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2.
PLoS One ; 19(5): e0301184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696442

RESUMO

OBJECTIVES: Body dissatisfaction is often linked to the internalization of Western beauty standards. Existing measures of body dissatisfaction, developed in Western societies, may fail to capture complex variations across ethnicities and cultures. The Negative Physical Self Scale (NPSS) assesses cognitive, affective, perceptual, and behavioural facets of body dissatisfaction. While unique in its consideration of Chinese ideals of body image, the NPSS has recently been translated and validated in a North American sample. The English-translated version of the NPSS has the potential to be an appropriate body dissatisfaction assessment tool for Asian women living in North America. The current study aims to validate the NPSS in an Asian female population living in Canada. METHODS: A sample of 899 undergraduate women residing in Canada with self-identified Asian ethnicity completed an online survey consisting of the NPSS and other measures of body dissatisfaction. RESULTS: An initial confirmatory factor analysis indicated that the four-factor structure of the NPSS, previously suggested in a primarily non-Asian North American sample, was a poor fit for the data. A second-order multidimensional model, based on a model proposed during the original development of the NPSS in a Chinese sample, indicated good fit once items were removed due to loadings < .60. High internal consistency between subscales and strong convergent validity with other measures were demonstrated. Notably, the NPSS Body Concern subscale demonstrated high convergence with other popular measures of body dissatisfaction and has the potential for use as a brief measure of body dissatisfaction among North American Asian females in clinical and research settings. CONCLUSIONS: The NPSS provides a valid assessment of body dissatisfaction among a sample of Asian women living in Canada, a specific subpopulation that has not been previously investigated. The findings highlight the importance of developing culturally sensitive measures of body dissatisfaction for differing ethnic and cultural groups.


Assuntos
Povo Asiático , Imagem Corporal , Humanos , Feminino , Canadá , Adulto , Povo Asiático/psicologia , Adulto Jovem , Imagem Corporal/psicologia , Inquéritos e Questionários , Insatisfação Corporal/psicologia , Adolescente , Psicometria/métodos , Autoimagem
3.
J Appl Microbiol ; 135(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38637309

RESUMO

AIMS: To monitor severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination in vehicles operating in England during the pandemic, to better understand transmission risk of SARS-CoV-2 on public transport. METHODS AND RESULTS: We collected 1314 surface samples between December 2020 and April 2022 on trains and buses managed by five different transport operators. The presence of SARS-CoV-2 RNA was investigated through reverse transcription polymerase chain reaction (RT-PCR). SARS-CoV-2 RNA was found on 197 (15%) of the 1314 surfaces sampled, including seat head rests, handholds, and air extract grilles, but the levels of RNA recovered on those samples (median value of 23.4, interquartile range: 14.3-35.4, N gene copies per extraction) made the presence of infectious virus at the time of sampling extremely unlikely. However, detection rates varied over time with peaks broadly coinciding with times of high community transmission, when it was more likely that people infected with SARS-CoV-2 were travelling on public transport. CONCLUSION: During the pandemic, and as in other public spaces, low levels of SARS-CoV-2 RNA were found on surfaces associated with public transport.


Assuntos
COVID-19 , RNA Viral , SARS-CoV-2 , COVID-19/transmissão , COVID-19/virologia , COVID-19/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Inglaterra/epidemiologia , RNA Viral/genética , RNA Viral/análise , RNA Viral/isolamento & purificação , Humanos , Estudos Longitudinais , Veículos Automotores , Meios de Transporte
4.
Nat Cell Biol ; 26(3): 421-437, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38409327

RESUMO

Type 1 diabetes (T1D) is characterized by the destruction of pancreatic ß-cells. Several observations have renewed the interest in ß-cell RNA sensors and editors. Here, we report that N6-methyladenosine (m6A) is an adaptive ß-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m6A writer methyltransferase 3 (METTL3) levels increase drastically in ß-cells at T1D onset but rapidly decline with disease progression. m6A sequencing revealed the m6A hypermethylation of several key innate immune mediators, including OAS1, OAS2, OAS3 and ADAR1 in human islets and EndoC-ßH1 cells at T1D onset. METTL3 silencing enhanced 2'-5'-oligoadenylate synthetase levels by increasing its mRNA stability. Consistently, in vivo gene therapy to prolong Mettl3 overexpression specifically in ß-cells delayed diabetes progression in the non-obese diabetic mouse model of T1D. Mechanistically, the accumulation of reactive oxygen species blocked upregulation of METTL3 in response to cytokines, while physiological levels of nitric oxide enhanced METTL3 levels and activity. Furthermore, we report that the cysteines in position C276 and C326 in the zinc finger domains of the METTL3 protein are sensitive to S-nitrosylation and are important to the METTL3-mediated regulation of oligoadenylate synthase mRNA stability in human ß-cells. Collectively, we report that m6A regulates the innate immune response at the ß-cell level during the onset of T1D in humans.


Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Animais , Humanos , Camundongos , Adenosina Desaminase/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Imunidade Inata , Células Secretoras de Insulina/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Oxirredução
5.
J Sex Marital Ther ; 50(2): 137-151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37807833

RESUMO

Virtual Reality (VR)-based treatments for anxiety disorders are efficacious but there is a lack of research examining anxious responses to VR erotica, which could innovate treatments for sexual difficulties. We examined erotica features that elicited anxiety and sexual presence in women. Thirty-eight women viewed erotic videos from different modalities (2D, VR) and points of view (1st, 3rd person) and completed anxiety and sexual presence measures before and after each video. Women experienced greater anxiety for VR than 2D films and reported the most anxiety for VR 1st person films. Sexual presence was affected by modality and point of view.


Assuntos
Literatura Erótica , Realidade Virtual , Humanos , Feminino , Ansiedade , Comportamento Sexual/fisiologia , Transtornos de Ansiedade
6.
J Safety Res ; 87: 313-322, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38081704

RESUMO

INTRODUCTION: Speeding is a global road safety concern contributing to an excessive number of fatal crashes and serious debilitating injuries. Research identifying amendable factors associated with speeding to inform interventions is critical. METHOD: This study examined the association of habit, perceived legitimacy of enforcement, and deterrence elements with three levels of speeding behavior; low- (<10 km/hr over the posted speed limit), mid- (10-20 km/hr), and high-range (>20 km/hr) speeding. An online survey of 870 participants aged over 17 years (M = 37 years) was administered. RESULTS: Approximately 80% of participants reported low-range speeding, 40% mid-range speeding, and 20% high-range speeding. Differences were found between speeding on urban and open roads with the proportion of participants greater for mid- and high-range speeding on open roads. Multiple linear regressions were run finding habit and deterrence variables to be significant predictors of all three levels of speeding. Perceived legitimacy of enforcement was a significant predictor of high-range speeding only. PRACTICAL APPLICATIONS: These findings suggest countermeasures that encourage good speed-related habits would be promising. It is also concluded that additional deterrence measures that reduce punishment avoidance experiences (e.g., better detection of speeding behaviors) are needed to further curb speeding behaviors. Nevertheless, the current punishment for all levels of speeding is perceived to be an effective deterrent. These recommendations inform policy, training and education, and campaigns that target engagement in speeding.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Humanos , Idoso , Acidentes de Trânsito/prevenção & controle , Inquéritos e Questionários , Hábitos
7.
iScience ; 26(9): 107530, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664628

RESUMO

Ionizing radiation (IR) is a risk factor for acute myeloid leukemia (rAML). Murine rAMLs feature both hemizygous chromosome 2 deletions (Del2) and point mutations (R235) within the hematopoietic regulatory gene Spi1. We generated a heterozygous CBA Spi1 R235 mouse (CBASpm/+) which develops de novo AML with 100% incidence by ∼12 months old and shows a dose-dependent reduction in latency following X-irradiation. These effects are reduced on an AML-resistant C57Bl6 genetic background. CBASpm/Gfp reporter mice show increased Gfp expression, indicating compensation for Spm-induced Spi1 haploinsufficiency. Del2 is always detected in both de novo and rAMLs, indicating that biallelic Spi1 mutation is required for AML. CBASpm/+ mice show that a single Spm modification is sufficient for initiating AML development with complete penetrance, via the "two-hit" mechanism and this is accelerated by IR exposure. Similar SPI1/PU.1 polymorphisms in humans could potentially lead to enhanced susceptibility to IR following medical or environmental exposure.

8.
Nutr Res Rev ; : 1-24, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37746736

RESUMO

Certain nutritional practices may reduce menstrual-related symptoms, but there is no current consensus on what foods/supplements are sufficiently evidenced to warrant promotion to reduce menstrual symptoms of naturally menstruating individuals. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two online databases were searched for published experimental studies that investigated the effects of foods/supplements on menstrual-related symptoms in eumenorrhoeic women. Extracted data and study characteristics were tabulated and grouped on the basis of food/supplement intervention and dosage compared with UK dietary reference values (DRV) and safe upper limits. In total, twenty-eight studies and twenty-one different foods/supplement interventions were included in the review. None of the studies reported a negative effect on symptoms, twenty-three reported a positive effect and five had no effect. Eighteen different ways of measuring menstrual-related symptoms were described across the studies. The results indicate a lack of consistency in studies to confidently provide information to eumenorrheic, naturally menstruating women regarding the use of foods/supplements to reduce menstrual symptoms. Determination of menstrual-related symptoms varied along with dose and duration of food or supplements provided. These data provide some evidence for the use of vitamin D, calcium, zinc and curcumin to reduce menstrual-related symptoms of non-hormonal contraceptive users, on an individual basis; however, further investigation is required prior to implementation with a focus on robust protocols to determine and measure changes in menstrual symptoms, with interventions adhering to DRV and safe upper limits.

9.
bioRxiv ; 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37577492

RESUMO

N 6 -methyladenosine (m 6 A) is the most abundant chemical modification in mRNA, and plays important roles in human and mouse embryonic stem cell pluripotency, maintenance, and differentiation. We have recently reported, for the first time, the role of m 6 A in the postnatal control of ß-cell function in physiological states and in Type 1 and 2 Diabetes. However, the precise mechanisms by which m 6 A acts to regulate the development of human and mouse ß-cells are unexplored. Here, we show that the m 6 A landscape is dynamic during human pancreas development, and that METTL14, one of the m 6 A writer complex proteins, is essential for the early differentiation of both human and mouse ß-cells.

10.
Accid Anal Prev ; 191: 107190, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37441986

RESUMO

Professional driver education and training has traditionally been used to improve the driving skills of young people with the expectation that they will drive more safely and therefore be less likely to crash. Despite this, much research has failed to find such an effect. The Goals for Driver Education (GDE) is a theoretical framework developed to improve the effectiveness of driver education. The GDE seeks to draw attention to a broader array of factors that may influence the driving of young people and hence increase the scope of what is included in driver education and training. Within the GDE, factors affecting driving and driver education are grouped into combinations of four hierarchical levels that represent influences on driving at increasing levels of abstraction (GDE level 1: Vehicle manoeuvring; GDE level 2: Mastery of traffic situations; GDE level 3: Goals and contexts of driving; GDE level 4: Goals for life and skills for living) and three types of individual competencies (Knowledge and skills; Risk-increasing factors; Self-evaluation skills). However, to date there have been few, if any, attempts to operationalise the GDE in a quantitative way. In response, the Perceptions of Driver Education Scale (PDES) was developed to gain an understanding of what two important stakeholder groups in the driver education and training ecosystem perceived to be important to be taught to novice drivers. Understanding these perceptions may lead to greater acceptance of the driver education and training that is designed and make it more effective. Following rigorous scale development procedures, thirty-five items were developed a priori using expert opinion and deployed, via an online survey, to a sample of parents of novice drivers (N = 518) and a separate sample of novice drivers (N = 247), both from Queensland, Australia. Exploratory Factor Analysis was performed on the parent responses and Confirmatory Factor Analysis was performed using the novice driver responses. A 29-item 9 factor solution was judged to be the best fit with the overall scale and each of the factors displaying strong levels of internal consistency. The 9 factors cover most hierarchical level and competency combinations, although removal of items meant that there is no representation concerning perceptions of Self-evaluation skills related to Level 3: Goals and contexts of driving within the PDES. Overall, the PDES is a valid and reliable instrument for investigating the aspects of driver education and training that are perceived as important by novice drivers and parents. The scale may also be applicable for use with other stakeholder groups and could also be used to evaluate pre-existing driver education and training programs.


Assuntos
Condução de Veículo , Humanos , Adolescente , Condução de Veículo/educação , Acidentes de Trânsito/prevenção & controle , Ecossistema , Objetivos , Licenciamento , Pais
11.
Int J Sports Physiol Perform ; 18(9): 937-943, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37353219

RESUMO

PURPOSE: The potential impact of hormonal contraceptives (HCs) on player health and performance in women's rugby union (rugby) is not well understood, despite rugby's growing popularity worldwide. This study investigated the prevalence of HC use and reported associations with training and performance in a global sample of women rugby players. METHOD: A globally distributed online survey, seeking to explore experiences in women's rugby, was completed by 1596 current or former adult women 7s or 15s rugby players (mean age 27 [6] y; 7 [5] y playing experience) from 62 countries. The survey included a section of questions about reported HC use, including the type, reason for use, symptoms, and experiences relating to rugby training and performance. RESULTS: A total of 606 (38%) participants from 33 of the 62 (53%) countries reported using HCs, with the combined oral contraceptive pill reported as the most frequently used (44%). Almost half of participants using HCs (43%) tracked HC-related symptoms. Over 10% reported altered rugby performance due to HC-related symptoms, 22% required medication to manage symptoms, and 11% used HCs to control or stop their menstrual periods for rugby training and performance. CONCLUSIONS: The current study highlights the prevalence of HC use in women's rugby, identifying practices that may negatively affect performance, health, and well-being. Thus, there is an urgent need to better understand the motivations for such practices and knowledge of potential side effects among women rugby players across all levels and countries.


Assuntos
Futebol Americano , Rugby , Adulto , Humanos , Feminino , Menstruação , Inquéritos e Questionários , Anticoncepcionais Orais Combinados/efeitos adversos
12.
Mamm Biol ; : 1-21, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37363038

RESUMO

The common vampire bat (Desmodus rotundus) maintains a diverse, sanguivorous diet, utilizing a broad range of prey taxa. As anthropogenic change alters the distribution of this species, shifts in predator-prey interactions are expected. Understanding prey richness and patterns of prey selection is, thus, increasingly informative from ecological, epidemiological, and economic perspectives. We reviewed D. rotundus diet and assessed the geographical, taxonomical, and behavioral features to find 63 vertebrate species within 21 orders and 45 families constitute prey, including suitable host species in regions of invasion outside D. rotundus' range. Rodentia contained the largest number of species utilized by D. rotundus, though cattle were the most commonly reported prey source, likely linked to the high availability of livestock and visibility of bite wounds compared to wildlife. Additionally, there was tendency to predate upon species with diurnal activity and social behavior, potentially facilitating convenient and nocturnal predation. Our review highlights the dietary heterogeneity of D. rotundus across its distribution. We define D. rotundus as a generalist predator, or parasite, depending on the ecological definition of its symbiont roles in an ecosystem (i.e., lethal vs. non-lethal blood consumption). In view of the eminent role of D. rotundus in rabies virus transmission and its range expansion, an understanding of its ecology would benefit public health, wildlife management, and agriculture. Supplementary Information: The online version contains supplementary material available at 10.1007/s42991-023-00358-3.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37107757

RESUMO

Rugby Union (rugby) is a full-contact team sport characterised by frequent collision events. Over one third (2.7 million) of global rugby participants are women and girls. Yet, most rugby research, laws, and regulations are derived from the men's game with limited transferability to the women's game. This includes research focused on injury and concussion management. Greater insights are urgently required to enable appropriate adaptations and support for all rugby participants. Therefore, this paper presents the protocol for a project that sought to gather insights into the understanding, experiences, and attitudes of players and coaches in women's rugby regarding key issues of concussion, injury, and training for injury prevention, as well as the implications of the menstrual cycle for training and performance. From August 2020 to November 2020, online, open, cross-sectional surveys for players and coaches were distributed globally through rugby governing bodies and women's rugby social media platforms using snowball sampling. Survey responses were recorded anonymously via a GDPR-compliant online survey platform, JISC (jisc.ac.uk, Bristol, England). Participant eligibility included being ≥18 years and either actively playing or coaching women's rugby 15s and/or sevens, or having done so in the past decade, at any level, in any country. To enhance the number and accuracy of responses, the survey was professionally translated into eight additional languages. A total of 1596 participants from 62 countries (27 ± 6 years; 7.5 ± 5.1 years of playing experience) and 296 participants from 37 countries (mean age = 36.64, SD = 9.09, mean experience = 6.53 years, SD = 3.31) completed the players' and coaches' surveys, respectively. Understanding women's participation in and experiences of rugby is important to enable lifelong engagement and enjoyment of the sport and health during and following participation.


Assuntos
Concussão Encefálica , Futebol Americano , Masculino , Humanos , Feminino , Adulto , Estudos Transversais , Rugby , Futebol Americano/lesões , Internet
14.
Appl Environ Microbiol ; 89(3): e0174422, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36856438

RESUMO

The virucidal activity of the Zoono Z71 Microbe Shield surface sanitizer and protectant, a quaternary ammonium compound (QAC)-based antimicrobial coating that was used by the United Kingdom rail industry during the COVID-19 pandemic, was evaluated, using the bacteriophage ɸ6 as a surrogate for SARS-CoV-2. Immediately after application and in the absence of interfering substances, the product effectively reduced (>3 log10) the viability of ɸ6 on some materials that are typically used in rail carriages (stainless steel, high-pressure laminate, plastic). If, after the application of the product, these surfaces remained undisturbed, the antimicrobial coating retained its efficacy for at least 28 days. However, efficacy depended on the material being coated. The product provided inconsistent results when applied to glass surfaces and was ineffective (i.e., achieved <3 log10 reduction) when applied to a train arm rest that was made of Terluran 22. Regardless of the material that was coated or the time since application, the presence of organic debris (fetal bovine serum) significantly reduced the viricidal activity of the coating. Wiping the surface with a wetted cloth after the deposition of organic debris was not sufficient to restore efficacy. We conclude that the product is likely to be of limited effectiveness in a busy, multiuser environment, such as public transport. IMPORTANCE This study evaluated the performance of a commercially available antimicrobial coating that was used by the transport industry in the United Kingdom during the COVID-19 pandemic. While the product was effective against ɸ6, the efficacy of the coating depended upon the material to which it was applied. Similarly, and regardless of the surface material, the presence of organic debris severely impaired viricidal activity, and efficacy could not be recovered through wiping (cleaning) the surface. This highlights the importance of including relevant materials and conditions when evaluating antimicrobial coatings in the laboratory. Further efforts are required to identify suitable infection prevention and control practices for the transport industry.


Assuntos
Anti-Infecciosos , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Compostos de Amônio Quaternário/farmacologia , Pandemias/prevenção & controle , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico
15.
Res Sq ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36778367

RESUMO

Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of MS is well established, studies characterizing EBV-associated mechanisms of B cell inflammation and disease pathogenesis in EBV (+) B cells from MS patients are limited. Accordingly, we analyzed spontaneous lymphoblastoid cell lines (SLCLs) from multiple sclerosis patients and healthy controls to study host-virus interactions in B cells, in the context of an individual's endogenous EBV. We identify differences in EBV gene expression and regulation of both viral and cellular genes in SLCLs. Our data suggest that EBV latency is dysregulated in MS SLCLs with increased lytic gene expression observed in MS patient B cells, especially those generated from samples obtained during "active" disease. Moreover, we show increased inflammatory gene expression and cytokine production in MS patient SLCLs and demonstrate that tenofovir alafenamide, an antiviral that targets EBV replication, decreases EBV viral loads, EBV lytic gene expression, and EBV-mediated inflammation in both SLCLs and in a mixed lymphocyte assay. Collectively, these data suggest that dysregulation of EBV latency in MS drives a pro-inflammatory, pathogenic phenotype in memory B cells and that this response can be attenuated by suppressing EBV lytic activation. This study provides further support for the development of antiviral agents that target EBV-infection for use in MS.

16.
bioRxiv ; 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36824909

RESUMO

Type 1 Diabetes (T1D) is characterized by autoimmune-mediated destruction of insulin-producing ß-cells. Several observations have renewed interest in the innate immune system as an initiator of the disease process against ß-cells. Here, we show that N 6 -Methyladenosine (m 6 A) is an adaptive ß-cell safeguard mechanism that accelerates mRNA decay of the 2'-5'-oligoadenylate synthetase (OAS) genes to control the antiviral innate immune response at T1D onset. m 6 A writer methyltransferase 3 (METTL3) levels increase drastically in human and mouse ß-cells at T1D onset but rapidly decline with disease progression. Treatment of human islets and EndoC-ßH1 cells with pro-inflammatory cytokines interleukin-1 ß and interferon α mimicked the METTL3 upregulation seen at T1D onset. Furthermore, m 6 A-sequencing revealed the m 6 A hypermethylation of several key innate immune mediators including OAS1, OAS2, and OAS3 in human islets and EndoC-ßH1 cells challenged with cytokines. METTL3 silencing in human pseudoislets or EndoC-ßH1 cells enhanced OAS levels by increasing its mRNA stability upon cytokine challenge. Consistently, in vivo gene therapy, to prolong Mettl3 overexpression specifically in ß-cells, delayed diabetes progression in the non-obese diabetic (NOD) mouse model of T1D by limiting the upregulation of Oas pointing to potential therapeutic relevance. Mechanistically, the accumulation of reactive oxygen species blocked METTL3 upregulation in response to cytokines, while physiological levels of nitric oxide promoted its expression in human islets. Furthermore, for the first time to our knowledge, we show that the cysteines in position C276 and C326 in the zinc finger domain of the METTL3 protein are sensitive to S-nitrosylation (SNO) and are significant for the METTL3 mediated regulation of OAS mRNA stability in human ß-cells in response to cytokines. Collectively, we report that m 6 A regulates human and mouse ß-cells to control the innate immune response during the onset of T1D and propose targeting METTL3 to prevent ß-cell death in T1D.

17.
Cancer Discov ; 13(2): 298-311, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472553

RESUMO

Mutations in the KRAS oncogene are found in more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), with Gly-to-Asp mutations (KRASG12D) being the most common. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in implantable and autochthonous PDAC models with an intact immune system. In vitro studies validated the specificity and potency of MRTX1133. In vivo, MRTX1133 prompted deep tumor regressions in all models tested, including complete or near-complete remissions after 14 days. Concomitant with tumor cell apoptosis and proliferative arrest, drug treatment led to marked shifts in the tumor microenvironment (TME), including changes in fibroblasts, matrix, and macrophages. T cells were necessary for MRTX1133's full antitumor effect, and T-cell depletion accelerated tumor regrowth after therapy. These results validate the specificity, potency, and efficacy of MRTX1133 in immunocompetent KRASG12D-mutant PDAC models, providing a rationale for clinical testing and a platform for further investigation of combination therapies. SIGNIFICANCE: Pharmacologic inhibition of KRASG12D in pancreatic cancer models with an intact immune system stimulates specific, potent, and durable tumor regressions. In the absence of overt toxicity, these results suggest that this and similar inhibitors should be tested as potential, high-impact novel therapies for patients with PDAC. See related commentary by Redding and Grabocka, p. 260. This article is highlighted in the In This Issue feature, p. 247.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Mutação , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas p21(ras)/genética , Microambiente Tumoral , Neoplasias Pancreáticas
18.
Int J Sex Health ; 35(1): 139-151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38596767

RESUMO

Objectives: We examined changes in frequency of sexual behaviors, dyadic sexual desire, relationship satisfaction, and COVID-19 stress in Canadians across the pandemic, considering partner status. Methods: Participants completed online questionnaires. Results: Participants with live-in partners and single participants decreased in dyadic sexual behaviors. In August-September 2020, participants with live-in partners engaged in more dyadic sexual behaviors than single participants. In November 2021, all partnered participants engaged in more dyadic sexual behaviors than single participants. Decreases in COVID-19 stress were observed. Conclusions: Findings suggest that despite decreases in COVID-19 stress, there may be long-lasting pandemic impacts on sexual behaviors.

19.
eNeuro ; 9(5)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35995558

RESUMO

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA; 2 h/d) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here, we assess the effects of long-access (LgA; 6 h/d) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, employing a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive (∼40%) reductions in surface area, volume, and postsynaptic colocalization 45 d but not 24 h after the last self-administration session. In contrast, no effect of self-administration and abstinence was observed in astrocytes from female rats. Moreover, no effect of LgA self-administration and abstinence was observed on NAc GLT-1 expression in female rats, an effect that has been well described in males. These results indicate striking and sexually dimorphic effects of abstinence subsequent to LgA self-administration on astrocytes. Taken together, these results indicate a pivotal role of prolonged abstinence in the effects of cocaine self-administration on NAc astrocytes, and extend a growing body of evidence regarding sex differences in the cellular consequences of drug self-administration in the brain.


Assuntos
Cocaína , Metanfetamina , Animais , Astrócitos , Cocaína/farmacologia , Feminino , Heroína/farmacologia , Masculino , Metanfetamina/farmacologia , Núcleo Accumbens/metabolismo , Ratos , Autoadministração
20.
J Safety Res ; 82: 342-351, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36031262

RESUMO

INTRODUCTION: Engagement in prosocial and altruistic on-road behaviors is a new area of research with potential safety benefits for road users. This paper systematically reviewed studies on road users' engagement in prosocial and altruistic behaviors to provide guidance regarding the next steps in this area of research, particularly to inform targeted interventions. The objective was to identify the types of on-road prosocial and altruistic behaviors that have been studied, and the factors associated with these behaviors. Road users were defined as drivers, passengers, or vulnerable road users (e.g., pedestrian, motorcyclists, and bicyclists). METHOD: The database search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRIMSA) guidelines and was conducted in June 2021. A total of 23,090 articles were identified in four databases including APA PsycINFO, Embase, Web of Science, and the Transportation Research Information Database. Eleven articles (13 studies) published between 2004 and 2021 met the inclusion criteria and were included in the review. RESULTS: Six studies focused on intervening behaviors, specifically relating to passengers' willingness or intentions to speak up to a driver engaging in unsafe driving behaviors, four studies focused on drivers' yielding behaviors at crosswalks, and one study each focused on altruistic driving behaviors, prosocial driving behavior at long-wait stops, and prosocial behavior towards cyclists. Studies typically examined characteristics of the prosocial road user, including self-esteem, efficacy, and subjective norms, as well as contextual factors, such as other road users' behaviors and on-road messaging. CONCLUSIONS: This review highlights specific factors that may predict road users' engagement in prosocial and altruistic on-road behaviors. PRACTICAL APPLICATIONS: The outcomes from this review may be used to guide the development of future road safety public education messages designed to encourage greater participation in prosocial and altruistic on-road behaviors that act to benefit all road users.


Assuntos
Condução de Veículo , Pedestres , Acidentes de Trânsito , Altruísmo , Bases de Dados Factuais , Humanos
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