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1.
Int J Offender Ther Comp Criminol ; : 306624X241252037, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726616

RESUMO

The mechanism(s) through which child contact can lead to more positive mental health and romantic relationship outcomes among incarcerated fathers are not sufficiently studied. The present study tests whether the associations between frequency of child contact and later psychological distress and conflict in romantic relationships are mediated by perceived social support. Self-reported longitudinal data from a sample of incarcerated men who participated in a fatherhood education program (n = 2,096) were analyzed using structural equation modeling. Variables were assessed pre- and post-program participation. As hypothesized, more frequent child contact was associated with greater perceived social support, which predicted reduced psychological distress and reduced partner conflict. There were significant indirect effects of child contact on psychological distress and partner conflict via perceived social support. The findings may inform policies aiming to help incarcerated fathers to better manage psychological distress and conflictual relationships, preparing them for a more successful return to society.

2.
Proc Natl Acad Sci U S A ; 121(23): e2400727121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38819998

RESUMO

Understanding the interplay between charge, nematic, and structural ordering tendencies in cuprate superconductors is critical to unraveling their complex phase diagram. Using pump-probe time-resolved resonant X-ray scattering on the (0 0 1) Bragg peak at the Cu [Formula: see text] and O [Formula: see text] resonances, we investigate nonequilibrium dynamics of [Formula: see text] nematic order and its association with both charge density wave (CDW) order and lattice dynamics in La[Formula: see text]Eu[Formula: see text]Sr[Formula: see text]CuO[Formula: see text]. The orbital selectivity of the resonant X-ray scattering cross-section allows nematicity dynamics associated with the planar O 2[Formula: see text] and Cu 3[Formula: see text] states to be distinguished from the response of anisotropic lattice distortions. A direct time-domain comparison of CDW translational-symmetry breaking and nematic rotational-symmetry breaking reveals that these broken symmetries remain closely linked in the photoexcited state, consistent with the stability of CDW topological defects in the investigated pump fluence regime.

3.
DNA Repair (Amst) ; 133: 103611, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103522

RESUMO

WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase potential as a single agent chemotherapeutic, a better understanding of genetic alterations that impact cellular responses to WEE1 inhibition is warranted. Here, we investigate the impact of loss of the helicase, FBH1, on the cellular response to WEE1 inhibition. FBH1-deficient cells have a reduction in ssDNA and double strand break signaling indicating FBH1 is required for induction of replication stress response in cells treated with WEE1 inhibitors. Despite the defect in the replication stress response, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe. We propose loss of FBH1 is resulting in replication-associated damage that requires the WEE1-dependent G2 checkpoint for repair.


Assuntos
Proteínas de Ciclo Celular , DNA Helicases , Proteínas de Ciclo Celular/metabolismo , DNA Helicases/metabolismo , Morte Celular , Transdução de Sinais , Mitose , Linhagem Celular Tumoral
4.
Nat Commun ; 14(1): 5852, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730824

RESUMO

Understanding the nature and origin of collective excitations in materials is of fundamental importance for unraveling the underlying physics of a many-body system. Excitation spectra are usually obtained by measuring the dynamical structure factor, S(Q, ω), using inelastic neutron or x-ray scattering techniques and are analyzed by comparing the experimental results against calculated predictions. We introduce a data-driven analysis tool which leverages 'neural implicit representations' that are specifically tailored for handling spectrographic measurements and are able to efficiently obtain unknown parameters from experimental data via automatic differentiation. In this work, we employ linear spin wave theory simulations to train a machine learning platform, enabling precise exchange parameter extraction from inelastic neutron scattering data on the square-lattice spin-1 antiferromagnet La2NiO4, showcasing a viable pathway towards automatic refinement of advanced models for ordered magnetic systems.

5.
Kidney Int ; 104(5): 995-1007, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37598857

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) resulting from pathogenic variants in PKD1 and PKD2 is the most common form of PKD, but other genetic causes tied to primary cilia function have been identified. Biallelic pathogenic variants in the serine/threonine kinase NEK8 cause a syndromic ciliopathy with extra-kidney manifestations. Here we identify NEK8 as a disease gene for ADPKD in 12 families. Clinical evaluation was combined with functional studies using fibroblasts and tubuloids from affected individuals. Nek8 knockout mouse kidney epithelial (IMCD3) cells transfected with wild type or variant NEK8 were further used to study ciliogenesis, ciliary trafficking, kinase function, and DNA damage responses. Twenty-one affected monoallelic individuals uniformly exhibited cystic kidney disease (mostly neonatal) without consistent extra-kidney manifestations. Recurrent de novo mutations of the NEK8 missense variant p.Arg45Trp, including mosaicism, were seen in ten families. Missense variants elsewhere within the kinase domain (p.Ile150Met and p.Lys157Gln) were also identified. Functional studies demonstrated normal localization of the NEK8 protein to the proximal cilium and no consistent cilia formation defects in patient-derived cells. NEK8-wild type protein and all variant forms of the protein expressed in Nek8 knockout IMCD3 cells were localized to cilia and supported ciliogenesis. However, Nek8 knockout IMCD3 cells expressing NEK8-p.Arg45Trp and NEK8-p.Lys157Gln showed significantly decreased polycystin-2 but normal ANKS6 localization in cilia. Moreover, p.Arg45Trp NEK8 exhibited reduced kinase activity in vitro. In patient derived tubuloids and IMCD3 cells expressing NEK8-p.Arg45Trp, DNA damage signaling was increased compared to healthy passage-matched controls. Thus, we propose a dominant-negative effect for specific heterozygous missense variants in the NEK8 kinase domain as a new cause of PKD.


Assuntos
Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Animais , Humanos , Recém-Nascido , Camundongos , Proteínas de Transporte/metabolismo , Cílios/patologia , Rim/metabolismo , Mutação , Quinases Relacionadas a NIMA/genética , Quinases Relacionadas a NIMA/metabolismo , Doenças Renais Policísticas/genética , Rim Policístico Autossômico Dominante/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Serina/genética , Serina/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo
6.
BMJ Open ; 13(4): e068754, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019491

RESUMO

OBJECTIVES: Our aim was to examine wireless physical activity monitor (WPAM) use and its associations with contextual factors (age, highest education level, social support and mental health) among adults living with HIV engaged in a community-based exercise (CBE) intervention. DESIGN: Quantitative, longitudinal, observational study. SETTING: Toronto YMCA, Ontario, Canada. PARTICIPANTS: Eighty adults living with HIV who initiated the CBE intervention. INTERVENTION: Participants received a WPAM to track physical activity during a 25-week CBE intervention involving thrice-weekly exercise, supervised weekly (phase 1) and a 32-week follow-up involving thrice-weekly exercise with no supervision (phase 2), completed in December 2018. OUTCOME MEASURES: Uptake was measured as participants who consented to WPAM use at initation of the intervention. Usage was defined as the proportion of days each participant had greater than 0 steps out of the total number of days in the study. We measured contextual factors using a baseline demographic questionnaire (age, highest education level), and median scores from the bimonthly administered Medical Outcomes Study-Social Support Scale and Patient Health Questionnaire (mental health), where higher scores indicated greater social support and mental health concerns, respectively. We calculated Spearman correlations between WPAM usage and contextual factors. RESULTS: Seventy-six of 80 participants (95%) consented to WPAM use. In phase 1, 66% of participants (n=76) and in phase 2, 61% of participants (n=64) used the WPAM at least 1 day. In phase 1, median WPAM usage was 50% (25th, 75th percentile: 0%, 87%; n=76) of days enrolled and in phase 2, 23% (0%, 76%; n=64) of days. Correlation coefficients with WPAM usage ranged from weak for age (ρ=0.26) and mental health scores (ρ=-0.25) to no correlation (highest education level, social support). CONCLUSIONS: Most adults living with HIV consented to WPAM use, however, usage declined over time from phase 1 to phase 2. Future implementation of WPAMs should consider factors to promote sustained usage by adults living with HIV. TRIAL REGISTRATION NUMBER: NCT02794415.


Assuntos
Exercício Físico , Infecções por HIV , Humanos , Adulto , Inquéritos e Questionários , Ontário , Infecções por HIV/psicologia , Terapia por Exercício
7.
Fam Process ; 62(2): 653-670, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35655389

RESUMO

Little research has examined the potential spillover of parenting difficulties in the coparental stepfamily subsystem. Using family systems theory as a guide, we longitudinally examined: (a) whether early parenting difficulties within stepfamilies persist 1 year later and (b) whether the parenting difficulties experienced by one partner impact the parenting difficulties of the other partner within remarriages. Copies of marriage licenses were used to identify remarried individuals. Surveys were mailed out, with follow-up surveys mailed a year later, resulting in a sample of 676 remarried couples (the majority of which were White and college educated). The sample was split into three groups, according to stepfamily constellation: (a) families with a stepfather and biological mother; (b) families with a biological father and a stepmother; and (c) families with both stepfathers and stepmothers. We estimated three different actor-partner interdependence models (APIM), one for each group. Consistent with family systems theory, our findings showed that parenting and stepparenting difficulties were interrelated, though gendered in effect. All parenting and stepparenting difficulties displayed actor effects, suggesting that parenting difficulties persist 1 year later. However, the only cross-spouse influences (partner effects) were such that the mother's parenting difficulties (of her own biological children) were predicted by the father's parenting and stepparenting difficulties, and these differed by stepfamily constellation. Implications regarding gendered expectations, the importance of the coparenting subsystem in stepfamilies, early establishment of parental boundaries, and the (potentially important) inclusion of the stepfather in the parenting dynamics are discussed.


Assuntos
Estrutura Familiar , Poder Familiar , Masculino , Criança , Feminino , Humanos , Pais , Pai , Mães
8.
Front Chem ; 10: 997147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329859

RESUMO

This paper is part of a growing body of research work looking at the synthesis of an optimal adsorbent for the capture and containment of aqueous radioiodine from nuclear fuel reprocessing waste. 32 metalated commercial ion exchange resins were subjected to a two-tier screening assessment for their capabilities in the uptake of iodide from aqueous solutions. The first stage determined that there was appreciable iodide capacity across the adsorbent range (12-220 mg·g-1). Candidates with loading capacities above 40 mg·g-1 were progressed to the second stage of testing, which was a fractional factorial experimental approach. The different adsorbents were treated as discrete variables and concentrations of iodide, co-contaminants and protons (pH) as continuous variables. This gave rise to a range of extreme conditions, which were representative of the industrial challenges of radioiodine abatement. Results were fitted to linear regression models, both for the whole dataset (R 2 = 59%) and for individual materials (R 2 = 18-82%). The overall model determined that iodide concentration, nitrate concentration, pH and interactions between these factors had significant influences on the uptake. From these results, the top six materials were selected for project progression, with others discounted due to either poor uptake or noticeable iodide salt precipitation behaviour. These candidates exhibited reasonable iodide uptake in most experimental conditions (average of >20 mg·g-1 hydrated mass), comparing favourably with literature values for metallated adsorbents. Ag-loaded Purolite S914 (thiourea functionality) was the overall best-performing material, although some salt precipitation was observed in basic conditions. Matrix effects not withstanding it is recommended that metalated thiourea, bispicolylamine, and aminomethylphosphonic acid functionalized silicas warrant further exploration.

9.
Struct Dyn ; 9(5): 054302, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36276194

RESUMO

X-ray free electron laser experiments have brought unique capabilities and opened new directions in research, such as creating new states of matter or directly measuring atomic motion. One such area is the ability to use finely spaced sets of coherent x-ray pulses to be compared after scattering from a dynamic system at different times. This enables the study of fluctuations in many-body quantum systems at the level of the ultrafast pulse durations, but this method has been limited to a select number of examples and required complex and advanced analytical tools. By applying a new methodology to this problem, we have made qualitative advances in three separate areas that will likely also find application to new fields. As compared to the "droplet-type" models, which typically are used to estimate the photon distributions on pixelated detectors to obtain the coherent x-ray speckle patterns, our algorithm achieves an order of magnitude speedup on CPU hardware and two orders of magnitude improvement on GPU hardware. We also find that it retains accuracy in low-contrast conditions, which is the typical regime for many experiments in structural dynamics. Finally, it can predict photon distributions in high average-intensity applications, a regime which up until now has not been accessible. Our artificial intelligence-assisted algorithm will enable a wider adoption of x-ray coherence spectroscopies, by both automating previously challenging analyses and enabling new experiments that were not otherwise feasible without the developments described in this work.

10.
PLoS One ; 17(5): e0268191, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522625

RESUMO

Assessing levels of aggression-specifically reactive violence-has been a challenge in the past, since individuals might be reluctant to self-report aggressive tendencies. Furthermore, experimental studies often lack ecological validity. Immersive Virtual Reality (IVR) offers a reliable, ethically safe environment, and is the most realistic virtual simulation method currently available. It allows researchers to test participants' aggressive responses to realistic provocations from virtual humans. In the current study, 116 participants completed our IVR aggression task, in which they encountered avatars who would either approach them in a friendly or provocative fashion. Participants had the option either to shake hands or hit the virtual human, in congruent and incongruent trials. In congruent trials, the response required of the participant matched the approach with the avatar (e.g., hitting the avatar after provocation). In incongruent trials there was a mismatch between the avatars approach and the participants required response. Congruent trials were designed to measure the immediate reaction towards the virtual human, and incongruent trials to assess response inhibition. Additionally, participants also completed traditional questionnaire-based measures of aggression, as well as reporting their past violent behaviour. We found that the immediate aggressive responses in the IVR task correlated with the established questionnaire measures (convergent validity), and we found that the IVR task was a stronger predictor of past violent behaviour than traditional measures (discriminant validity). This suggests that IVR might be an effective way to assess aggressive behaviour in a more indirect, but realistic manner, than current questionnaire assessment.


Assuntos
Realidade Virtual , Simulação por Computador , Humanos , Inquéritos e Questionários , Violência
11.
Sci Rep ; 12(1): 3253, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228548

RESUMO

X-ray Free Electron Lasers provide femtosecond x-ray pulses with narrow bandwidth and unprecedented peak brightness. Special modes of operation have been developed to deliver double pulses for x-ray pump, x-ray probe experiments. However, the longest delay between the two pulses achieved with existing single bucket methods is less than 1 picosecond, thus preventing the exploration of longer time-scale dynamics. We present a novel two-bucket scheme covering delays from 350 picoseconds to hundreds of nanoseconds in discrete steps of 350 picoseconds. Performance for each pulse can be similar to the one in a single pulse operation. The method has been experimentally tested with the Linac Coherent Light Source (LCLS-I) and the copper linac with LCLS-II hard x-ray undulators.

12.
Gynecol Oncol ; 165(3): 610-618, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35351333

RESUMO

OBJECTIVE: Personalised care requires the identification of modifiable risk factors so that interventions can be implemented rapidly following a gynaecological cancer diagnosis. Our objective was to determine what pre-treatment factors are associated with quality of life (QOL) at baseline (pre-treatment) and 12 months. METHODS: 1222 women with a confirmed diagnosis of endometrial, ovarian, cervical or vulvar cancer from 82 UK NHS hospitals agreed to complete questionnaires at baseline, three and 12 months. Questionnaires included measures of QOL, health, lifestyle, support and self-management. The primary outcome measure was QOL as measured by Quality of Life in Adult Cancer Survivors (QLACS). Sites provided clinical data at baseline, six and 12 months. Linear regression models were constructed to examine the association between baseline characteristics and QOL outcomes. RESULTS: QOL declined between baseline and 3 months, followed by an improvement at 12 months. Baseline (pre-treatment) factors associated with worse QOL at both baseline and 12 months were depression, anxiety, living in a more deprived area and comorbidities which limit daily activities, whereas higher self-efficacy and age of 50+ years were associated with better QOL. CONCLUSIONS: Depression, anxiety and self-efficacy are modifiable risk factors that can impact on QOL. Screening for these, and assessment of whether comorbidities limit daily activities, should be incorporated in a holistic needs assessment and interventions to improve self-efficacy should be made available. Care can then be personalised from the outset to enable all women with a gynaecological cancer the opportunity to have the best QOL.


Assuntos
Neoplasias dos Genitais Femininos , Qualidade de Vida , Adulto , Ansiedade/etiologia , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/terapia , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Reino Unido
13.
Front Psychol ; 13: 1056180, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36687913

RESUMO

Introduction: Economic distress and the relationship stability of remarried couples has been subject to some exploration, but less emphasis has been placed on how economic distress among remarried couples impacts other relationship domains, particularly sexual intimacy. Methods: Through the lens of multidimensional family development theory (MFDT), this study utilizes longitudinal data over a three-year period to examine the links between economic distress, couple engagement, relationship satisfaction, and perceptions of sexual intimacy among remarried couples (n = 1,161 couples; 97% White). Results: Through a dyadic structural equation model, results showed that wives' report of economic distress was directly related to their self-rejection of a partner's sexual advances. Findings also revealed gender differences in how both relationship satisfaction and couple engagement influenced one to accept or reject their partner's sexual advances, with couple engagement acting as a significant predictor for wives. Relationship satisfaction was also found to explain (i.e., mediate) the relation between economic distress and sexual intimacy, but only for husbands. Discussion: Implications for further research and interventions designed to strengthen the relationships of remarried couples dealing with economic distress and intimacy issues are offered.

14.
Front Chem ; 10: 1043653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618856

RESUMO

Radioiodine capture and immobilization is not only important to consider during the operation of reactors (i.e., I-131), during nuclear accidents (i.e., I-131 and I-129) or nuclear fuel reprocessing (i.e., I-131 and I-129), but also during disposal of nuclear wastes (i.e., I-129). Most disposal plans for I-129-containing waste forms (including spent nuclear fuel) propose to store them in underground repositories. Here, iodine can be highly mobile and, given its radiotoxicity, needs to be carefully managed to minimize long-term environmental impacts arising from disposal. Typically, any process that has been used to capture iodine from reprocessing or in a reactor is not suitable for direct disposal, rather conversion into a wasteform for disposal is required. The objectives of these materials are to use either chemical immobilization or physical encapsulation to reduce the leaching of iodine by groundwaters. Some of the more recent ideas have been to design capture materials that better align with disposal concepts, making the industrial processing requirements easier. Research on iodine capture materials and wasteforms has been extensive. This review will act as both an update on the state of the research since the last time it was comprehensively summarized, and an evaluation of the industrial techniques required to create the proposed iodine wasteforms in terms of resulting material chemistry and applicability.

15.
Colorectal Dis ; 23(12): 3234-3250, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34679253

RESUMO

AIM: Depression experienced by people with colorectal cancer (CRC) is an important clinical problem affecting quality of life. Recognition of depression at key points in the pathway enables timely referral to support. This study aimed to examine depression before and 5 years after surgery to examine its prevalence and identify determinants. METHOD: The ColoREctal Wellbeing (CREW) study is a prospective UK cohort study involving 872 adults with nonmetastatic CRC recruited before surgery with curative intent. Questionnaires completed before surgery and 3, 9, 15, 24, 36, 48 and 60 months after surgery captured socio-demographics and assessed depression (Centre for Epidemiologic Studies Depression Scale, CES-D) and other psychosocial factors. Clinical details were also gathered. We present the prevalence of clinically significant depression (CES-D ≥ 20) over time and its predictors assessed before and 2 years after surgery. RESULTS: Before surgery, 21.0% of the cohort reported CES-D ≥ 20 reducing to 14.7% 5 years after surgery. Presurgery risk factors predicting subsequent depression were clinically significant depression and anxiety, previous mental health service use, low self-efficacy, poor health, having neoadjuvant treatment and low social support. Postsurgery risk factors at 2 years predicting subsequent depression were clinically significant depression, negative affect, cognitive dysfunction, accommodation type and poor health. CONCLUSION: Depression is highly pervasive in people with CRC, exceeding prevalence in the general population across follow-up. Our findings emphasize the need to screen and treat depression across the pathway. Our novel data highlight key risk factors of later depression at important and opportune time points: before surgery and at the end of routine surveillance. Early recognition and timely referral to appropriate support is vital to improve long-term psychological outcomes.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Adulto , Ansiedade , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Depressão/epidemiologia , Depressão/etiologia , Humanos , Prevalência , Estudos Prospectivos
16.
Artigo em Inglês | MEDLINE | ID: mdl-34360328

RESUMO

Research on morality has focused on differences in moral judgment and action. In this study, we investigated self-reported moral reasoning after a hypothetical moral dilemma was presented on paper, and moral reasoning after that very same dilemma was experienced in immersive virtual reality (IVR). We asked open-ended questions and used content analysis to determine moral reasoning in a sample of 107 participants. We found that participants referred significantly more often to abstract principles and consequences for themselves (i.e., it is against the law) after the paper-based moral dilemma compared to the IVR dilemma. In IVR participants significantly more often referred to the consequences for the people involved in the dilemma (i.e., not wanting to hurt that particular person). This supports the separate process theory, suggesting that decision and action might be different moral concepts with different foci regarding moral reasoning. Using simulated moral scenarios thus seems essential as it illustrates possible mechanisms of empathy and altruism being more relevant for moral actions especially given the physical presence of virtual humans in IVR.


Assuntos
Realidade Virtual , Empatia , Humanos , Julgamento , Princípios Morais , Resolução de Problemas
17.
J Phys Chem Lett ; 12(28): 6676-6683, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34260255

RESUMO

We demonstrate for the case of photoexcited [Ru(2,2'-bipyridine)3]2+ how femtosecond resonant inelastic X-ray scattering (RIXS) at the ligand K-edge allows one to uniquely probe changes in the valence electronic structure following a metal-to-ligand charge-transfer (MLCT) excitation. Metal-ligand hybridization is probed by nitrogen-1s resonances providing information on both the electron-accepting ligand in the MLCT state and the hole density of the metal center. By comparing to spectrum calculations based on density functional theory, we are able to distinguish the electronic structure of the electron-accepting ligand and the other ligands and determine a temporal upper limit of (250 ± 40) fs for electron localization following the charge-transfer excitation. The spin of the localized electron is deduced from the selection rules of the RIXS process establishing new experimental capabilities for probing transient charge and spin densities.

18.
Am J Physiol Heart Circ Physiol ; 320(3): H1136-H1155, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449851

RESUMO

Aging is associated with increased risk of cardiovascular and cerebrovascular events, which are preceded by early, negative remodeling of the vasculature. Low physical activity is a well-established risk factor associated with the incidence and development of disease. However, recent physical activity literature indicates the importance of considering the 24-h movement spectrum. Therefore, the purpose of this review was to examine the impact of the 24-h movement spectrum, specifically physical activity (aerobic and resistance training), sedentary behavior, and sleep, on cardiovascular and cerebrovascular outcomes in older adults, with a focus on recent evidence (<10 yr) and sex-based considerations. The review identifies that both aerobic training and being physically active (compared with sedentary) are associated with improvements in endothelial function, arterial stiffness, and cerebrovascular function. Additionally, there is evidence of sex-based differences in endothelial function: a blunted improvement in aerobic training in postmenopausal women compared with men. While minimal research has been conducted in older adults, resistance training does not appear to influence arterial stiffness. Poor sleep quantity or quality are associated with both impaired endothelial function and increased arterial stiffness. Finally, the review highlights mechanistic pathways involved in the regulation of vascular and cerebrovascular function, specifically the balance between pro- and antiatherogenic factors, which mediate the relationship between the 24-h movement spectrum and vascular outcomes. Finally, this review proposes future research directions: examining the role of duration and intensity of training, combining aerobic and resistance training, and exploration of sex-based differences in cardiovascular and cerebrovascular outcomes.


Assuntos
Ciclos de Atividade , Envelhecimento , Doenças Cardiovasculares/prevenção & controle , Remodelação Vascular , Fatores Etários , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/prevenção & controle , Feminino , Nível de Saúde , Estilo de Vida Saudável , Humanos , Masculino , Fatores de Proteção , Treinamento Resistido , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Comportamento Sedentário , Fatores Sexuais , Sono , Fatores de Tempo
19.
Opt Express ; 28(16): 23545-23553, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32752349

RESUMO

We design and realize an arrival time diagnostic for ultrashort X-ray pulses achieving unprecedented high sensitivity in the soft X-ray regime via cross-correlation with a ≈1550 nm optical laser. An interferometric detection scheme is combined with a multi-layer sample design to greatly improve the sensitivity of the measurement. We achieve up to 275% of relative signal change when exposed to 1.6 mJ/cm2 of soft X-rays at 530 eV, more than a hundred-fold improvement in sensitivity as compared to previously reported techniques. The resolution of the arrival time measurement is estimated to around 2.8 fs (rms). The demonstrated X-ray arrival time monitor paves the way for sub-10 fs-level timing jitter at high repetition rate X-ray facilities.

20.
Arterioscler Thromb Vasc Biol ; 39(10): 2168-2191, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31434495

RESUMO

OBJECTIVE: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-ß (tumor growth factor-ß), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. CONCLUSIONS: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.


Assuntos
Tecido Adiposo/irrigação sanguínea , Transição Epitelial-Mesenquimal/genética , Neovascularização Patológica/genética , Obesidade/genética , Fator de Crescimento Transformador beta1/farmacologia , Tecido Adiposo/metabolismo , Análise de Variância , Biomarcadores/metabolismo , Estudos de Casos e Controles , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Citometria de Fluxo/métodos , Humanos , Obesidade/fisiopatologia , Proteômica/métodos
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