

RESUMO

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

7.
Angew Chem Int Ed Engl ; 63(17): e202400712, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38439710

RESUMO

By combining bioimaging and photodynamic therapy (PDT), it is possible to treat cancer through a theranostic approach with targeted action for minimum invasiveness and side effects. Thermally activated delayed fluorescence (TADF) probes have gained recent interest in theranostics due to their ability to generate singlet oxygen (1O2) while providing delayed emission that can be used in time-gated imaging. However, it is still challenging to design systems that simultaneously show (1) high contrast for imaging, (2) low dark toxicity but high phototoxicity and (3) tunable biological uptake. Here, we circumvent shortcomings of TADF systems by designing block copolymers and their corresponding semiconducting polymer dots (Pdots) that encapsulate a TADF dye in the core and expose an additional boron-dipyrromethene (BODIPY) oxygen sensitizer in the corona. This architecture provides orange-red luminescent particles (ΦPL up to 18 %) that can efficiently promote PDT (1O2 QY=42 %) of HeLa cells with very low photosensitizer loading (IC50 ~0.05-0.13 µg/mL after 30 min). Additionally, we design Pdots with tunable cellular uptake but similar PDT efficiencies using either polyethylene glycol or guanidinium-based coronas. Finally, we demonstrate that these Pdots can be used for time-gated imaging to effectively filter out background fluorescence from biological samples and improve image contrast.


Assuntos
Fotoquimioterapia , Humanos , Células HeLa , Fluorescência , Linhagem Celular Tumoral , Polímeros , Fármacos Fotossensibilizantes/farmacologia , Corantes Fluorescentes
8.
Exp Brain Res ; 241(4): 1173-1183, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36912948

RESUMO

Impairments in several domains of cognitive functions are observed in people with Type 2 Diabetes Mellitus (T2DM), often accompanied by low Brain-derived neurotrophic factor (BDNF) concentrations. Although aerobic and resistance exercise enhances cognitive functions and raises BDNF concentrations in several populations, it remained uncertain in T2DM subjects. This study compared the effects of a single bout of aerobic (AER, 40 min of treadmill walk at 90-95% of the maximum walk speed) or resistance (RES, 3 × 10 repetitions in eight exercises at 70% of 10-RM) exercise on specific cognitive domain performance and plasma BDNF concentrations of physically active T2DM subjects. Eleven T2DM subjects (9 women/2 men; 63 ± 7 years) performed two counterbalanced trials on non-consecutive days. Stroop Color and Word (SCW) task [assessing the attention (congruent condition) and inhibitory control (incongruent condition)], Visual response time (assessing the response time), and blood collection (for plasma BDNF concentrations) were performed pre and post-exercise sessions. With distinct magnitude, both AER and RES improved the incongruent-SCW (d = - 0.26 vs. - 0.43 in AER and RES, respectively; p < 0.05), RT(best) (d = - 0.31 vs. - 0.52, p < 0.05), and RT(1-5) (d = - 0.64 vs. - 0.21, p < 0.05). The congruent-SCW and RT(6-10) were not statistically different. Plasma BDNF concentrations were elevated 11% in AER (d = 0.30) but decreased by 15% in RES (d = - 0.43). A single session of aerobic or resistance exercise similarly improved the inhibitory control and response time of physically active T2DM subjects. Nevertheless, aerobic and resistance exercise sessions induced an opposite clinical effect in plasma BDNF concentrations.


Assuntos
Diabetes Mellitus Tipo 2 , Treinamento Resistido , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Diabetes Mellitus Tipo 2/terapia , Fator Neurotrófico Derivado do Encéfalo , Tempo de Reação , Exercício Físico/fisiologia
9.
J Nanobiotechnology ; 21(1): 166, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231443

RESUMO

BACKGROUND: The biogenic synthesis of metallic nanoparticles is a green alternative that reduces the toxicity of this nanomaterials and may enable a synergy between the metallic core and the biomolecules employed in the process enhancing biological activity. The aim of this study was to synthesize biogenic titanium nanoparticles using the filtrate of the fungus Trichoderma harzianum as a stabilizing agent, to obtain a potential biological activity against phytopathogens and mainly stimulate the growth of T. harzianum, enhancing its efficacy for biological control. RESULTS: The synthesis was successful and reproductive structures remained in the suspension, showing faster and larger mycelial growth compared to commercial T. harzianum and filtrate. The nanoparticles with residual T. harzianum growth showed inhibitory potential against Sclerotinia sclerotiorum mycelial growth and the formation of new resistant structures. A great chitinolytic activity of the nanoparticles was observed in comparison with T. harzianum. In regard to toxicity evaluation, an absence of cytotoxicity and a protective effect of the nanoparticles was observed through MTT and Trypan blue assay. No genotoxicity was observed on V79-4 and 3T3 cell lines while HaCat showed higher sensitivity. Microorganisms of agricultural importance were not affected by the exposure to the nanoparticles, however a decrease in the number of nitrogen cycling bacteria was observed. In regard to phytotoxicity, the nanoparticles did not cause morphological and biochemical changes on soybean plants. CONCLUSION: The production of biogenic nanoparticles was an essential factor in stimulating or maintaining structures that are important for biological control, showing that this may be an essential strategy to stimulate the growth of biocontrol organisms to promote more sustainable agriculture.


Assuntos
Hypocreales , Nanopartículas Metálicas , Trichoderma , Trichoderma/química , Trichoderma/metabolismo , Titânio/farmacologia , Titânio/metabolismo , Nanopartículas Metálicas/toxicidade
10.
BMC Musculoskelet Disord ; 24(1): 277, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038146

RESUMO

BACKGROUND: Although clinical practice guidelines recommend pain education as the first-line option for the management of chronic musculoskeletal pain, there is a lack of pain education programmes in healthcare. Thus, digital health programmes can be an effective tool for implementing pain education strategies for public health. This trial will aim to analyse the implementation and effectiveness outcomes of three online pain science education strategies in the Brazilian public health system (SUS) for individuals with chronic musculoskeletal pain. METHODS: We will conduct a hybrid type III effectiveness-implementation randomised controlled trial with economic evaluation. We will include adult individuals with chronic musculoskeletal pain, recruited from primary healthcare in the city of Guarapuava, Brazil. Individuals will be randomised to three implementation groups receiving a pain science education intervention (EducaDor) but delivered in different modalities: group 1) synchronous online; group 2) asynchronous videos; and group 3) interactive e-book only. Implementation outcomes will include acceptability, appropriateness, feasibility, adoption, fidelity, penetration, sustainability, and costs. We will also assess effectiveness outcomes, such as pain, function, quality of life, sleep, self-efficacy, and adverse effects. Cost-effectiveness and cost-utility analyses will be conducted from the SUS and societal perspectives. The evaluations will be done at baseline, post-intervention (10 weeks), and 6 months. DISCUSSION: This study will develop and implement a collaborative intervention model involving primary healthcare professionals, secondary-level healthcare providers, and patients to enhance self-management of chronic pain. In addition to promoting better pain management, this study will also contribute to the field of implementation science in public health by generating important insights and recommendations for future interventions. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05302180; 03/29/2022).


Assuntos
Dor Crônica , Dor Musculoesquelética , Adulto , Humanos , Dor Crônica/diagnóstico , Dor Crônica/terapia , Análise Custo-Benefício , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/terapia , Brasil , Qualidade de Vida , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
BMC Musculoskelet Disord ; 24(1): 783, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789304

RESUMO

BACKGROUND: Telehealth has emerged as an alternative model for treatment delivery and has become an important component of health service delivery. However, there is inconsistency in the use of terminologies and a lack of research priorities in telehealth in musculoskeletal pain. The purpose of this international, multidisciplinary expert panel assembled in a modified three-round e-Delphi survey is to achieve a consensus on research priorities and for the standard terminology for musculoskeletal pain telehealth practice. METHODS: In this international modified e-Delphi survey, we invited an expert panel consisting of researchers, clinicians, consumer representatives, industry partners, healthcare managers, and policymakers to participate in a three-round e-Delphi. Expert panels were identified through the Expertscape website, PubMed database, social media, and a snowball approach. In Round 1, potential research priorities and terminologies were presented to panel members. Panel members rated the agreement of each research priority on a 5-point Likert scale and an 11-point numerical scale, and each terminology on a 5-point Likert scale for the "telehealth in musculoskeletal pain " field over rounds. At least 80% of the panel members were required to agree to be deemed a consensus. We analyzed the data descriptively and assessed the stability of the results using the Wilcoxon matched-pairs signed rank test. RESULTS: We performed an international e-Delphi survey from February to August 2022. Of 694 invited people, 160 panel members participated in the first round, 133 in the second round (83% retention), and 134 in the third round (84% retention). Most of the panel members were researchers 76 (47%), clinicians 57 (36%), and consumer representatives 9 (6%) of both genders especially from Brazil 31 (19%), India 22 (14%), and Australia 19 (12%) in the first round. The panel identified fourteen telehealth research priorities spanned topics including the development of strategies using information and communication technology, telehealth implementation services, the effectiveness and cost-effectiveness of telehealth interventions, equity of telehealth interventions, qualitative research and eHealth literacy in musculoskeletal pain conditions from an initial list of 20 research priorities. The consensus was reached for "digital health" and "telehealth" as standard terminologies from an initial list of 37 terminologies. CONCLUSION: An international, multidisciplinary expert consensus recommends that future research should consider the 14 research priorities for telehealth musculoskeletal pain reached. Additionally, the terms digital health and telehealth as the most appropriate terminologies to be used in musculoskeletal telehealth research. REGISTER: Open Science Framework ( https://osf.io/tqmz2/ ).


Assuntos
Pesquisa Biomédica , Dor Musculoesquelética , Telemedicina , Humanos , Masculino , Feminino , Consenso , Técnica Delphi , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/terapia
12.
Environ Res ; 215(Pt 1): 114147, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36063907

RESUMO

Mercury (Hg) toxicity in soils depends on Hg species and other physical and chemical attributes, as selenium (Se) hotspots in soils, particularly relevant in Amazonian soils. The study of Hg species and their relations in representative locations of the Amazon rainforest biome is critical for assessing the potential risks of Hg in this environment. This work aimed to determine the concentration of total Hg and its species (Hg0, Hg22+ and Hg2+), and to correlate Hgtotal concentration with total elemental composition, magnetic susceptibility, and physicochemical attributes of Amazon soils. Nine sites in the Amazon rainforest biome, Brazil, were selected and analyzed for their chemical, physical, and mineralogical attributes. The clay fraction of the studied Amazon soils is dominated by kaolinite, goethite, hematite, gibbsite, and quartz. Mica was also found in soils from the States of Acre and Amazonas. Hgtotal ranged from 21.5 to 208 µg kg-1 (median = 104 µg kg-1), and the concentrations did not exceed the threshold value established for Brazilian soils (500 µg kg-1). The Hg2+ was notably the predominant species. Its occurrence and concentration were correlated with the landscape position and soil attributes. Hgtotal was moderately and positively correlated with TiO2, clay, and Se. The findings showed that geographic location, geological formation, and pedological differences influence the heterogeneity and distribution of Hgtotal in the studied soil classes. Thus, a detailed characterization and knowledgment of the soil classes is very important to clarify the complex behavior of this metal in the Amazon rainforest biome.


Assuntos
Mercúrio , Selênio , Poluentes do Solo , Brasil , Argila , Ecossistema , Monitoramento Ambiental , Caulim , Mercúrio/análise , Quartzo , Floresta Úmida , Selênio/análise , Solo/química , Poluentes do Solo/análise
13.
Mol Ther ; 29(1): 132-148, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33068545

RESUMO

Duchenne muscular dystrophy (DMD) is caused by a mutation of the muscle membrane protein dystrophin and characterized by severe degeneration of myofibers, progressive muscle wasting, loss of mobility, and, ultimately, cardiorespiratory failure and premature death. Currently there is no cure for DMD. Herein, we report that skeletal muscle-specific knockout (KO) of the phosphatase and tensin homolog (Pten) gene in an animal model of DMD (mdx mice) alleviates myofiber degeneration and restores muscle function without increasing tumor incidence. Specifically, Pten KO normalizes myofiber size and prevents muscular atrophy, and it improves grip strength and exercise performance in mdx mice. Pten KO also reduces fibrosis and inflammation, and it ameliorates muscle pathology in mdx mice. Unbiased RNA sequencing reveals that Pten KO upregulates extracellular matrix and basement membrane components positively correlated with wound healing and suppresses negative regulators of wound healing and lipid biosynthesis, thus improving the integrity of muscle basement membrane at the ultrastructural level. Importantly, pharmacological inhibition of PTEN similarly ameliorates muscle pathology and improves muscle integrity and function in mdx mice. Our findings provide evidence that PTEN inhibition may represent a potential therapeutic strategy to restore muscle function in DMD.


Assuntos
Técnicas de Silenciamento de Genes , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , PTEN Fosfo-Hidrolase/genética , Regeneração/genética , Animais , Biomarcadores , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/ultraestrutura , Distrofia Muscular de Duchenne/fisiopatologia
14.
J Am Soc Nephrol ; 32(4): 994-1004, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33658284

RESUMO

BACKGROUND: Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. METHODS: Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. RESULTS: An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. CONCLUSIONS: Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

15.
J Strength Cond Res ; 36(2): 461-468, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855926

RESUMO

ABSTRACT: Campos, BT, Penna, EM, Rodrigues, JGS, Mendes, TT, Maia-Lima, A, Nakamura, FY, Vieira, ÉLM, Wanner, SP, and Prado, LS. Influence of mental fatigue on physical performance, and physiological and perceptual responses of judokas submitted to the Special Judo Fitness Test. J Strength Cond Res 36(2): 461-468, 2022-Mentally fatigued athletes present impaired aerobic performance, strength endurance, and manual dexterity, despite no changes in anaerobic performance and maximal muscle strength and power. Noteworthy, the effect of mental fatigue on physical performance during high-intensity intermittent tests that require specific motor skills of fighting sports has not been investigated. Therefore, this study aimed to verify whether mental fatigue influences performance and physiological and perceptual responses of judokas subjected to a high-intensity intermittent test designed specifically and validated for judo. Each judoka performed 2 experimental trials-a control trial one and the other one after the induction of mental fatigue. These trials were scheduled in a random and balanced order. In both trials, lactate, glucose, and cortisol concentrations, the heart rate variability, and perceptual variables were collected after the initial treatment and after the Special Judo Fitness Test (SJFT). The initial treatment consisted of a 30-minute cognitive demanding task (Stroop Color test) or watching a movie (control) and was followed by the SJFT. The Stroop Color test increased the perceptions of mental fatigue and effort, without affecting motivation for subsequent testing. Unexpectedly, mentally fatigued athletes did not show reduced performance during the SJFT. Regarding the physiological variables, no significant differences were identified between the 2 experimental conditions. We conclude that physical performance measured during a specific test for judokas is not impaired by a previous 30-minute cognitive task that causes mental fatigue. In addition, this cognitive task did not influence the physiological changes induced by the specific physical test.


Assuntos
Desempenho Atlético , Artes Marciais , Teste de Esforço , Humanos , Fadiga Mental , Aptidão Física , Desempenho Físico Funcional
16.
Angew Chem Int Ed Engl ; 61(4): e202114586, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34826183

RESUMO

The discovery of metallic conductivity in polyacetylene [-HC=CH-]n upon doping represents a landmark achievement. However, the insolubility of polyacetylene and a dearth of methods for its chemical modification have limited its widespread use. Here, we employ a ring-opening metathesis polymerization (ROMP) protocol to prepare functionalized polyacetylenes (fPAs) bearing: (1) electron-deficient boryl (-BR2 ) and phosphoryl (-P(O)R2 ) side chains; (2) electron-donating amino (-NR2 ) groups, and (3) ring-fused 1,2,3-triazolium units via strain-promoted Click chemistry. These functional groups render most of the fPAs soluble and can lead to intense light absorption across the visible to near-IR region. Also, the presence of redox-active boryl and amino groups leads to opposing near-IR optical responses upon (electro)chemical reduction or oxidation. Some of the resulting fPAs show greatly enhanced air stability when compared to known polyacetylenes. Lastly, these fPAs can be cross-linked to yield network materials with the full retention of optical properties.

17.
Opt Express ; 29(13): 20136-20149, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34266109

RESUMO

Free-space optics (FSO) convey an enormous potential for ultra-high-capacity seamless fiber-wireless transmission in 5G and beyond communication systems. However, for its practical exploitation in future deployments, FSO still requires the development of very high-precision and robust optical beam alignment. In this paper, we propose two different methods to achieve tight, precise alignment between a pair of FSO transceivers, using a gimbal-based setup. For scenarios where there is no information about the system, a black-box artificial intelligence (AI)-based method resorting to particle swarm optimization (PSO) is presented, enabling to autonomously align the system with a success rate above 96%, converging from a blind starting position. Alternatively, for scenarios with partial information about the FSO system, we propose a tailored custom algorithm, with a success rate of 92%, but with a ∼4 × reduction on the alignment time. The automatic alignment is then validated in a 5G-like fiber-FSO scenario, transmitting a 16 × 400 MHz signal and achieving a maximum bit-rate of 30 Gbps. Moreover, we propose the implementation of a fail-safe mechanism with a backup FSO receiver, thereby providing an extra degree of robustness towards temporary events of strong degradation on the FSO channel or line-of-sight (LOS) interruption.

18.
Environ Monit Assess ; 193(4): 203, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751261

RESUMO

On November 5, 2015, the Fundão dam collapsed and released > 60 million m3 of iron-rich mining sediments into the Doce river basin, covering >1000 ha of floodplain soils across ~80 km from the rupture. The characterization of alluvial mud covering and/or mixed with native soil is a priority for successful environmental rehabilitation. Portable X-ray fluorescence (pXRF) spectrometry was used to (1) assess the elemental composition of native soils and alluvial mud across impacted riparian areas; and 2) predict fertility properties of the mud and soils that are crucial for environmental rehabilitation and vegetation establishment (e.g., pH, available macro and micronutrients, cation exchange capacity, organic matter). Native soils and alluvial mud were sampled across impacted areas and analyzed via pXRF and conventional laboratory methods. Random forest (RF) regression was used to predict fertility properties using pXRF data for pooled soil and alluvial mud samples. Mud and native surrounding soils were clearly differentiated based on chemical properties determined via pXRF (mainly SiO2, Al2O3, Fe2O3, TiO2, and MnO). The pXRF data and RF models successfully predicted pH for pooled samples (R2 = 0.80). Moderate predictions were obtained for soil organic matter (R2 = 0.53) and cation exchange capacity (R2 = 0.54). Considering the extent of impacted area and efforts required for successful environmental rehabilitation, the pXRF spectrometer showed great potential for screening impacted areas. It can assess total elemental composition, differentiate alluvial mud from native soils, and reasonably predict related fertility properties in pooled heterogeneous substrates (native soil + mud + river sediments).


Assuntos
Desastres , Poluentes do Solo , Brasil , Monitoramento Ambiental , Ferro , Dióxido de Silício , Solo , Poluentes do Solo/análise , Espectrometria por Raios X
19.
Exerc Sport Sci Rev ; 48(4): 163-169, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32658042

RESUMO

The prolonged impairment in muscle strength, power, and fatigue resistance after eccentric exercise has been ascribed to a plethora of mechanisms, including delayed muscle refueling and microvascular and mitochondrial dysfunction. This review explores the hypothesis that local heat therapy hastens functional recovery after strenuous eccentric exercise by facilitating glycogen resynthesis, reversing vascular derangements, augmenting mitochondrial function, and stimulating muscle protein synthesis.


Assuntos
Exercício Físico/fisiologia , Temperatura Alta/uso terapêutico , Músculo Esquelético/lesões , Mialgia/terapia , Adaptação Fisiológica , Animais , Glicogênio/biossíntese , Humanos , Microcirculação , Mitocôndrias Musculares/fisiologia , Fadiga Muscular/fisiologia , Proteínas Musculares/biossíntese , Força Muscular/fisiologia , Músculo Esquelético/irrigação sanguínea , Mialgia/etiologia
20.
Popul Health Metr ; 18(Suppl 1): 11, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32993681

RESUMO

BACKGROUND: Estimates of completeness of death registration are crucial to produce estimates of life tables and population projections and to estimate the burden of disease. They are an important step in assessing the quality of data. In the case of subnational data analysis in Brazil, it is important to consider spatial and temporal variation in the quality of mortality data. There are two main sources of data quality evaluation in Brazil, but there are few comparative studies and how they evolve over time. The aim of the paper is to compare and discuss alternative estimates of completeness of death registration, adult mortality (45q15) and life expectancy estimates produced by the National Statistics Office (IBGE), Institute for Health Metrics and Evaluation (IHME), and estimates presented in Queiroz et al. (2017) and Schmertmann and Gonzaga (2018), for 1980 and 2010. METHODS: We provide a descriptive and comparative analysis of aforementioned estimates from four (4) sources of estimates at subnational level (26 states and one Federal District) in Brazil from two different points in time. RESULTS: We found significant differences in estimates that affect both levels and trends of completeness of adult mortality in Brazil and states. IHME and Queiroz et al. (2017) estimates converge by 2010, but there are large differences when compared to estimates from the National Statistics Office (IBGE). Larger differences are observed for less developed states. We have showed that the quality of mortality data in Brazil has improved steadily overtime, but with large regional variations. However, we have observed that IBGE estimates show the lowest levels of completeness for the Northern of the country compared to other estimates. Choice of methods and approaches might lead to very unexpected results. CONCLUSION: We produced a detailed comparative analysis of estimates of completeness of death registration from different sources and discuss the main results and possible explanations for these differences. We have also showed that new improved methods are still needed to study adult mortality in less developed countries and at a subnational level. More comparative studies are important in order to improve quality of estimates in Brazil.


Assuntos
Coleta de Dados/normas , Atestado de Óbito , Expectativa de Vida/tendências , Mortalidade/tendências , Teorema de Bayes , Brasil/epidemiologia , Países em Desenvolvimento , Saúde Global , Humanos , Tábuas de Vida , Características de Residência , Análise Espaço-Temporal
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