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1.
Sociol Health Illn ; 46(2): 276-294, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37596959

RESUMO

Over the twentieth century, the concept of the natural experiment has become increasingly prominent across a variety of disciplines, albeit most consequentially in epidemiology and public health. Drawing on an analysis of the scientific and medical literature, we explore the social life of the natural experiment, tracing its changing use, meaning and uptake to better understand the work done by the concept. We demonstrate how the natural experiment became central to the identity of post-war epidemiology as the discipline professionalised, turned its attention to the prevention of chronic disease and took centre stage in the field of public health. We then turn to its growing significance amid the rise of evidence-based medicine, and the new meanings natural experiments came to take on in the context of concerns about policy and evidence. Finally, we turn to the newest iteration of the natural experiment in the COVID-19 era, which saw an explosion of studies drawing on the term, albeit in ways that reveal more about the underlying politics of health than the method itself. Throughout, we illustrate that the concept of the natural experiment has always been fundamentally social and political and tied to disciplinary claims-making about evidence and what should count as such.


Assuntos
Política , Saúde Pública , Humanos
2.
Sci Technol Human Values ; 49(1): 78-104, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38046188

RESUMO

Over the past decade, the phenomenon of "fake" peer reviews has caused growing consternation among scholarly publishers. Yet despite the significant behind-the-scenes impact that anxieties about fakery have had on peer review processes within scholarly journals, the phenomenon itself has been subject to little scholarly analysis. Rather than treating fake reviews as a straightforward descriptive category, in this article, we explore how the discourse on fake reviews emerged and why, and what it tells us about its seeming antithesis, "genuine" peer review. Our primary source of data are two influential adjudicators of scholarly publishing integrity that have been critical to the emergence of the concept of the fake review: Retraction Watch and the Committee on Publication Ethics. Via an analysis of their respective blog posts, Forum cases, presentations, and best practice guidance, we build a genealogy of the fake review discourse and highlight the variety of players involved in staking out the fake. We conclude that constant work is required to maintain clear lines of separation between genuine and fake reviews and highlight how the concept has served to reassert the boundaries between science and society in a context where they have increasingly been questioned.

3.
J Ultrasound Med ; 41(9): 2355-2364, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34921442

RESUMO

OBJECTIVES: Ultrasound measurements of muscle echo intensity are commonly used surrogates of muscle composition (eg, intramuscular adipose tissue). However, given that soundwaves are increasingly attenuated with tissue depth, the interpretation of echo intensity may be confounded by adipose and skeletal muscle thickness. Our objectives are to compare the associations between adipose or muscle tissue thickness and rectus femoris echo intensity in younger and older males and females. METHODS: Participants included in this analysis were derived from 3 previously published cohorts of younger (<45 years) and older (≥60 years) males and females. Ultrasound images of the rectus femoris were evaluated for muscle thickness, echo intensity, and subcutaneous adipose tissue thickness. RESULTS: Older adults (n: 49 males, 19 females) had a higher body mass index (P = .001) compared with younger adults (n: 37 males, 49 females). Muscle thickness was negatively associated with echo intensity in older males (r = -0.59) and females (r = -0.53), whereas no associations were observed in younger males (r = 0.00) or females (r = -0.11). Subcutaneous adipose tissue thickness displayed no associations with echo intensity in any group. CONCLUSIONS: Despite the known influence of subcutaneous adipose tissue thickness on beam attenuation, we observed no association with muscle echo intensity, indicating that adipose tissue correction may be required to better understand muscle echo intensity across differences in adiposity. The negative associations between muscle thickness and echo intensity in older, but not younger adults, suggests these associations may be related to the co-occurrence of skeletal muscle atrophy and intramuscular adipose tissue infiltration with advancing age.


Assuntos
Músculo Esquelético , Músculo Quadríceps , Tecido Adiposo/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Quadríceps/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Ultrassonografia/métodos
4.
FASEB J ; 34(7): 8975-8989, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32463134

RESUMO

Skeletal muscle satellite cell (SC) function and responsiveness is regulated, in part, through interactions within the niche, in which they reside. Evidence suggests that structural changes occur in the SC niche as a function of aging. In the present study, we investigated the impact of aging on SC niche properties. Muscle biopsies were obtained from the vastus lateralis of healthy young (YM; 21 ± 1 yr; n = 10) and older men (OM; 68 ± 1 yr; n = 16) at rest. A separate group of OM performed a single bout of resistance exercise and additional muscle biopsies were taken 24 and 48 hours post-exercise; this was performed before and following 12 wks of combined exercise training (OM-Ex; 73 ± 1; n = 24). Muscle SC niche measurements were assessed using high resolution immunofluorescent confocal microscopy. Type II SC niche laminin thickness was greater in OM (1.86 ± 0.06 µm) as compared to YM (1.55 ± 0.09 µm, P < .05). The percentage of type II-associated SC that were completely surrounded by laminin was greater in OM (13.6%±4.2%) as compared to YM (3.5%±1.5%; P < .05). In non-surrounded SC, the proportion of active MyoD+ /Pax7+ SC were higher compared to surrounded SC (P < .05) following a single bout of exercise. This "incarceration" of the SC niche by laminin appears with aging and may inhibit SC activation in response to exercise.


Assuntos
Envelhecimento , Colágeno/metabolismo , Exercício Físico , Fibrose/fisiopatologia , Músculo Quadríceps/fisiologia , Células Satélites de Músculo Esquelético/fisiologia , Adaptação Fisiológica , Adulto , Idoso , Colágeno/classificação , Colágeno/genética , Regulação da Expressão Gênica , Humanos , Masculino , Músculo Quadríceps/citologia , Células Satélites de Músculo Esquelético/citologia , Adulto Jovem
5.
Am J Physiol Cell Physiol ; 316(3): C444-C448, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649918

RESUMO

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1-4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults.


Assuntos
Exercício Físico/fisiologia , Expressão Gênica/fisiologia , Cinurenina/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Idoso , Humanos , Masculino , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo
6.
J Physiol ; 597(1): 105-119, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370532

RESUMO

KEY POINTS: Skeletal muscle stem cells, termed satellite cells, play a crucial role in repair and remodelling of muscle in response to exercise An age-related decline in satellite cell number and/or function has been hypothesized to be a key factor in the development of sarcopenia and/or the blunted muscle fibre adaptive response to prolonged exercise training in older persons We report that performing prolonged exercise training improves the acute type II muscle fibre satellite cell response following a single bout of resistance exercise in older men. The observed improvement in muscle satellite function is associated with an increase in muscle fibre capillarization following exercise training suggesting a possible functional link between capillarization and satellite cell function. ABSTRACT: Age-related type II muscle fibre atrophy is accompanied by a fibre type-specific decline in satellite cell number and function. Exercise training restores satellite cell quantity in older adults; however, whether it can restore the impaired satellite cell response to exercise in older adults remains unknown. Therefore we assessed the acute satellite cell response to a single exercise session before and after prolonged exercise training in older men. Fourteen older men (74 ± 8 years) participated in a 12-week exercise training programme (resistance exercise performed twice per week, high intensity interval training once per week). Before and after training, percutaneous biopsies from the vastus lateralis muscle were taken prior to and following 24 and 48 h of post-exercise recovery. Muscle fibre characteristics were evaluated by immunohistochemistry and mRNA expression by RT-PCR. Whereas no changes were observed in type II muscle fibres, type I muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise before the exercise training programme (P < 0.01). Following the exercise training programme, both type I and type II muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise (P < 0.05). The greater acute increase in type II muscle fibre satellite cell content at 24 h post-exercise recovery after training was correlated with an increase in type II muscle fibre capillarization (r = 0.671, P = 0.012). We show that the acute muscle satellite cell response following exercise can be improved by prolonged exercise training in older men.


Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Células Satélites de Músculo Esquelético/fisiologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Força Muscular
7.
J Nutr ; 148(6): 891-899, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29878269

RESUMO

Background: Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown. Objective: We assessed whether a multi-ingredient protein-based supplement taken over a prolonged period of time could alter the muscle satellite cell response after exercise in older men. Methods: Twenty-seven older men [mean ± SD age: 73 ± 1 y; mean ± SD body mass index (kg/m2): 28 ± 1] participated in a randomized double-blind experiment. Participants were randomly divided into an experimental (EXP) group (n = 13) who consumed a multi-ingredient protein-based supplement [30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg Ca, and 1500 mg n-3 (ω-3) polyunsaturated fatty acids] 2 times/d for 7 wk or a control (CON; 22 g maltodextrin) group (n = 14). After 7 wk of supplementation, all participants performed a single resistance exercise session, and muscle biopsy samples were taken from the vastus lateralis before and 24 and 48 h after exercise. Immunohistochemistry was used to assess the change in type I and II muscle fiber satellite cell content and activation status of the cells. In addition, mRNA expression of the myogenic regulatory factors was determined by using reverse transcriptase-polymerase chain reaction. Results: In response to the single bout of exercise, type I muscle fiber satellite cell content was significantly increased at 24 h (0.132 ± 0.015 and 0.131 ± 0.011 satellite cells/fiber in CON and EXP groups, respectively) and 48 h (0.126 ± 0.010 and 0.120 ± 0.012 satellite cells/fiber in CON and EXP groups, respectively) compared with pre-exercise (0.092 ± 0.007 and 0.118 ± 0.017 satellite cells/fiber in CON and EXP groups, respectively) muscle biopsy samples (P < 0.01), with no difference between the 2 groups. In both groups, we observed no significant changes in type II muscle fiber satellite cell content after exercise. Conclusion: Ingesting a multi-ingredient protein-based supplement for 7 wk did not alter the type I or II muscle fiber satellite cell response during postexercise recovery in older men. This trial was registered at www.clinicaltrials.gov as NCT02281331.


Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/fisiologia , Idoso , Cálcio/administração & dosagem , Cálcio/farmacologia , Creatina/administração & dosagem , Creatina/farmacologia , Método Duplo-Cego , Combinação de Medicamentos , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vitamina D/administração & dosagem , Vitamina D/farmacologia , Proteínas do Soro do Leite/administração & dosagem
8.
Bioorg Med Chem Lett ; 26(1): 60-7, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26614408

RESUMO

We have identified a class of azabenzimidazoles as potent and selective JAK1 inhibitors. Investigations into the SAR are presented along with the structural features required to achieve selectivity for JAK1 versus other JAK family members. An example from the series demonstrated highly selective inhibition of JAK1 versus JAK2 and JAK3, along with inhibition of pSTAT3 in vivo, enabling it to serve as a JAK1 selective tool compound to further probe the biology of JAK1 selective inhibitors.


Assuntos
Imidazóis/farmacologia , Janus Quinase 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Imidazóis/síntese química , Imidazóis/química , Janus Quinase 1/metabolismo , Camundongos , Camundongos Nus , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade
9.
Am J Public Health ; 105(2): e61-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25521883

RESUMO

The legislation of health warning labels on cigarette packaging is a major focus for tobacco control internationally and is a key component of the World Health Organization's Framework Convention on Tobacco Control. This population-level intervention is broadly supported as a vital measure for warning people about the health consequences of smoking. However, some components of this approach warrant close critical inspection. Through a qualitative content analysis of the imagery used on health warning labels from 4 countries, we consider how this imagery depicts people that smoke. By critically analyzing this aspect of the visual culture of tobacco control, we argue that this imagery has the potential for unintended consequences, and obscures the social and embodied contexts in which smoking is experienced.


Assuntos
Rotulagem de Produtos , Produtos do Tabaco/efeitos adversos , Austrália , Canadá , Humanos , Rotulagem de Produtos/métodos , Rotulagem de Produtos/normas , Prevenção do Hábito de Fumar , Reino Unido , Estados Unidos
10.
Cult Med Psychiatry ; 39(3): 380-98, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25374370

RESUMO

Ulysses contracts are a particular type of advance directive that has been advocated for use in mental health settings and addictions treatment. Taking their name from the legend of Ulysses, such contracts are distinctive insofar as they are designed to thwart certain anticipated future wishes rather than realize them. In this paper, I consider what Ulysses contracts reveal about contemporary conceptions of addiction and the self. Drawing on discussions of Ulysses contracts in the psychiatric and addictions literature, as well as historical and contemporary examples of such, I show that Ulysses contracts are premised on a split between the present 'rational' self and the future 'irrational' self, thereby reproducing a very particular notion of addiction--one that serves to naturalize certain ways of thinking about freedom, choice, coercion, and the self.


Assuntos
Diretivas Antecipadas/legislação & jurisprudência , Comportamento Aditivo/terapia , Transtornos Mentais/terapia , Psicoterapia Racional-Emotiva/métodos , Coerção , Liberdade , Humanos , Autonomia Pessoal
11.
Med Anthropol Q ; 29(2): 216-36, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25314663

RESUMO

In the era of evidence-based health care, conferences aimed at disseminating scientific knowledge perform an essential role in shaping policy and research agendas and transforming physician practice. Drawing on observations at two U.S. cancer prevention conferences aimed at knowledge translation, we examine the ways that evidence regarding the relationship between cancer and lifestyle is articulated and enacted. We show that characterizations of the evidence base at the conferences far outstripped what is presently known about the relationship between cancer and lifestyle. The messages presented to conference participants were also personalized and overtly moralistic, with attendees engaged not merely as practitioners but as members of the public at risk for cancer. We conclude that conferences seeking to bring together knowledge "makers" and knowledge "users" play a potentially important role in the production of scientific facts and are worthy of further study as distinct sites of knowledge production.


Assuntos
Medicina Baseada em Evidências , Estilo de Vida , Neoplasias , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Obesidade , Pesquisa Translacional Biomédica
12.
Can Oncol Nurs J ; 24(3): 166-8, 174-7, 2014.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-25189054

RESUMO

A growing body of research informed by theories and methods in the social sciences and humanities indicates that certain problematic messages are commonly embedded in popular and oncological representations of cancer. Becoming more aware of these underlying messages has the potential to improve the ways clinicians think about and manage cancer. (Note: A written response to this article appears in Truant, Kohli, & Stephens (2014), Response to "Rethinking Assumptions about Cancer Survivorship": A Nursing Disciplinary Perspective, Canadian Oncology Nursing Journal, Vol. 24, Issue 3, p. 169).


Assuntos
Neoplasias/fisiopatologia , Sobreviventes , Canadá , Humanos
13.
Plant Cell ; 22(8): 2594-617, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20798327

RESUMO

Restriction of phosphoenolpyruvate (PEP) supply to plastids causes lethality of female and male gametophytes in Arabidopsis thaliana defective in both a phosphoenolpyruvate/phosphate translocator (PPT) of the inner envelope membrane and the plastid-localized enolase (ENO1) involved in glycolytic PEP provision. Homozygous double mutants of cue1 (defective in PPT1) and eno1 could not be obtained, and homozygous cue1 heterozygous eno1 mutants [cue1/eno1(+/-)] exhibited retarded vegetative growth, disturbed flower development, and up to 80% seed abortion. The phenotypes of diminished oil in seeds, reduced flavonoids and aromatic amino acids in flowers, compromised lignin biosynthesis in stems, and aberrant exine formation in pollen indicate that cue1/eno1(+/-) disrupts multiple pathways. While diminished fatty acid biosynthesis from PEP via plastidial pyruvate kinase appears to affect seed abortion, a restriction in the shikimate pathway affects formation of sporopollonin in the tapetum and lignin in the stem. Vegetative parts of cue1/eno1(+/-) contained increased free amino acids and jasmonic acid but had normal wax biosynthesis. ENO1 overexpression in cue1 rescued the leaf and root phenotypes, restored photosynthetic capacity, and improved seed yield and oil contents. In chloroplasts, ENO1 might be the only enzyme missing for a complete plastidic glycolysis.


Assuntos
Arabidopsis/metabolismo , Células Germinativas Vegetais/crescimento & desenvolvimento , Fosfoenolpiruvato/metabolismo , Plastídeos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cruzamentos Genéticos , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Varredura , Mutação , Fenótipo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Plastídeos/genética , Pólen/ultraestrutura
14.
Br J Nutr ; 110(12): 2165-72, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23750536

RESUMO

Glutamate is linked to the glycolytic process, particularly when co-ingested with carbohydrate, but its effects on glucose metabolism are poorly characterised. The present study aimed to (1) specifically examine the effects of carbohydrate administration on circulating glutamate concentrations and (2) investigate the effect of increased glutamate availability, independent of carbohydrate ingestion, on glucose metabolism. A total of nine participants underwent four trials: (1) glutamate supplement+carbohydrate drink (GLU+CHO); (2) glutamate supplement+placebo drink (GLU); (3) placebo supplement+carbohydrate drink (CHO); (4) placebo supplement+placebo drink (CON). Following a fasting blood sample, participants ingested monosodium L-glutamate (MSG; 150 mg/kg body weight) or placebo capsules at each trial followed by a 75 g carbohydrate or a non-energy placebo drink 30 min later. Blood samples were taken at 0, 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min. Plasma glutamate concentrations were significantly elevated relative to baseline during the GLU (approximately 10-fold) and GLU+CHO trials (approximately 6-fold). The glucose response to a carbohydrate load was blunted when glutamate was increased in the circulation (peak serum glucose: 5.50 (SE 0.54) mmol/l during the GLU+CHO trial v. 7.69 (SE 0.53) mmol/l during the CHO trial, P< 0.05). On average, c-peptide results revealed that insulin secretion did not differ between the GLU+CHO and CHO trials; however, four participants demonstrated increased insulin secretion during the GLU+CHO trial and five participants demonstrated decreased insulin secretion under the same conditions. In conclusion, when administration is staggered, MSG and carbohydrate supplementation can be used to manipulate plasma glutamate; however, future studies should control for this dichotomous insulin response.


Assuntos
Glicemia/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Suplementos Nutricionais , Insulina/metabolismo , Glutamato de Sódio/farmacologia , Adulto , Peptídeo C/metabolismo , Carboidratos da Dieta/sangue , Humanos , Secreção de Insulina , Masculino , Valores de Referência , Glutamato de Sódio/sangue , Adulto Jovem
15.
Bioorg Med Chem Lett ; 23(10): 3105-10, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23562594

RESUMO

The discovery of the activating mutation V617F in the JH2 domain of Jak2 and the modulation of oncogenic Stat3 by Jak2 inhibitors have spurred a great interest in the inhibition of the Jak2/Stat pathway in oncology. In this Letter, we communicate the discovery of novel inhibitors of the Jak2/Stat5 axis, the N-(1H-pyrazol-3-yl)pyrimidin-2-amino derivatives. The rationale, synthesis and biological evaluation of these derivatives are reported. Two lead analogs from this series, 6 and 9, displayed prolonged residence time on Jak2, at enzymatic level. Although 6 and 9 exhibited moderate selectivity in a selected kinase panel, we chose to test these inhibitors in vivo as a consequence to their long residence time. However, extended inhibition of Jak2 due to the long residence time, in the form of inhibiting phosphorylation of downstream Stat5, was not recapitulated in an in vivo setting.


Assuntos
Descoberta de Drogas , Janus Quinase 2/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT5/antagonistas & inibidores , Animais , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Feminino , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Conformação Molecular , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Ratos , Ratos Wistar , Fator de Transcrição STAT5/metabolismo , Relação Estrutura-Atividade , Especificidade por Substrato , Fatores de Tempo
16.
BMC Plant Biol ; 12: 8, 2012 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-22248311

RESUMO

BACKGROUND: We have studied the impact of carbohydrate-starvation on the acclimation response to high light using Arabidopsis thaliana double mutants strongly impaired in the day- and night path of photoassimilate export from the chloroplast. A complete knock-out mutant of the triose phosphate/phosphate translocator (TPT; tpt-2 mutant) was crossed to mutants defective in (i) starch biosynthesis (adg1-1, pgm1 and pgi1-1; knock-outs of ADP-glucose pyrophosphorylase, plastidial phosphoglucomutase and phosphoglucose isomerase) or (ii) starch mobilization (sex1-3, knock-out of glucan water dikinase) as well as in (iii) maltose export from the chloroplast (mex1-2). RESULTS: All double mutants were viable and indistinguishable from the wild type when grown under low light conditions, but--except for sex1-3/tpt-2--developed a high chlorophyll fluorescence (HCF) phenotype and growth retardation when grown in high light. Immunoblots of thylakoid proteins, Blue-Native gel electrophoresis and chlorophyll fluorescence emission analyses at 77 Kelvin with the adg1-1/tpt-2 double mutant revealed that HCF was linked to a specific decrease in plastome-encoded core proteins of both photosystems (with the exception of the PSII component cytochrome b559), whereas nuclear-encoded antennae (LHCs) accumulated normally, but were predominantly not attached to their photosystems. Uncoupled antennae are the major cause for HCF of dark-adapted plants. Feeding of sucrose or glucose to high light-grown adg1-1/tpt-2 plants rescued the HCF- and growth phenotypes. Elevated sugar levels induce the expression of the glucose-6-phosphate/phosphate translocator2 (GPT2), which in principle could compensate for the deficiency in the TPT. A triple mutant with an additional defect in GPT2 (adg1-1/tpt-2/gpt2-1) exhibited an identical rescue of the HCF- and growth phenotype in response to sugar feeding as the adg1-1/tpt-2 double mutant, indicating that this rescue is independent from the sugar-triggered induction of GPT2. CONCLUSIONS: We propose that cytosolic carbohydrate availability modulates acclimation to high light in A. thaliana. It is conceivable that the strong relationship between the chloroplast and nucleus with respect to a co-ordinated expression of photosynthesis genes is modified in carbohydrate-starved plants. Hence carbohydrates may be considered as a novel component involved in chloroplast-to-nucleus retrograde signaling, an aspect that will be addressed in future studies.


Assuntos
Aclimatação , Arabidopsis/metabolismo , Metabolismo dos Carboidratos , Luz , Folhas de Planta/metabolismo , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Cruzamentos Genéticos , Citosol/metabolismo , Transporte de Elétrons , Fluorescência , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Genes de Plantas , Glucose-1-Fosfato Adenililtransferase/genética , Glucose-1-Fosfato Adenililtransferase/metabolismo , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Microscopia Eletrônica de Transmissão , Fenótipo , Fosfoglucomutase/genética , Fosfoglucomutase/metabolismo , Fotossíntese , Folhas de Planta/efeitos da radiação , Amido/biossíntese
17.
Cult Med Psychiatry ; 36(4): 584-600, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23054293

RESUMO

As numerous scholars have noted, cancer survivorship is often represented in popular discourse as providing an opportunity for a physical, emotional, and spiritual makeover. However, this idea that cancer enables the self to be remade on all levels is also increasingly evoked in the field of psychosocial oncology. Exploring cancer survivorship as a biopolitical phenomenon, I focus on two concepts that have become central to understandings of the disease: the "teachable moment" and "post-traumatic growth." Drawing primarily on representations of cancer survivorship in the clinical literature, I suggest that cancer is increasingly seen to present a unique opportunity to catalyze the patient's physical and psychological development. In this framework, the patient can no longer be relied upon to transform him or herself: this change must be externally driven, with clinicians taking advantage of the trauma that cancer entails to kick-start the patient into action. Broadening my analysis to the concepts of "trauma" and "development" writ large, I go on to suggest that survivorship discourse seems to partake of a larger and relatively recent meta-narrative about development-both individual and societal--and the positive opportunity that trauma is seen to present to stimulate reconstruction on a grand scale.


Assuntos
Neoplasias/psicologia , Estresse Psicológico/psicologia , Sobreviventes/psicologia , Humanos , Estresse Psicológico/etiologia
18.
Glob Public Health ; 17(8): 1467-1478, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34278948

RESUMO

The movement to decolonise global health is gathering pace. In its concern with the fundamental, distal causes of inequality and its call for social justice, the decolonisation movement forces us to question how global health works, for whom, where it is located, its funding practices, power asymmetries, cultures of collaboration and publication. This paper uses a new book by Harvard-based physician-anthropologist Eugene T. Richardson, Epidemic Illusions, as a point of departure for a broader analysis of the nature of global health knowledge, science, authorship, research and practice. Written in a 'carnivalesque' style, the book proceeds through a series of 'ironic (re)descriptions' to argue that global public health is an 'apparatus of coloniality'. In so doing, the book is generative of four ironic turns that we explore through the themes of guilt, humility, privilege and ambiguity. In locating these ironic turns within the broader landscape of global health, we reflect on whether the means of such a book achieve the ends of decolonisation.


Assuntos
Compreensão , Saúde Global , Humanos
19.
Appl Physiol Nutr Metab ; 47(5): 521-528, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35104155

RESUMO

Dual-energy X-ray absorptiometry (DXA) appendicular lean tissue is used to screen older adults for sarcopenia. However, emerging data indicates that ageing-related muscle atrophy largely occurs within specific muscles, which may be masked using appendicular lean tissue. Comparisons between appendicular lean tissue and site-specific measures of muscle in relation to strength and physical function are needed to advance our understanding of these features in the context of poor muscle function in aged adults. Our primary objective was to compare correlations between lean tissue and site-specific muscle characteristics in relation to strength and physical function in older males. Older males (≥65 years) were evaluated for muscle strength, physical function (6-minute walk and 30-second sit-to-stand), and muscle size (appendicular and site-specific) and composition (echo intensity) using DXA and ultrasound. Of the 32 older males (75.4 ± 7.9 years), 12 had low appendicular lean tissue. All DXA and ultrasound muscle characteristics were associated (r = 0.39 to 0.83, p < 0.05) with torque or power producing capabilities. Except for the knee flexors, no differences in correlation coefficients were observed between muscle thickness or regional lean tissue in relation to muscle strength. Neither DXA nor ultrasound muscle characteristics were associated with physical function. In older males, ultrasound-based muscle thickness and DXA lean tissue provided similar associations with strength. Novelty: Lean tissue and muscle thickness provide similar associations with strength. Muscle thickness can distinguish low and normal appendicular lean tissue in older adults.


Assuntos
Músculo Esquelético , Sarcopenia , Absorciometria de Fóton , Idoso , Envelhecimento , Composição Corporal , Força da Mão , Humanos , Masculino , Força Muscular/fisiologia , Músculo Esquelético/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem
20.
Eur J Clin Nutr ; 76(7): 958-963, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35046565

RESUMO

BACKGROUND: Ultrasound measurements of the anterior upper leg muscle thickness are often used to quantify muscle mass; however, the ideal normalization approach is unclear. Our primary objective was to examine how the anterior upper leg muscle thickness scales with indices of body size in younger and older adults. Our secondary objectives were to examine how normalization with body size alters the identification of low muscle thickness and associations with strength and physical function. METHODS: Younger (<45 years) males (n = 38) and females (n = 24) and older (≥60 years) males (n = 53) and females (n = 24) were evaluated for anthropometrics and anterior upper leg muscle thickness. Allometric models were used to examine how body size metrics scale with anterior upper leg muscle thickness. A subset of older males was evaluated for strength and function. RESULTS: Weight and BMI scaled with anterior upper leg muscle thickness with coefficients less than 1 (0.58 to 0.82, r2 = 0.15 to 0.31, p < 0.05) for both younger and older males and females. Compared to absolute anterior upper leg thickness, normalized indices identified a greater proportion of older adults with low muscle thickness (p < 0.05). Absolute muscle thickness provided stronger associations with strength compared to weight normalized indices. CONCLUSIONS: Scaling exponents less than 1 for weight and BMI for the anterior upper leg muscle thickness indicate that allometric normalization is the ideal approach to develop body size independent metrics. However, allometric normalization of muscle thickness increases the proportion of older adults classified as low muscle mass but decreased the associations with strength.


Assuntos
Perna (Membro) , Músculo Esquelético , Idoso , Antropometria , Tamanho Corporal , Feminino , Humanos , Masculino , Força Muscular/fisiologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Ultrassonografia
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