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1.
BMC Public Health ; 24(1): 2570, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304869

RESUMO

BACKGROUND: Intensive lifestyle interventions were effective to reduce the risk of type 2 diabetes mellitus (T2DM) for women with gestational diabetes mellitus (GDM) history. However, reaching these mothers and maintaining participation in lifestyle interventions is suboptimal in real-world settings. Effective, feasible and sustainable new lifestyle interventions are needed. The objectives of this three-arm trial are to (1) compare diabetes risk outcomes of an evidence-based intensive lifestyle modification (ILSM) intervention, a camp-style lifestyle modification program (CAMP) intervention, and usual care among women with GDM history; and (2) evaluate the comparative efficacy of the CAMP versus ILSM intervention on implementation outcomes. METHODS: A three-arm cluster randomized clinical trial (RCT) using a hybrid type 2 implementation design will be conducted in two counties in Hunan province in China. Six towns from each county will be randomly selected and assigned to CAMP, ILSM, and the usual care group (25 women from each of 12 towns, 100 women in each arm). The ILSM includes six biweekly in-person sessions and 3-month telephone health consultations, while the CAMP consists of a 2-day camp-based session and 3-month health consultations via a popular social media platform. Both interventions share the same session content, including six lifestyle skills. Efficacy (T2DM risk score and behavioral, anthropometric, psychosocial, and glycemic variables) and implementation outcomes (recruitment, acceptability, feasibility, fidelity, and cost-effectiveness) will be collected at baseline, 6-month, and 12-month. Pre-planned ANOVA F-test and generalized estimating equations will be included to test time-by-arm interactions. DISCUSSION: The CAMP intervention is expected to have better reach, better attendance, and comparable effectiveness in reducing the risk of T2DM, thus improving postpartum care for GDM in China. The delivery of a concentrated format supplemented with technology-based support may provide an efficient and effective delivery model for implementing maternal health promotion programs in primary care settings. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200058150) on 31st March 2022.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , População Rural , Humanos , Feminino , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/prevenção & controle , Gravidez , China , Adulto , Comportamento de Redução do Risco , Ensaios Clínicos Controlados Aleatórios como Assunto , Estilo de Vida
2.
Thromb J ; 21(1): 30, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927371

RESUMO

BACKGROUND: Venous thromboembolism (VTE) including Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE), is a serious cause of patient morbidity and mortality in hospitals. Neurosurgical hospitalized patients have higher rates of immobility and bed rest, thus increasing their risk of developing VTE. This highlights the need for their thromboprophylaxis regimens. Patients' awareness of VTE is essential for promoting strategies such as early ambulation and encouraging self-assessment and self-reporting of VTE signs and symptoms. This study evaluated neurosurgical hospitalized patients' awareness of VTE and explored the influencing factors to provide a theoretical basis for nursing intervention. METHODS: We selected one tertiary level hospital in Hunan Province and randomly sampled eligible patients from each five neurosurgical units. We conducted a cross-sectional survey of the hospitalized patients of neurosurgery using the self-designed and validated VTE knowledge questionnaire, and the influencing factors were analyzed using SPSS 26.0. RESULTS: A total of 386 neurosurgical hospitalized patients completed the survey. The score of VTE knowledge in neurosurgical hospitalized patients was 13.22 (SD = 11.52). 36.0% and 21.2% of participants reported they had heard of DVT and PE, respectively. 38.9% of participants were unable to correctly identify any symptoms of VTE. The most frequently identified risk factor was 'immobility or bed rest for more than three days' (50.0% of participants), and 38.1% of patients agreed that PE could cause death. 29.5% of participants were unable to identify any prophylactic measures of VTE. The results of Negative Binomial Regression showed that the influencing factors of VTE knowledge in neurosurgical hospitalized patients were education level (P < 0.004) and sources of information related to VTE, including nurses (95% CI = 2.201-4.374, P < 0.001), and family member/friend (95% CI = 2.038-4.331, P < 0.001), Internet/TV (95% CI = 1.382-2.834, P < 0.001). Other sources included patient /pamphlet/poster /professional books (95% CI = 1.492-3.350, P < 0.001). CONCLUSIONS: This study demonstrates the lack of awareness of VTE among neurosurgical hospitalized patients. More attention must be paid to carrying out training on VTE knowledge according to different characteristics of neurosurgical hospitalized patients, so as to ensure safe and high-quality patient care.

3.
Global Health ; 19(1): 6, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703168

RESUMO

BACKGROUND: Many lifestyle interventions have demonstrated efficacy up to one-year follow-up, yet maintaining improvements at longer-term follow-up is a well-recognized worldwide challenge, especially in underserved areas. The purpose of this study is to compare the 18-month efficacy of an Intensive LifeStyle Modification Program to usual care in reducing the risk for type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM). METHODS: We conducted a two-arm, cluster randomized controlled trial among women with a history of GDM in China. A total of 16 towns (clusters) in two distinct rural areas in south-central China were randomly selected (8 towns per area) and assigned (1:1) to the intervention (Intensive LifeStyle Modification Program) or control (usual care) group with stratification in the two rural areas. The strategies for maintaining intervention effects were used (including setting recursive goals and providing a supportive environment, etc.) under the guidance of social cognitive theory. The primary outcome was a change in T2D risk; secondary outcomes included glycemic, weight-related, behavioral, and psychological variables. All outcomes were collected at baseline, 6, and 18 months. All participants entered the intention-to-treat analysis. Data were analyzed via generalized estimation equation models (accounting for clusters) at the individual level, with subgroup analysis included in the model. RESULTS: The sample included 320 women from 16 clusters (20 women per cluster). At 18 months, the intervention group demonstrated a significant improvement in T2D risk score, fasting blood glucose, body mass index (BMI), waist circumference, intention to eat low glycemic index food, perceived stress, quality of life in psychological and environmental domains, and social support over time (p < 0.05) based on the intention-to-treat analysis set. Subgroup analysis showed a significant interaction effect on T2D risk score in subgroups of different BMI, waist circumference, and blood glucose (p < 0.05). CONCLUSIONS: Over 18 months, the Intensive LifeStyle Modification Program reduced T2D risk among rural women with a history of GDM in China. Women who were overweight, had high abdominal adiposity, or had blood glucose intolerance benefited more from this intervention. This program serves as a potential diabetes prevention model for women with a history of GDM in low-resource settings worldwide. TRIAL REGISTRATION: Registered on Chinese Clinical Trial Registry (ChiCTR1800015023) on 1st March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25569.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Gravidez , Humanos , Feminino , Diabetes Mellitus Tipo 2/prevenção & controle , Glicemia , Qualidade de Vida , Diabetes Gestacional/prevenção & controle , Estilo de Vida
4.
BMC Psychiatry ; 22(1): 320, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513818

RESUMO

BACKGROUND: Gender differences have been found to be associated with individuals' pleasure. Cognitive flexibility and emotional expressivity might play an important role between gender differences and pleasure. This current study is to explore the mediating role of cognitive flexibility and emotional expressivity in the relationship between gender differences and pleasure. METHOD: In this cross-sectional study, a sample of 1107 full-time university students from five colleges in Tianjin, Chinese mainland was investigated by questionnaire. All participants completed the Temporal Experience of Pleasure Scale (TEPs), the Cognitive Flexibility Inventory (CFI), and the Berkeley Expressivity Questionnaire (BEQ). RESULTS: The results of independent T-test suggested that females reported better emotional expressivity, anticipatory pleasure and consummatory pleasure than males, whereas males had better cognitive flexibility than females. Using bootstrapping approach revealed that the partially mediation effects of cognitive flexibility on gender differences in anticipatory and consummatory pleasure, and that of emotional expressivity on gender differences in anticipatory and consummatory pleasure. Results of this present study stated that cognitive flexibility and emotional expressivity play a partial mediating role in explaining gender differences in anticipatory and consummatory pleasure. CONCLUSION: Females had higher anticipatory and consummatory pleasure because they tend to use emotional regulation strategy to express their emotion.


Assuntos
Cognição , Prazer , Anedonia/fisiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prazer/fisiologia , Fatores Sexuais , Inquéritos e Questionários
5.
Prev Sci ; 23(7): 1156-1168, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35773443

RESUMO

This study aimed to evaluate the efficacy of an intensive lifestyle modification program tailored to rural Chinese women with prior gestational diabetes mellitus compared with usual care. In a cluster randomized controlled trial, 16 towns (clusters) in two distinct rural areas in China were randomly selected (8 towns per district); and 320 women with prior gestational diabetes mellitus were recruited from these towns. With stratification for the two study districts, eight towns (160 women) were randomly assigned to the intervention group of a tailored intensive lifestyle modification program and 8 towns (160 women) to the control group. Process measures were collected on attendance, engagement, fidelity, and satisfaction. Primary efficacy outcomes included glycemic and weight-related outcomes, while secondary efficacy outcomes were behavioral outcomes and type 2 diabetes risk score, which were collected at baseline, 3-month, and 6-month follow-up. Generalized estimation equations were used to analyze the data. High attendance (72% of sessions), engagement (67% of interactive activities and group discussions), fidelity (98%), and satisfaction (92%) with the tailored intensive lifestyle modification program were achieved. There were significant reductions in fasting blood glucose, oral glucose tolerance test 2 h, waist circumference, and type 2 diabetes risk score of participants in the intervention group compared to the control group (p < .05). There was no significant intervention effect on body mass index or behavioral outcomes (p > .05). In this study, we demonstrate the successful efficacy of an Intensive Lifestyle Modification Program in reducing type 2 diabetes risk among younger women with prior gestational diabetes mellitus. This tailored program delivered by local healthcare providers is a promising approach for diabetes prevention in rural China, reducing health disparities in rural communities about diabetes prevention. Registered in the Chinese Clinical Trial Registry (ChiCTR2000037956) on 3rd Jan 2018.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Glicemia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/prevenção & controle , Feminino , Humanos , Estilo de Vida , Gravidez , População Rural
6.
Am J Physiol Lung Cell Mol Physiol ; 321(5): L859-L871, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524912

RESUMO

Alveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mitochondrial dysfunction including release of mitochondrial DNA (mtDNA) is a feature of senescence, which led us to investigate the role of the DNA-sensing guanine monophosphate-adenine monophosphate (GMP-AMP) synthase (cGAS) in IPF, with a focus on AEC senescence. cGAS expression in fibrotic tissue from lungs of patients with IPF was detected within cells immunoreactive for epithelial cell adhesion molecule (EpCAM) and p21, epithelial and senescence markers, respectively. Submerged primary cultures of AECs isolated from lung tissue of patients with IPF (IPF-AECs, n = 5) exhibited higher baseline senescence than AECs from control donors (Ctrl-AECs, n = 5-7), as assessed by increased nuclear histone 2AXγ phosphorylation, p21 mRNA, and expression of senescence-associated secretory phenotype (SASP) cytokines. Pharmacological cGAS inhibition using RU.521 diminished IPF-AEC senescence in culture and attenuated induction of Ctrl-AEC senescence following etoposide-induced DNA damage. Short interfering RNA (siRNA) knockdown of cGAS also attenuated etoposide-induced senescence of the AEC line, A549. Higher levels of mtDNA were detected in the cytosol and culture supernatants of primary IPF- and etoposide-treated Ctrl-AECs when compared with Ctrl-AECs at baseline. Furthermore, ectopic mtDNA augmented cGAS-dependent senescence of Ctrl-AECs, whereas DNAse I treatment diminished IPF-AEC senescence. This study provides evidence that a self-DNA-driven, cGAS-dependent response augments AEC senescence, identifying cGAS as a potential therapeutic target for IPF.


Assuntos
Células Epiteliais Alveolares/patologia , Senescência Celular/fisiologia , Dano ao DNA/genética , Fibrose Pulmonar Idiopática/patologia , Nucleotidiltransferases/metabolismo , Células A549 , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citocinas/biossíntese , DNA Mitocondrial/metabolismo , Desoxirribonuclease I/farmacologia , Molécula de Adesão da Célula Epitelial/metabolismo , Etoposídeo/farmacologia , Humanos , Mitocôndrias/genética , Mitocôndrias/patologia , Nucleotidiltransferases/antagonistas & inibidores , Nucleotidiltransferases/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais/fisiologia
7.
BMC Nurs ; 20(1): 122, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229667

RESUMO

BACKGROUND: Visual art training is a student-led approach using Western art pieces as the main teaching resources. It has been developed and applied in nursing and medical education in the United States. This study aimed to adapt visual art training to Chinese cultural context, then to compare the efficacy of the culturally-tailored visual art training versus traditional education on observational and diagnostic skills at 3-month follow-up among Chinese nursing students in master program. METHODS: This study included Phase 1 (cultural adaptation) and Phase 2 (3-month efficacy evaluation). It was conducted from June to September, 2019. In Phase 1, cultural barriers were identified and cultural adaptation strategy were made based on two focus group interviews. Phase 2 was a randomized controlled trial in a local museum. A total of 106 first-year nursing students in master program were randomized to the intervention group or the control group. Both groups received traditional education. In addition, intervention group received a visual art training (including a field-guided museum visit with observation and debriefing of Chinese oil paintings and clinical images, four teaching hours). Data were collected for both groups at baseline and 3-month follow-up on the observational and diagnostic skills measured by clinical image tests. Learning satisfaction with the visual art training was investigated among 53 intervention students and teaching satisfaction was done in 10 staff members by self-administered questionnaires. RESULTS: In phase 1, we adapted a culturally-tailored visual art training for nursing students in China. Observational skills of the intervention group increased significantly compared with the control group 3 months after the training (p < .001). A trend towards the improvement of diagnostic skills was indicated with increment of 2.92 points of the intervention group vs. 0.39 of the control group (p > .05). In general, all participants and staff were satisfied with the visual art training, especially the selected Chinese oil paintings and the student-led teaching process, but 34% (n = 18) were not satisfied with the long distance from the museum. CONCLUSIONS: A culturally-tailored visual art training with great acceptability and feasibility was implemented in China. It had a sustained positive effect on improving the observational skills of Chinese nursing students. This study can be used for a reference to introduce visual art training to nursing students or nurses from other cultures. TRIAL REGISTRATION: Retrospectively registered in Chinese Clinical Trial Registry ( ChiCTR2000037956 ) on 4th September, 2020.

8.
Clin Sci (Lond) ; 134(7): 889-905, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32219338

RESUMO

Senescence and mitochondrial stress are mutually reinforcing age-related processes that contribute to idiopathic pulmonary fibrosis (IPF); a lethal disease that manifests primarily in the elderly. Whilst evidence is accumulating that GMP-AMP synthase (cGAS) is crucial in perpetuating senescence by binding damaged DNA released into the cytosol, its role in IPF is not known. The present study examines the contributions of cGAS and self DNA to the senescence of lung fibroblasts from IPF patients (IPF-LFs) and age-matched controls (Ctrl-LFs). cGAS immunoreactivity was observed in regions of fibrosis associated with fibroblasts in lung tissue of IPF patients. Pharmacological inhibition of cGAS or its knockdown by silencing RNA (siRNA) diminished the escalation of IPF-LF senescence in culture over 7 days as measured by decreased p21 and p16 expression, histone 2AXγ phosphorylation and/or IL-6 production (P < 0.05, n = 5-8). The targeting of cGAS also attenuated etoposide-induced senescence in Ctrl-LFs (P < 0.05, n = 5-8). Levels of mitochondrial DNA (mDNA) detected by qPCR in the cytosol and medium of IPF-LFs or senescence-induced Ctrl-LFs were higher than Ctrl-LFs at baseline (P < 0.05, n = 5-7). The addition of DNAse I (100 U/ml) deaccelerated IPF-LF senescence (P < 0.05, n = 5), whereas ectopic mDNA or the induction of endogenous mDNA release augmented Ctrl-LF senescence in a cGAS-dependent manner (P < 0.05, n = 5). In conclusion, we provide evidence that cGAS reinforces lung fibroblast senescence involving damaged self DNA. The targeting of cGAS to supress senescent-like responses may have potential important therapeutic implications in the treatment of IPF.


Assuntos
Proliferação de Células , Senescência Celular , DNA Mitocondrial/metabolismo , Fibroblastos/enzimologia , Fibrose Pulmonar Idiopática/enzimologia , Pulmão/enzimologia , Nucleotidiltransferases/metabolismo , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Histonas/metabolismo , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Nucleotidiltransferases/antagonistas & inibidores , Nucleotidiltransferases/genética , Comunicação Parácrina , Fosforilação , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
MAGMA ; 33(4): 469-481, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31872356

RESUMO

OBJECTIVE: Tracking the migration of superparamagnetic iron oxide (SPIO)-labeled immune cells in vivo is valuable for understanding the immunogenic response to cancer and therapies. Quantitative cell tracking using TurboSPI-based R2* mapping is a promising development to improve accuracy in longitudinal studies on immune recruitment. However, off-resonance fat signal isochromats lead to modulations in the signal time-course that can be erroneously fit as R2* signal decay, overestimating the density of labeled cells, while excluding voxels with fat-typical modulations results in underestimation of cell density in voxels with mixed content. Approaches capable of accurate R2* estimation in the presence of fat are needed. METHODS: We propose a dual-decay (separate R2f* and R2w* for fat and water) Dixon-based signal model that accounts for the presence of fat in a voxel to provide better estimates of SPIO-induced dephasing. This model was tested in silico, in phantoms with varying quantities of fat and SPIO-labeled cells, and in 5 mice injected with SPIO-labeled CD8+ T cells. RESULTS: In silico single voxel simulations illustrate how the proposed dual-decay model provides stable R2w* estimates that are invariant to fat content. The proposed model outperforms previous methods when applied to in vitro samples of SPIO-labeled cells and oil prepared with oil content ≥ 15%. Preliminary in vivo results show that, compared to previous methods, the dual-decay model improves the balance of R2* mapping in fat-dense areas, which will yield more reliable analysis in future cell tracking studies. DISCUSSION: The proposed model is a promising tool for quantitative TurboSPI R2* cell tracking, with further refinements offering the possibility of better specificity and sensitivity.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Compostos Férricos/química , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Contagem de Células , Rastreamento de Células/métodos , Simulação por Computador , Meios de Contraste , Dextranos , Técnicas In Vitro , Nanopartículas de Magnetita , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Normal , Imagens de Fantasmas , Reprodutibilidade dos Testes , Água
10.
Clin J Sport Med ; 30(4): 366-371, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-29952843

RESUMO

OBJECTIVE: Evaluate the rate of concussions across Big 12 Conference football programs based on (1) equipment worn, (2) contact level, (3) preseason practice versus in-season practice versus games, and (4) mechanism of injury for concussion. DESIGN: Descriptive epidemiology study. SETTING: Big 12 Conference football practices and competitions. PATIENTS (OR PARTICIPANTS): Big 12 Conference football teams. ASSESSMENT OF RISK FACTORS: All Big 12 Conference institutions collected data on practice types, equipment worn, practice and game participation, and concussions during the fall, preseasons and regular seasons, from 2013 to 2016. MAIN OUTCOME MEASURES: Injury rates and injury rate ratios were reported with 95% confidence intervals (CIs). RESULTS: From 2013 to 2016, there were 375 concussions reported [0.98/1000 athlete exposures (AEs) (95% CI, 0.88-1.08)], an average of approximately 9 concussions per team per year. Concussion rates were highest in games (5.73/1000 AE), but among practices, concussion rates were highest in full-pad (1.18/1000 AEs) and live-contact (1.28/1000 AEs) practices. Concussion rates increased with increasing contact and equipment worn. Concussion rates were higher in the preseason than in the regular season, even when stratifying by contact level and equipment worn. CONCLUSIONS: Practice concussion rates are highest during fully padded and live-contact practices, supporting limitations on practice contact and equipment worn to reduce the risk associated with head-impact exposure. Higher concussion rates in the preseason and during games indicate an effect of play intensity on concussion risk, and further research is needed to evaluate the direct effect of practice contact level and equipment guidelines and restrictions on concussion incidence.


Assuntos
Concussão Encefálica/epidemiologia , Comportamento Competitivo , Futebol Americano/lesões , Condicionamento Físico Humano/efeitos adversos , Equipamentos de Proteção , Concussão Encefálica/etiologia , Concussão Encefálica/prevenção & controle , Humanos , Incidência , Masculino , Fatores de Risco , Estados Unidos/epidemiologia
11.
Nat Chem Biol ; 12(9): 755-62, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27454932

RESUMO

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling.


Assuntos
Diglicerídeos/metabolismo , Diglicerídeos/efeitos da radiação , Processos Fotoquímicos/efeitos da radiação , Proteína Quinase C/metabolismo , Proteína Quinase C/efeitos da radiação , Raios Ultravioleta , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos da radiação , Diglicerídeos/química , Camundongos , Fenômenos Ópticos , Proteína Quinase C/química , Transdução de Sinais/efeitos da radiação
12.
J Am Chem Soc ; 138(39): 12981-12986, 2016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27626130

RESUMO

Ceramide is a pro-apoptotic sphingolipid with unique physical characteristics. Often viewed as a second messenger, its generation can modulate the structure of lipid rafts. We prepared three photoswitchable ceramides, ACes, which contain an azobenzene photoswitch allowing for optical control over the N-acyl chain. Using combined atomic force and confocal fluorescence microscopy, we demonstrate that the ACes enable reversible switching of lipid domains in raft-mimicking supported lipid bilayers (SLBs). In the trans-configuration, the ACes localize into the liquid-ordered (Lo) phase. Photoisomerization to the cis-form triggers a fluidification of the Lo domains, as liquid-disordered (Ld) "lakes" are formed within the rafts. Photoisomerization back to the trans-state with blue light stimulates a rigidification inside the Ld phase, as the formation of small Lo domains. These changes can be repeated over multiple cycles, enabling a dynamic spatiotemporal control of the lipid raft structure with light.


Assuntos
Ceramidas/metabolismo , Luz , Microdomínios da Membrana/efeitos da radiação , Fenômenos Ópticos , Ceramidas/química , Isomerismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo
13.
Acc Chem Res ; 48(7): 1947-60, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26103428

RESUMO

Light is a fascinating phenomenon that ties together physics, chemistry, and biology. It is unmatched in its ability to confer information with temporal and spatial precision and has been used to map objects on the scale of tens of nanometers (10(-8) m) to light years (10(16) m). This information, gathered through super-resolution microscopes or space-based telescopes, is ultimately funneled through the human visual system, which is a miracle in itself. It allows us to see the Andromeda galaxy at night, an object that is 2.5 million light years away and very dim, and ski the next day in bright sunlight at an intensity that is 12 orders of magnitude higher. Human vision is only one of many photoreceptive systems that have evolved on earth and are found in all kingdoms of life. These systems rely on molecular photoswitches, such as retinal or tetrapyrrols, which undergo transient bond isomerizations or bond formations upon irradiation. The set of chromophores that have been employed in Nature for this purpose is surprisingly small. Nevertheless, they control a wide variety of biological functions, which have recently been significantly increased through the rapid development of optogenetics. Optogenetics originated as an effort to control neural function with genetically encoded photoreceptors that use abundant chromophores, in particular retinal. It now covers a variety of cellular functions other than excitability and has revolutionized the control of biological pathways in neuroscience and beyond. Chemistry has provided a large repertoire of synthetic photoswitches with highly tunable properties. Like their natural counterparts, these chromophores can be attached to proteins to effectively put them under optical control. This approach has enabled a new type of synthetic photobiology that has gone under various names to distinguish it from optogenetics. We now call it photopharmacology. Here we trace our involvement in this field, starting with the first light-sensitive potassium channel (SPARK) and concluding with our most recent work on photoswitchable fatty acids. Instead of simply providing a historical account of our efforts, we discuss the design criteria that guided our choice of molecules and receptors. As such, we hope to provide a roadmap to success in photopharmacology and make a case as to why synthetic photoswitches, properly designed and made available through well-planned and efficient syntheses, should have a bright future in biology and medicine.


Assuntos
Luz , Fototerapia , Humanos , Canais Iônicos/química , Canais Iônicos/metabolismo , Ligantes
14.
Int J Mol Sci ; 17(8)2016 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27472318

RESUMO

Non-typhoidal Salmonella enterica induces an early, short-lived pro-inflammatory response in chickens that is asymptomatic of clinical disease and results in a persistent colonization of the gastrointestinal (GI) tract that transmits infections to naïve hosts via fecal shedding of bacteria. The underlying mechanisms that control this persistent colonization of the ceca of chickens by Salmonella are only beginning to be elucidated. We hypothesize that alteration of host signaling pathways mediate the induction of a tolerance response. Using chicken-specific kinomic immune peptide arrays and quantitative RT-PCR of infected cecal tissue, we have previously evaluated the development of disease tolerance in chickens infected with Salmonella enterica serovar Enteritidis (S. Enteritidis) in a persistent infection model (4-14 days post infection). Here, we have further outlined the induction of an tolerance defense strategy in the cecum of chickens infected with S. Enteritidis beginning around four days post-primary infection. The response is characterized by alterations in the activation of T cell signaling mediated by the dephosphorylation of phospholipase c-γ1 (PLCG1) that inhibits NF-κB signaling and activates nuclear factor of activated T-cells (NFAT) signaling and blockage of interferon-γ (IFN-γ) production through the disruption of the JAK-STAT signaling pathway (dephosphorylation of JAK2, JAK3, and STAT4). Further, we measured a significant down-regulation reduction in IFN-γ mRNA expression. These studies, combined with our previous findings, describe global phenotypic changes in the avian cecum of Salmonella Enteritidis-infected chickens that decreases the host responsiveness resulting in the establishment of persistent colonization. The identified tissue protein kinases also represent potential targets for future antimicrobial compounds for decreasing Salmonella loads in the intestines of food animals before going to market.


Assuntos
Ceco/imunologia , Fosfotransferases/metabolismo , Doenças das Aves Domésticas/imunologia , Salmonelose Animal/imunologia , Salmonella enteritidis/patogenicidade , Animais , Ceco/metabolismo , Ceco/microbiologia , Galinhas , Fosfotransferases/genética , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/microbiologia , Análise Serial de Proteínas , Reação em Cadeia da Polimerase em Tempo Real , Salmonelose Animal/genética , Salmonelose Animal/microbiologia , Salmonella enteritidis/imunologia , Salmonella enteritidis/metabolismo , Transdução de Sinais , Análise Serial de Tecidos
15.
Heart Lung Circ ; 24(7): 667-72, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25862519

RESUMO

Levosimendan, a calcium sensitiser, has recently emerged as a valuable agent in the peri-operative management of cardiac surgery patients. Levosimendan is a calcium-sensitising ionodilator. By binding to cardiac troponin C and reducing its calcium-binding co-efficient, it enhances myofilament responsiveness to calcium and thus enhances myocardial contractility without increasing oxygen demand. Current evidence suggests that levosimendan enhances cardiac function after cardiopulmonary bypass in patients with both normal and reduced left ventricular function. In addition to being used as post-operative rescue therapy for low cardiac output syndrome, a pre-operative levosimendan infusion in high risk patients with poor cardiac function may reduce inotropic requirements, the need for mechanical support, the duration of intensive care admissions as well as post-operative mortality. Indeed, it is these higher-risk patients who may experience a greater degree of benefit. Larger, multicentre randomised trials in cardiac surgery will help to elucidate the full potential of this agent.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Hidrazonas/uso terapêutico , Assistência Perioperatória/métodos , Piridazinas/uso terapêutico , Feminino , Humanos , Hidrazonas/farmacocinética , Masculino , Miocárdio/metabolismo , Piridazinas/farmacocinética , Simendana , Função Ventricular Esquerda/efeitos dos fármacos
16.
Pain Med ; 15(10): 1647-56, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24506310

RESUMO

OBJECTIVE: Ultrasound (US)-guided pain procedures become increasingly important due to their numerous advantages. Solid proficiency is necessary, however, to minimize complications and guarantee adequate performance. To enable beginners to learn the relevant skills in the technique of US-guided stellate ganglion (SGB) and intercostal nerve block (ICB), a training curriculum was developed and tested using self-made phantoms. DESIGN: The curriculum comprised an introduction to the didactics of US, SGB, and ICB, a demonstration of the techniques by an expert user, as well as hands-on training of needle guidance using a gel pad and two phantoms. SUBJECTS: Three groups of participants with different levels of expertise with US-guided procedures took part in the curriculum: 12 medical students with no prior experience, 12 anesthesiologists with some experience, and five senior anesthesiologists who already applied these techniques on a regular basis. METHODS: Participants evaluated the curriculum via questionnaire, and their performance of time until adequate puncture, attempts required for adequate puncture, number of corrections, and unintentional punctures was assessed. RESULTS: The medical students significantly increased their speed during both nerve blocks and reduced the number of attempts and corrections necessary to perform adequate ICB. The anesthesiologists with some experience also increased their speed in both blocks. The participants rated the curriculum as good to very good. CONCLUSIONS: The combination of theoretical teaching, expert demonstration, and hands-on training on phantoms proved useful in acquiring skills needed for US-guided procedures such as SGB and ICB, and can potentially improve graduate and post-graduate medical education.


Assuntos
Competência Clínica , Educação Médica/métodos , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Competência Clínica/estatística & dados numéricos , Currículo , Humanos , Nervos Intercostais/cirurgia , Imagens de Fantasmas , Gânglio Estrelado/cirurgia
17.
J Psychoactive Drugs ; 46(5): 393-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25364991

RESUMO

Obsessive Compulsive Disorder (OCD) is a psychiatric disorder with considerable morbidity and mortality. This condition disables many individuals and is often refractory to treatment. Research suggests that serotonin plays a role in OCD symptom reduction. We present a case of an individual who successfully used psilocybin, a serotonergic agent, to reduce the core symptoms of OCD for several years. Although not endorsing this form of treatment, we feel that the successful use of this agent highlights the role of serotonergic factors in OCD and the need for further, legitimate research into the value of psilocybin in the treatment of anxiety disorders.


Assuntos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Psilocibina/uso terapêutico , Adulto , Humanos , Masculino
18.
J Cardiothorac Surg ; 19(1): 168, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566159

RESUMO

Cardiac leiomyosarcomas are a rare subset of the already infrequent, primary malignant cardiac neoplasia spectrum. The most common site for a primary leiomyosarcoma of the ventricle is on the right with fewer than five globally reported cases in the left ventricle. Most present with non-specific symptoms but attention is usually sought after the appearance of compressive symptoms or arrhythmias. We present a case of a left ventricular leiomyosarcoma in a 50-year old female patient that had a delayed diagnosis and its subsequent surgical resection and oncological management with docetaxel and gemcitabine. This case highlights the need for a high index of suspicion for cardiac masses especially if there are competing chronic diseases with similar symptomatology. Given the rare presentation of left ventricular leiomyosarcomas, case reports may provide valuable information that is otherwise unavailable.


Assuntos
Neoplasias Cardíacas , Leiomiossarcoma , Feminino , Humanos , Pessoa de Meia-Idade , Ventrículos do Coração/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/cirurgia , Leiomiossarcoma/patologia , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/patologia
19.
Psychol Res Behav Manag ; 17: 957-972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481598

RESUMO

Background: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes. Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes. Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention's effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software. Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(-1.31 to -0.32), p = 0.001], six months [95% CI=(-0.75 to -0.22), p = 0.0003], and 12 months [95% CI=(-0.72 to -0.24), <0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (-0.38 to -0.13), p < 0.0001] or more than six sessions [95% CI=(-1.76 to -0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (-0.57 to -0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (-1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (-1.27 to 0.27), p = 0.20] after intervention, compared to control group. Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.

20.
Microorganisms ; 11(4)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37110262

RESUMO

Poultry litter is a valuable crude protein feedstuff for ruminants, but it must be treated to kill pathogens before feeding. Composting effectively kills pathogens, but it risks losing ammonia to volatilization or leaching during degradation of uric acid and urea. Hops bitter acids also exert antimicrobial activity against certain pathogenic and nitrogen-degrading microbes. Consequently, the present studies were conducted to test if adding bitter acid-rich hop preparations to simulated poultry litter composts may improve nitrogen retention while simultaneously improving pathogen killing. Results from an initial study, testing doses of Chinook or Galena hops preparations designed to each deliver 79 ppm hops ß-acid, revealed that, after nine days simulated composting of wood chip litter, ammonia concentrations were 14% lower (p < 0.05) in Chinook-treated composts than untreated composts (13.4 ± 1.06 µmol/g). Conversely, urea concentrations were 55% lower (p < 0.05) in Galena-treated than untreated composts (6.2 ± 1.72 µmol/g). Uric acid accumulations were unaffected by hops treatments in this study but were higher (p < 0.05) after three days than after zero, six, or nine days of composting. In follow-up studies, Chinook or Galena hops treatments (delivering 2042 or 6126 ppm of ß-acid, respectively) for simulated composts (14 days) of wood chip litter alone or mixed 3:1 with ground Bluestem hay (Andropogon gerardii) revealed that these higher dosages had little effect on ammonia, urea, or uric acid accumulations when compared to untreated composts. Volatile fatty acid accumulations measured in these later studies were affected by the hops treatments, with butyrate accumulations being lower after 14 days in hops-treated composts than in untreated compost. In all studies, beneficial effects of Galena or Chinook hops treatments were not observed on the antimicrobial activity of the simulated composts, with composting by itself decreasing (p < 0.05) counts of select microbial populations by more than 2.5 log10 colony forming units/g compost dry matter. Thus, while hops treatments had little effect on pathogen control or nitrogen retention within the composted litter, they did lessen accumulations of butyrate, which may prevent adverse effects of this fatty acid on palatability of litter fed to ruminants.

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