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1.
Br J Sports Med ; 58(3): 144-153, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38216323

RESUMO

OBJECTIVE: To systematically map the coach education (CE) component of injury prevention programmes (IPPs) for youth field sports by identifying and synthesising the design, content and facilitation strategies used to address competency drivers and behaviour change. DESIGN: Scoping review. DATA SOURCES: PubMed, PsycInfo, EMBASE, CINAHL, SportDiscus and Google Scholar electronic databases were searched using keywords related to IPPs and youth field sports. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies of IPPs in youth field sports, that provided 'train-the-trainer' education to coaches as designated delivery agents. RESULTS: 20 studies from two field sports (soccer/football; n=17, Rugby Union; n=3) fulfilled the eligibility criteria. Eleven CE interventions occurred in the preseason and 18 occurred at one time-point (single day). Five studies cited use of a behavioural change theory or model in the design of their CE, most frequently the Health Action Process Approach model (n=5); and use of behavioural change techniques varied. Twelve of twenty studies (60%) reported some form of ongoing support to coaches following the CE primary intervention concurrent with IPP implementation. CONCLUSION: CE that occurs on 1 day (one time-point) is most popular for preparing coaches as delivery agents of IPPs in youth field sports. While recognising pragmatic barriers, more expansive in-service training, support and feedback may enhance the effective implementation of IPPs. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/FMHGD.


Assuntos
Traumatismos em Atletas , Futebol , Esportes Juvenis , Humanos , Adolescente , Traumatismos em Atletas/prevenção & controle , Futebol/lesões , Esportes Juvenis/lesões
2.
Prev Sci ; 24(Suppl 1): 50-60, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35947282

RESUMO

The rapid rise in opioid misuse, disorder, and opioid-involved deaths among older adolescents and young adults is an urgent public health problem. Prevention is a vital part of the nation's response to the opioid crisis, yet preventive interventions for those at risk for opioid misuse and opioid use disorder are scarce. In 2019, the National Institutes of Health (NIH) launched the Preventing Opioid Use Disorder in Older Adolescents and Young Adults cooperative as part of its broader Helping to End Addiction Long-term (HEAL) Initiative ( https://heal.nih.gov/ ). The HEAL Prevention Cooperative (HPC) includes ten research projects funded with the goal of developing effective prevention interventions across various settings (e.g., community, health care, juvenile justice, school) for older adolescent and young adults at risk for opioid misuse and opioid use disorder (OUD). An important component of the HPC is the inclusion of an economic evaluation by nine of these research projects that will provide information on the costs, cost-effectiveness, and sustainability of these interventions. The HPC economic evaluation is integrated into each research project's overall design with start-up costs and ongoing delivery costs collected prospectively using an activity-based costing approach. The primary objectives of the economic evaluation are to estimate the intervention implementation costs to providers, estimate the cost-effectiveness of each intervention for reducing opioid misuse initiation and escalation among youth, and use simulation modeling to estimate the budget impact of broader implementation of the interventions within the various settings over multiple years. The HPC offers an extraordinary opportunity to generate economic evidence for substance use prevention programming, providing policy makers and providers with critical information on the investments needed to start-up prevention interventions, as well as the cost-effectiveness of these interventions relative to alternatives. These data will help demonstrate the valuable role that prevention can play in combating the opioid crisis.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Opioides , Adolescente , Adulto Jovem , Humanos , Análise Custo-Benefício , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides
3.
FASEB J ; 35(9): e21752, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369602

RESUMO

Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1ß coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1ß [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1α4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.


Assuntos
Tecido Adiposo/metabolismo , Mitocôndrias/genética , Proteínas Nucleares/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fatores de Transcrição/genética , Envelhecimento/genética , Animais , Modelos Animais de Doenças , Metabolismo Energético/genética , Heterozigoto , Resistência à Insulina/genética , Masculino , Camundongos , Obesidade/genética , Termogênese/genética , Transcriptoma/genética
4.
Vet Anaesth Analg ; 49(6): 645-649, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36064498

RESUMO

OBJECTIVE: To describe some cardiorespiratory effects of an inspiratory-to-expiratory (IE) ratio of 1:1 compared with 1:3 in ventilated horses in dorsal recumbency. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of eight anesthetized horses, with 444 (330-485) kg body weight [median (range)]. METHODS: Horses were ventilated in dorsal recumbency with a tidal volume of 15 mL kg-1 and a respiratory rate of 8 breaths minute-1, and IE ratios of 1:1 (IE1:1) and 1:3 (IE1:3) in random order, each for 25 minutes after applying a recruitment maneuver. Spirometry, arterial blood gases and dobutamine requirements were recorded in all horses during each treatment. Electrical impedance tomography (EIT) data were recorded in four horses and used to generate functional EIT variables including regional ventilation delay index (RVD), a measure of speed of lung inflation, and end-expiratory lung impedance (EELI), an indicator of functional residual capacity (FRC). Results were assessed with linear and generalized linear mixed models. RESULTS: Compared with treatment IE1:3, horses ventilated with treatment IE1:1 had higher mean airway pressures and respiratory system compliance (p < 0.014), while peak, end-inspiratory and driving airway pressures were lower (p < 0.001). No differences in arterial oxygenation or dobutamine requirements were observed. PaCO2 was lower in treatment IE1:1 (p = 0.039). Treatment IE1:1 resulted in lower RVD (p < 0.002) and higher EELI (p = 0.023) than treatment IE1:3. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that IE1:1 improved respiratory system mechanics and alveolar ventilation compared with IE1:3, whereas oxygenation and dobutamine requirements were unchanged, although differences were small. In the four horses where EIT was evaluated, IE1:1 led to a faster inflation rate of the lung, possibly the result of increased FRC. The clinical relevance of these findings needs to be further investigated.


Assuntos
Dobutamina , Respiração com Pressão Positiva , Cavalos , Animais , Volume de Ventilação Pulmonar , Respiração com Pressão Positiva/veterinária , Gasometria/veterinária , Respiração , Impedância Elétrica
5.
J Am Chem Soc ; 143(10): 3901-3910, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33660996

RESUMO

Alkenes, ethers, and alcohols account for a significant percentage of bulk reagents available to the chemistry community. The petrochemical, pharmaceutical, and agrochemical industries each consume gigagrams of these materials as fuels and solvents each year. However, the utilization of such materials as building blocks for the construction of complex small molecules is limited by the necessity of prefunctionalization to achieve chemoselective reactivity. Herein, we report the implementation of efficient, sustainable, diaryl ketone hydrogen-atom transfer (HAT) catalysis to activate native C-H bonds for multicomponent dicarbofunctionalization of alkenes. The ability to forge new carbon-carbon bonds between reagents typically viewed as commodity solvents provides a new, more atom-economic outlook for organic synthesis. Through detailed experimental and computational investigation, the critical effect of hydrogen bonding on the reactivity of this transformation was uncovered.


Assuntos
Alcenos/química , Níquel/química , Alcenos/síntese química , Carbono/química , Catálise , Hidrogênio/química , Ligação de Hidrogênio , Teoria Quântica
6.
J Am Chem Soc ; 143(47): 19648-19654, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34793157

RESUMO

The installation of gem-difluoromethylene groups into organic structures remains a daunting synthetic challenge despite their attractive structural, physical, and biochemical properties. A very efficient retrosynthetic approach would be the functionalization of a single C-F bond from a trifluoromethyl group. Recent advances in this line of attack have enabled the C-F activation of trifluoromethylarenes, but limit the accessible motifs to only benzylic gem-difluorinated scaffolds. In contrast, the C-F activation of trifluoroacetates would enable their use as a bifunctional gem-difluoromethylene synthon. Herein, we report a photochemically mediated method for the defluorinative alkylation of a commodity feedstock: ethyl trifluoroacetate. A novel mechanistic approach was identified using our previously developed diaryl ketone HAT catalyst to enable the hydroalkylation of a diverse suite of alkenes. Furthermore, electrochemical studies revealed that more challenging radical precursors, namely trifluoroacetamides, could also be functionalized via synergistic Lewis acid/photochemical activation. Finally, this method enabled a concise synthetic approach to novel gem-difluoro analogs of FDA-approved pharmaceutical compounds.


Assuntos
Acetamidas/química , Ésteres/síntese química , Fluoracetatos/química , Alcenos/química , Alquilação , Catálise/efeitos da radiação , Cetonas/química , Cetonas/efeitos da radiação , Estrutura Molecular
7.
FASEB J ; 34(12): 15875-15887, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047392

RESUMO

It is becoming clear that several human pathologies are caused by altered metabolic adaptations. During liver development, there are physiological changes, from the predominant utilization of glucose (fetal life) to the use of lipids (postnatal life). Fasting is another physiological stress that elicits well-known metabolic adjustments. We have reported the metabolic properties of cardiotrophin-1 (CT-1), a member of the interleukin-6 family of cytokines. Here, we aimed at analyzing the role of CT-1 in response to these metabolic changes. We used different in vivo models. Furthermore, a differential study was carried out with wild-type and CT-1 null mice in fed (ad libitum) and food-restricted conditions. We demonstrated that Ct-1 is a metabolic gene induced in the liver via PPARα in response to lipids in mice (neonates- and food-restricted adults). We found that Ct-1 mRNA expression in white adipose tissue directly involved PPARα and PPARγ. Finally, the physiological role of CT-1 in fasting is confirmed by the impaired food restriction-induced adipose tissue lipid mobilization in CT-1 null mice. Our findings support a previously unrecognized physiological role of CT-1 in metabolic adaptations, through the regulation of lipid metabolism and contributes to fasting-induced free fatty acid mobilization.


Assuntos
Adaptação Fisiológica/fisiologia , Jejum/metabolismo , Metabolismo dos Lipídeos/fisiologia , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Células 3T3 , Tecido Adiposo Branco/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR alfa/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/metabolismo
8.
Int J Behav Med ; 28(3): 372-381, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32869166

RESUMO

BACKGROUND: Mechanisms underlying exercise-induced mood enhancement are not well understood, but it is plausible that adaptive changes in attention to emotional stimuli underlie this effect. Thus, this study examined the effects of acute aerobic exercise on eye-tracking metrics while participants viewed emotionally expressive faces. METHODS: Thirty-four adults (18 women) aged 21.1 ± 1.4 years completed two counterbalanced 30-min conditions: vigorous running or seated rest. Eye tracking occurred pre- and 20-min post-condition. Participants viewed positive (n = 15), negative (n = 15), and neutral (n = 15) emotional facial expressions from the NimStim repository. Fixation duration, longest fixation, number of fixations, and scan path length were analyzed using repeated measures ANOVAs. RESULTS: Exercise improved mood, but had no effect on the dependent measures (all 3-way interactions p > 0.66). However, a main effect of emotionally expressive content for fixation duration (p = 0.04, η = 0.10) and a marginally significant effect for longest fixation (p = 0.06, ηp2 = 0.09) were detected, such that fixation duration and longest fixation were greatest for faces expressing positive emotions. CONCLUSION: These preliminary findings indicated that acute exercise did not alter the processing of expressive faces as indexed by eye-tracking metrics of attention. However, eye tracking effectively detected processing patterns indicative of a pleasure bias while viewing emotional facial expressions.

9.
Can J Surg ; 63(6): E581-E593, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33278908

RESUMO

Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.


L'humanité est à l'aube d'une nouvelle ère d'exploration spatiale, mais le risque de maladies et blessures graves pourrait restreindre de manière catastrophique le potentiel des voyages dans l'espace. L'être humain est un superorganisme vivant en symbiose avec son microbiote, dont la diversité génétique éclipse celle de l'hôte. Cette symbiose est essentielle : tout déséquilibre est associé à une dégradation de l'état de santé dans les heures suivant l'occurrence d'une blessure ou d'une maladie grave. Bon nombre de caractéristiques propres au vol spatial ont des répercussions négatives sur le microbiote; l'espace lointain présente des dangers particuliers en raison de l'exposition accrue au rayonnement et de l'absence de gravité. L'exposition prolongée à l'apesanteur cause une myriade de changements physiologiques nuisant à la santé. Certains ressemblent à des processus de vieillissement et réduiront la capacité à tolérer une blessure ou une maladie grave et son traitement. L'hypertension intra-abdominale (HIA) causée par une maladie grave peut réduire la perfusion des viscères et du microbiote, ce qui peut avoir des conséquences catastrophiques. Des études sur modèle animal ont confirmé les effets profondément délétères de l'HIA sur les intestins par l'apparition d'une ischémie et une altération de la barrière intestinale; cette découverte permettrait d'établir un lien mécanistique entre l'HIA et la défaillance d'organes résultante. Par conséquent, une dysbiose pathologique, associée à un dysfonctionnement immunitaire en apesanteur et à une réduction de la réserve cardiorespiratoire accompagnée d'une exacerbation de la susceptibilité à l'HIA, pourrait signifier qu'un astronaute exposé à l'effet déconditionnant de l'apesanteur serait vulnérable aux problèmes de perfusion de l'intestin découlant de l'HIA. Ce problème pourrait à son tour mener à une ischémie intestinale grave et à une production massive de biomédiateurs chez un astronaute présentant déjà une capacité cardiorespiratoire et immunitaire réduite. Heureusement, des expériences dans des environnements simulant l'apesanteur semblent indiquer que les effets de l'HIA pourraient être contrés par des changements conformationnels de la paroi abdominale et un rétablissement de la mécanique thoracoabdominale. Par conséquent, un examen des interactions des changements physiologiques associés à un état d'apesanteur prolongé et à l'HIA est requis pour déterminer les questions à poser afin de planifier adéquatement les soins chirurgicaux en contexte d'exploration spatiale.


Assuntos
Disbiose/fisiopatologia , Hipertensão Intra-Abdominal/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Voo Espacial , Ausência de Peso/efeitos adversos , Abdome/fisiopatologia , Animais , Estado Terminal , Disbiose/etiologia , Disbiose/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Humanos , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intra-Abdominal/prevenção & controle , Modelos Animais , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle
10.
Adm Policy Ment Health ; 47(2): 188-196, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31197625

RESUMO

Tools to monitor implementation progress could facilitate scale-up of effective treatments. Most treatment for depression, a common and disabling condition, is provided in primary care settings. Collaborative Care Management (CoCM) is an evidence-based model for treating common mental health conditions, including depression, in this setting; yet, it is not widely implemented. The Stages of Implementation Completion (SIC) was adapted for CoCM and piloted in eight rural primary care clinics serving adults challenged by low-income status. The CoCM-SIC accurately assessed implementation effectiveness and detected site variations in performance, suggesting key implementation activities to aid future scale-ups of CoCM for diverse populations.


Assuntos
Depressão/terapia , Ciência da Implementação , Serviços de Saúde Mental/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Atenção Primária à Saúde/organização & administração , Competência Clínica , Comportamento Cooperativo , Acessibilidade aos Serviços de Saúde , Humanos , Serviços de Saúde Rural/organização & administração
11.
J Am Chem Soc ; 141(51): 20069-20078, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31833357

RESUMO

An intermolecular, photocatalytic dicarbofunctionalization (DCF) of olefins enabled by the merger of Giese-type addition with Ni/photoredox dual catalysis has been realized. Capitalizing on the rapid addition of 3° radicals to alkenes and their reluctance toward single electron metalation to Ni complexes, regioselective alkylation and arylation of olefins is possible. This dual catalytic method not only permits elaborate species to be assembled from commodity materials, but also allows quaternary and tertiary centers to be installed in a singular, chemoselective olefin difunctionalization. This multicomponent process occurs under exceptionally mild conditions, compatible with a diverse range of functional groups and synthetic handles such as pinacolboronate esters. This technology was directly applied to the synthesis of an intermediate to a preclinical candidate (TK-666) and its derivatives.


Assuntos
Alcenos/química , Níquel/química , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos
12.
Child Welfare ; 97(5): 179-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-33281198

RESUMO

Treatment Foster Care Oregon (TFCO) is an alternative to congregate care, for youth involved in the juvenile justice and/or child welfare systems. Though demonstrated as clinically-and cost-effective across multiple rigorous trials, the long-term cost benefit of TFCO has not been considered. This study follows n = 166 females from adolescence to young adulthood, who were involved in both systems and referred for out-of-home-care. Records of arrest, court, incarceration (juvenile, jail, and prison), monitoring (parole and probation) and child-welfare services were included in a long-term cost-benefit analysis. Outcomes highlight ongoing benefit of the TFCO intervention, nearly 10 years post-intervention.

13.
Diabetes Obes Metab ; 20(10): 2339-2350, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29790245

RESUMO

AIMS: Familial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPARγ. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated with this mutation using a humanized mouse model that recapitulates most of the clinical symptoms observed in patients who have been phenotyped under different experimental conditions. One of the key clinical manifestations observed, both in humans and mouse models, is the ectopic accumulation of fat in the liver. With this study we aim to dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterize the negative effect of this PPARγ mutation on the activity of PPARα in vivo when activated by fibrates. MATERIAL AND METHODS: P465L-PPAR mutant and wild-type mice were divided into 8 experimental groups, 4 different conditions per genotype. Briefly, mice were fed a chow diet or a high-fat diet (HFD 45% Kcal from fat) for a period of 28 days and treated with WY14643 or vehicle for five days before culling. At the end of the experiment, tissues and plasma were collected. We performed extensive gene expression, fatty acid composition and histological analysis in the livers. The serum collected was used to measure several metabolites and to perform basic lipoprotein profile. RESULTS: P465L mice showed increased levels of insulin and free fatty acids (FFA) as well as increased liver steatosis. They also exhibit decreased levels of very low density lipoproteins (VLDL) when fed an HFD. We also provide evidence of impaired expression of a number of well-established PPARα target genes in the P465L mutant livers. CONCLUSION: Our data demonstrate that P465L confers partial resistance to the hypolipidemic action of fibrates. These results show that the fatty liver phenotype observed in P465L mutant mice is not only the consequence of dysfunctional adipose tissue, but also involves defective liver metabolism. All in all, the deleterious effects of P465L-PPARγ mutation may be magnified by their collateral negative effect on PPARα function.


Assuntos
Resistência a Medicamentos/genética , Fígado Gorduroso/tratamento farmacológico , Ácidos Fíbricos/uso terapêutico , Hipolipemiantes/uso terapêutico , Mutação de Sentido Incorreto , PPAR gama/genética , Substituição de Aminoácidos , Animais , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/genética , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Leucina/genética , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto/fisiologia , Prolina/genética
14.
Biochem J ; 474(14): 2489-2508, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28341808

RESUMO

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions.


Assuntos
Coenzima A/metabolismo , Proteínas/metabolismo , Animais , Cisteína/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Rim/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Especificidade de Órgãos , Oxirredução , Estresse Oxidativo , Processamento de Proteína Pós-Traducional , Coelhos , Ratos Sprague-Dawley , Compostos de Sulfidrila/metabolismo
15.
Int J Technol Assess Health Care ; 34(4): 419-424, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30025548

RESUMO

OBJECTIVES: Large numbers of new medical devices and diagnostics are developed and health services need to identify which ones offer real advantages. The National Institute for Health and Care Excellence (NICE) has introduced a system for assessing technologies that are often notified by companies, based on claims made for their benefits to patients, the National Health Service, and the environment. METHODS: Detailed scrutiny of claims made for the benefits of products and the corresponding evidence, seeking associations between these and the selection of products for full evaluation to produce NICE guidance. RESULTS: Between 2009 and 2015 a NICE committee considered 169 technologies, of which it selected 74 (44 percent) for full evaluation, based on the claims of benefit and the evidence available. An average of 7.5 claims were made per technology; the total number did not influence selection but presence of studies supporting all the claims (p < .001) or any of the claims (p < .05) had a positive influence, as did claims for quicker patient recovery (p < .001). A greater number of studies to support the claims made selection more likely (p < .001), as did cohort studies (p < .05) and surveys (p < .05) but, unexpectedly, not randomized trials. The Medical Device Directive class had no influence. CONCLUSIONS: This study presents categories of claims that may be useful to those developing new products and to others engaged in health technology assessment. It illustrates the importance of relevant evidence and of having a clear vision of the place of new products in care pathways from an early stage.


Assuntos
Técnicas e Procedimentos Diagnósticos/normas , Equipamentos e Provisões/normas , Medicina Estatal/organização & administração , Avaliação da Tecnologia Biomédica/organização & administração , Redução de Custos , Análise Custo-Benefício , Técnicas e Procedimentos Diagnósticos/economia , Equipamentos e Provisões/economia , Humanos , Segurança do Paciente , Reprodutibilidade dos Testes , Medicina Estatal/normas , Avaliação da Tecnologia Biomédica/normas , Reino Unido
16.
Mol Med ; 22: 724-736, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27782293

RESUMO

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented the expansion of the perigonadal depot while at the same time exacerbating inflammation. PPARγ2KO pregnant mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential to promote healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.

17.
Perspect Biol Med ; 59(3): 364-381, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28479578

RESUMO

Can scientists self-regulate effectively? The controversial select agent regulations, the recent implementation of U.S. dual-use research of concern policies, the funding moratorium on gain of function experiments, and the 2014 incidents at the Centers for Disease Control and Prevention all seem to suggest that the answer is a resounding "no." Yet history tells us that it is feasible. In this comprehensive history of the first iteration of the National Institutes of Health (NIH) Recombinant DNA Guidelines, we examine the principles, thoughts, and behaviors that resulted in successful self-regulation of scientific research for the past four decades and how engagement of scientists made it possible. Starting with a willingness on the part of researchers all over the world to pause exciting experiments, and with a genuine concern for public health, the individuals involved demonstrated unprecedented (and thus far never replicated) openness to dialogue with others from different disciplines, the media, and the public.


Assuntos
Ética em Pesquisa , Pesquisa/normas , Centers for Disease Control and Prevention, U.S. , Guias como Assunto/normas , Humanos , Comunicação Interdisciplinar , National Institutes of Health (U.S.) , Estados Unidos
18.
Clin Infect Dis ; 61(10): 1514-20, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26240199

RESUMO

BACKGROUND: Tenosynovitis is an uncommon manifestation of disseminated infection with Coccidioides fungal species. Most experts treat this infection with combined surgical debridement and antifungal medication. The aim of our study was to examine the outcomes of patients with coccidioidal tenosynovitis of the hand and wrist. METHODS: We retrospectively searched for the records of patients with coccidioidal tenosynovitis of the hand and wrist at our institution. between 1987 and 2013. We also conducted a review of the literature from 1950 to 2014 to identify additional cases. RESULTS: We identified 9 cases of coccidioidal tenosynovitis of the hand and wrist at our institution, along with 5 other cases found in a review of the literature. The relapse rate was high overall (50%) and was higher after discontinuation of antifungal therapy (71%) in both immunocompromised and immunocompetent patients. Results of serologic testing were not predictive of relapse. CONCLUSIONS: A treatment strategy for coccidioidal tenosynovitis should focus on long-term administration of antifungal agents.


Assuntos
Coccidioides/isolamento & purificação , Coccidioidomicose/diagnóstico , Coccidioidomicose/patologia , Mãos/patologia , Tenossinovite/diagnóstico , Tenossinovite/patologia , Punho/patologia , Adulto , Idoso , Antifúngicos/uso terapêutico , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/cirurgia , Desbridamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenossinovite/tratamento farmacológico , Tenossinovite/cirurgia , Resultado do Tratamento , Adulto Jovem
20.
J Zoo Wildl Med ; 46(3): 629-32, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26352976

RESUMO

A 17-yr-old boa constrictor (Boa constrictor constrictor) presented initially with diffuse gingival swelling, loose teeth, and loss of body condition. Examination under anesthesia revealed two firm pink masses within the oral cavity. The largest mass was removed for biopsy. Histopathology and Melan-A-positive immunohistochemistry labeling confirmed a diagnosis of amelanotic melanoma. Secondary stomatitis was treated with antibiotics to improve quality of life, but the snake's condition deteriorated quickly over the next 2 mo. Euthanasia was elected and a gross postmortem examination was performed. Gross postmortem examination and histopathology results demonstrated that the neoplastic cells had spread in an unusual symmetrical pattern along all four dental arcades: the right and left sides of both the mandible and maxilla. Histopathology confirmed metastasis throughout the liver and spleen, despite the lack of gross lesions.


Assuntos
Boidae , Melanoma Amelanótico/veterinária , Neoplasias Bucais/veterinária , Animais , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia
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