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1.
PLoS One ; 19(4): e0299825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593174

RESUMO

Chilling sensitivity is one of the greatest challenges affecting the marketability and profitability of sweet basil (Ocimum basilicum L.) in the US and worldwide. Currently, there are no sweet basils commercially available with significant chilling tolerance and traditional aroma profiles. This study was conducted to identify quantitative trait loci (QTLs) responsible for chilling tolerance and aroma compounds in a biparental mapping population, including the Rutgers advanced breeding line that served as a chilling tolerant parent, 'CB15', the chilling sensitive parent, 'Rutgers Obsession DMR' and 200 F2 individuals. Chilling tolerance was assessed by percent necrosis using machine learning and aroma profiling was evaluated using gas chromatography (GC) mass spectrometry (MS). Single nucleotide polymorphism (SNP) markers were generated from genomic sequences derived from double digestion restriction-site associated DNA sequencing (ddRADseq) and converted to genotype data using a reference genome alignment. A genetic linkage map was constructed and five statistically significant QTLs were identified in response to chilling temperatures with possible interactions between QTLs. The QTL on LG24 (qCH24) demonstrated the largest effect for chilling response and was significant in all three replicates. No QTLs were identified for linalool, as the population did not segregate sufficiently to detect this trait. Two significant QTLs were identified for estragole (also known as methyl chavicol) with only qEST1 on LG1 being significant in the multiple-QTL model (MQM). QEUC26 was identified as a significant QTL for eucalyptol (also known as 1,8-cineole) on LG26. These QTLs may represent key mechanisms for chilling tolerance and aroma in basil, providing critical knowledge for future investigation of these phenotypic traits and molecular breeding.


Assuntos
Ocimum basilicum , Locos de Características Quantitativas , Humanos , Ocimum basilicum/genética , Melhoramento Vegetal , Mapeamento Cromossômico/métodos , Fenótipo , Genômica , Polimorfismo de Nucleotídeo Único , Ligação Genética
2.
J Health Psychol ; : 13591053241248283, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679895

RESUMO

Limited research has explored the relationship between self-determination theory constructs (basic psychological needs, autonomous/controlled regulation) and internalized weight stigma (IWS). This cross-sectional, online study surveyed 480 U.S. women aged 18-40 between 2021 and 2022. We hypothesized that need frustration and controlled weight regulation would relate to higher IWS, which would be associated with dysfunctional eating, distress, and lower life satisfaction. Conversely, we predicted that need satisfaction, autonomous regulation, and body satisfaction would be associated with reduced IWS, dysfunctional eating and distress, and higher life satisfaction. Structural equation modeling demonstrated an acceptable model fit (CMIN/DF = 2.95, CFI = 0.90, RMSEA = 0.06, SRMR = 0.07), accounting for 74% of IWS variance. Findings indicate the relevance of self-determination theory in understanding IWS, supporting a dual-process model whereby adverse and adaptive outcomes follow distinct pathways. Longitudinal studies are warranted to validate psychological needs and regulatory styles as mechanisms for IWS development and to assess generalizability across diverse populations.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38634862

RESUMO

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3-7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.

4.
J Sleep Res ; : e14193, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485134

RESUMO

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised-controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition. A total of 46 unmedicated nurses suffering from shift work disorder with insomnia (age: 39.7 ± 12.1 years; 80.4% female) were randomised to the SleepCare group or the waitlist control group. The primary outcome measure was the Insomnia Severity Index. Other questionnaires on sleep, mental health and occupational functioning, sleep diary data and actigraphy data were analysed as secondary outcomes. Assessments were conducted before (T0), after the intervention/waitlist period (T1), and 6 months after treatment completion (T2). The SleepCare group showed a significant reduction in insomnia severity from T0 to T1 compared with the control condition (ß = -4.73, SE = 1.12, p < 0.001). Significant improvements were observed in sleepiness, dysfunctional beliefs about sleep, pre-sleep arousal, sleep effort, self-reported sleep efficiency and sleep onset latency. No significant effect was found in actigraphy data. Depressive and anxiety symptoms, cognitive irritation and work ability improved significantly. Overall, satisfaction and engagement with the intervention was high. SleepCare improved insomnia severity, sleep, mental health and occupational functioning. This is the first randomised-controlled trial investigating the efficacy of digital cognitive behavioural therapy for insomnia in a population suffering from shift work disorder with insomnia. Future research should further explore these effects with larger sample sizes and active control conditions.

5.
Semin Arthritis Rheum ; 66: 152423, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38460282

RESUMO

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.


Assuntos
Consenso , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Reumatologia , Humanos , Reumatologia/normas , Doenças Reumáticas
6.
Semin Arthritis Rheum ; 66: 152422, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461757

RESUMO

OBJECTIVE: To increase awareness and understanding of the principles of Equity, Diversity, and Inclusivity (EDI) within Outcome Measures in Rheumatology's (OMERACT) members. For this, we aimed to obtain ideas on how to promote and foster these principles within the organization and determine the diversity of the current membership in order to focus future efforts. METHODS: We held a plenary workshop session at OMERACT 2023 with roundtable discussions on barriers and solutions to increased diversity within OMERACT. We conducted an anonymous, web-based survey of members to record characteristics including population group, gender identity, education level, age, and ability. RESULTS: The workshop generated ideas to increase diversity of participants across the themes of building relationships [12 topics], materials and methods [5 topics], and conference-specific [6 topics]. Four hundred and seven people responded to the survey (25 % response rate). The majority of respondents were White (75 %), female (61 %), university-educated (94 %), Christian (42 %), spoke English at home (60 %), aged 35 to 55 years (50 %), and did not report a disability (64 %). CONCLUSION: OMERACT is committed to improving its diversity. Next steps include strategic recruitment of members to the EDI working group, drafting an EDI mission statement centering equity and inclusivity in the organization, and developing guidance for the OMERACT Handbook to help all working groups create actionable plans for promoting EDI principles.


Assuntos
Diversidade Cultural , Reumatologia , Humanos , Feminino , Masculino , Sociedades Médicas , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários
7.
Ecol Evol ; 14(2): e11017, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362164

RESUMO

California's Channel Islands are home to two endemic mammalian carnivores: island foxes (Urocyon littoralis) and island spotted skunks (Spilogale gracilis amphiala). Although it is rare for two insular terrestrial carnivores to coexist, these known competitors persist on both Santa Cruz Island and Santa Rosa Island. We hypothesized that examination of their gut microbial communities would provide insight into the factors that enable this coexistence, as microbial symbionts often reflect host evolutionary history and contemporary ecology. Using rectal swabs collected from island foxes and island spotted skunks sampled across both islands, we generated 16S rRNA amplicon sequencing data to characterize their gut microbiomes. While island foxes and island spotted skunks both harbored the core mammalian microbiome, host species explained the largest proportion of variation in the dataset. We further identified intraspecific variation between island populations, with greater differentiation observed between more specialist island spotted skunk populations compared to more generalist island fox populations. This pattern may reflect differences in resource utilization following fine-scale niche differentiation. It may further reflect evolutionary differences regarding the timing of intraspecific separation. Considered together, this study contributes to the growing catalog of wildlife microbiome studies, with important implications for understanding how eco-evolutionary processes enable the coexistence of terrestrial carnivores-and their microbiomes-in island environments.

8.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338955

RESUMO

Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst. Since controlled oxygen tension is determinant for achieving normal implantation and placentation and a chronic hypoxic environment leads to shallow trophoblast invasion, we evaluated if FOXM1 expression changes in response to different oxygen tensions in the HTR-8/SVneo first trimester human trophoblast cell line and observed that FOXM1 expression was significantly higher when trophoblast cells were cultured at 3% O2, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O2 that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O2 and 1% O2, respectively, in HTR-8/SVneo cells. FOXM1 overexpression increased transmigration ability and tubule formation. Using a 3D trophoblast invasion model with trophospheres from HTR-8/SVneo cells cultured on a layer of MATRIGEL and of mesenchymal stem cells isolated from menstrual fluid, we observed that trophospheres obtained from 3D trophoblast invasion displayed higher FOXM1 expression compared with pre-invasion trophospheres. Moreover, we have also observed that FOXM1-overexpressing trophospheres increased trophoblast invasion compared with controls. HTR-8/SVneo-FOXM1-depleted cells led to a downregulation of PLK4, VEGF, and MMP2 mRNA expression. Our current findings suggest that FOXM1 participates in embryo implantation by contributing to trophoblast migration and early trophoblast invasion, by inducing transcription activation of genes involved in these processes. Maternal-fetal communication is crucial for trophoblast invasion, and maternal stromal cells may induce higher levels of FOXM1 in trophoblast cells.


Assuntos
Proteína Forkhead Box M1 , Placenta , Trofoblastos , Animais , Feminino , Humanos , Camundongos , Gravidez , Ratos , Movimento Celular , Implantação do Embrião , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Oxigênio/metabolismo , Placenta/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Trofoblastos/metabolismo
9.
J Dev Behav Pediatr ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38347666

RESUMO

BACKGROUND AND OBJECTIVES: Neighborhood socioeconomic disadvantage is associated with lower neurocognitive scores and differences in brain structure among school-age children. Associations between positive neighborhood characteristics, infant brain activity, and cognitive development are underexplored. We examined direct and indirect associations between neighborhood opportunity, brain activity, and cognitive development. METHODS: This longitudinal cohort study included infants from 2 primary care clinics in Boston and Los Angeles. Using a sample of 65 infants, we estimated path models to examine associations between neighborhood opportunity (measured by the Child Opportunity Index), infant electroencephalography (EEG) at 6 months, and infant cognitive development (measured using the Mullen Scales of Early Learning) at 12 months. A mediation model tested whether EEG power explained associations between neighborhood opportunity and infant cognition. RESULTS: Neighborhood opportunity positively predicted infant absolute EEG power across multiple frequency bands: low (b = 0.12, 95% CI 0.01-0.24, p = 0.04, = 0.21); high (b = 0.11, 95% CI 0.01-0.21, p = 0.03, = 0.23); (b = 0.10, 95% CI 0.00-0.19, p = 0.04, = 0.20); and (b = 0.12, 95% CI 0.02-0.22, p = 0.02, = 0.24). The results remained statistically significant after applying a Benjamini-Hochberg false discovery rate of 0.10 to adjust for multiple comparisons. No significant associations emerged between neighborhood opportunity, relative EEG power, and infant cognition. Mediation was not significant. CONCLUSION: Neighborhood opportunity is positively associated with some forms of infant brain activity, suggesting that positive neighborhood characteristics may play a salient role in early development.

10.
Semin Arthritis Rheum ; 65: 152381, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38306813

RESUMO

OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.


Assuntos
Reumatologia , Humanos , Consenso , Tomada de Decisão Compartilhada , Avaliação de Resultados em Cuidados de Saúde
11.
Artigo em Inglês | MEDLINE | ID: mdl-38218997

RESUMO

Embedding mental health and wellbeing programs within youth sports development programs can help provide more young people with mental health support. However, delivering such programs in multiple locations across metropolitan, regional, and rural areas requires novel solutions to overcome geographic and logistical barriers. We examined the delivery of an integrated system delivered within an Australian junior rugby league program. The program included online assessment and feedback about youth mental health, as well as connection with evidence-informed resources and referral sources via parent telephone and email support. There were four methods of delivering player workshops during training sessions: (a) In-person Delivery Only, (b) In-person + Remote Real-time (video-conferenced), (c) In-person + Remote Prerecorded (video-recorded), and (d) Remote Delivery Only (video-conferenced and/or video-recorded). In-person delivered player workshops were facilitated by local rugby league personnel. Remote delivered workshops were facilitated by psychologists from the mental health research team. Participants were 671 boys (12-15 years; M age = 13.35; SD = 0.35) in 21 metropolitan, regional and rural locations. Regardless of delivery condition, players with elevated anxiety, depression and behavioural problems reported significant declines in symptoms from pre- to post-program, and those within healthy ranges did not change from pre- to post-program. Player workshop enjoyment ratings were higher in the In-person + Remote Real-time condition and the Remote Delivery Only condition than the In-person Delivery Only condition. However, non-completion of the post-program assessment across all conditions was higher than in prior studies and a comparison group of players who did not complete the program was not included. Mental health benefits may be observed across in-person and remote modes of delivering mental health workshops within youth sports programs. However, the involvement of mental health personnel, whether in-person or remotely, and mixed delivery modes, may be important for young people's retention and satisfaction.

12.
J Allergy Clin Immunol Glob ; 3(1): 100192, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38187868

RESUMO

Background: The National Asthma Education and Prevention Program guidelines emphasize environmental control as an integral part of asthma management; however, limited national-level data exist on how clinicians implement environmental control recommendations. Objective: We analyzed data on clinicians' self-reported use of recommended environmental control practices in a nationally representative sample (n = 1645) of primary care physicians, asthma specialists, and advanced practice providers from the National Asthma Survey of Physicians, a supplemental questionnaire to the 2012 National Ambulatory Medical Care Survey. Methods: We examined clinician and practice characteristics as well as clinicians' decisions and strategies regarding environmental trigger assessment and environmental control across provider groups. Regression modeling was used to identify clinician and practice characteristics associated with implementation of guideline recommendations. Results: A higher percentage of specialists assessed asthma triggers at home, school, and/or work than primary care or advanced practice providers (almost always: 53.6% vs 29.4% and 23.7%, respectively, P < .001). Almost all clinicians (>93%) recommended avoidance of secondhand tobacco smoke, whereas recommendations regarding cooking appliances (eg, proper ventilation) were infrequent. Although assessment and recommendation practices differed between clinician groups, modeling results showed that clinicians who reported almost always assessing asthma control were 5- to 6-fold more likely to assess environmental asthma triggers. Use of asthma action plans was also strongly associated with implementation of environmental control recommendations. Conclusions: Environmental assessment and recommendations to patients varied among asthma care providers. High adherence to other key guideline components, such as assessing asthma control, was associated with environmental assessment and recommendation practices on environmental control.

13.
Acad Pediatr ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38278480

RESUMO

OBJECTIVE: Exposure to maternal stress in early childhood can increase risk for learning and behavior challenges. We sought to gain in-depth understanding of how mothers perceive stressors to impact child wellbeing and identify mothers' strategies for navigating stressors with their young children. METHODS: We recruited English- and Spanish-speaking mothers from a primary care clinic serving predominantly publicly insured children. Twenty-one mothers (aged >18 years) of children (aged 6-29 months) participated in in-depth, semi-structured interviews to discuss their experiences and beliefs regarding stress and parenting. Interviews were recorded, transcribed verbatim, and analyzed using the constant comparative method associated with a grounded theory approach. RESULTS: We developed the following hypothesized explanatory model based on our key thematic findings: Mothers described a dyadic model of stress, whereby both their children's and their own experiences of and responses to stressors are interdependent. Mothers use preventive and responsive buffering to mitigate the impact of stress on their children; however, their access to resources, including social and financial support, shapes their capacity for implementing such strategies. Affection and other forms of relational support may function to protect against the negative impacts of stress. CONCLUSION: In the setting of poverty-related chronic stressors, mothers play an active role in mitigating the impact of stress on their children's wellbeing through responsive caregiving. Policies aimed at reducing poverty-related stress exposures and experiences among low-income families may be key interventions for promoting responsive caregiving during a critical time in child development.

14.
Behav Res Ther ; 174: 104477, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281443

RESUMO

Fear conditioning is a common experimental paradigm for modelling the development, and exposure-based treatment, of anxiety disorders. Measures of fear such as threat-expectancy, physiological arousal, and fear ratings typically extinguish, however feared stimuli may still be evaluated negatively (i.e. retain negative valence). This systematic review provides the first investigation of the relationship between fear conditioning methodology and extinction of negative stimulus valence. Principal findings were that type of CS (conditioned stimulus) and the CS-US pairing (i.e. specific combination of CS and unconditioned stimulus) predicted extinction outcome. Extinction of absolute negative CS valence was always achieved with shape CSs; often achieved with low fear-relevant animals as CSs, and less frequently achieved with faces as CSs - particularly neutral faces paired with a shock US. Modified extinction procedures typically achieved the same outcome as standard extinction procedures, except for partially-reinforced extinction, which was less effective than standard extinction, and positive imagery training, which was more effective than standard extinction. Further studies are warranted to evaluate the influence of fear conditioning methodology on extinction of absolute negative CS valence.


Assuntos
Extinção Psicológica , Medo , Humanos , Extinção Psicológica/fisiologia , Medo/fisiologia , Condicionamento Clássico/fisiologia , Transtornos de Ansiedade , Condicionamento Operante
15.
Cells ; 13(2)2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38247865

RESUMO

Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the mechanistic link between adipogenicity and tumorigenicity in breast tissues is poorly understood. We used in vitro and in vivo approaches to investigate the mechanistic relationship between obesity and the onset and progression of breast cancer. In obesity, adipose tissue expansion and remodeling are associated with increased inflammatory mediator's release and anti-inflammatory mediators' reduction.. In order to mimic the obesity micro-environment, we cultured cells in an enriched pro-inflammatory cytokine medium to which we added a low concentration of beneficial adipokines. Epithelial cells exposed to the obesity micro-environment were phenotypically transformed into mesenchymal-like cells, characterized by an increase in different mesenchymal markers and the acquisition of the major hallmarks of cancerous cells; these include sustained DNA damage, the activation of the ATR-Chk2 pathway, an increase in proliferation rate, cell invasion, and resistance to conventional chemotherapy. Transcriptomic analysis revealed that several genes, including RhoJ, CCL7, and MMP9, acted as potential major players in the observed phenomenon. The transcriptomics findings were confirmed in vitro using qRT-PCR and in vivo using high-fat-diet-fed mice. Our data suggests RhoJ as a potential novel molecular driver of tumor development in breast tissues and a mediator of cell resistance to conventional chemotherapy through PAK1 activation. These data propose that RhoJ is a potential target for therapeutic interventions in obese breast cancer patients.


Assuntos
Neoplasias da Mama , Obesidade , Proteínas rho de Ligação ao GTP , Animais , Feminino , Humanos , Camundongos , Adipocinas , Adiposidade , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Obesidade/complicações , Microambiente Tumoral , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
16.
Nat Nanotechnol ; 19(4): 534-544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38168926

RESUMO

Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release. It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.


Assuntos
Hipoglicemia , Insulina , Ratos , Camundongos , Animais , Glicemia , Hipoglicemia/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos
17.
Semin Arthritis Rheum ; 64: 152340, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38071831

RESUMO

OBJECTIVE: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity. METHODS: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement. RESULTS: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity. CONCLUSION: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2.


Assuntos
Artrite Juvenil , Reumatologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Consenso , Percepção
18.
J Adolesc ; 96(3): 539-550, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37811912

RESUMO

INTRODUCTION: Adolescents report using digital technologies for emotion regulation (digital ER), with the aim of feeling better (i.e., improving emotions and reducing loneliness). In this 7-day diary study, we investigated associations of digital ER, emotions, and loneliness, and tested whether prior emotional problems moderated these associations. METHOD: Participants were 312 Australian adolescents (Mage = 13.91, SD = 1.52; 44% boys). Daily surveys measured digital ER; end-of-day happiness, sadness, worry, anger, and loneliness; and peak sadness, worry, and anger. End-of day emotions were subtracted from peak emotions to calculate emotion recovery for sadness, worry, and anger. Participants were randomly selected from two symptom strata (high/low) defined by depression and social anxiety measures collected before the diary. Data were analyzed using multilevel path modeling. Cross-level interactions tested whether symptom strata moderated associations. RESULTS: Digital ER was associated with more recovery from peak to end-of-day sadness and worry, but also with increased sadness, worry, anger, and loneliness by the next end-of-day. Higher end-of-day loneliness was associated with increased next-day digital ER. Prior emotional symptoms were not a significant moderator of daily digital ER and emotion associations. CONCLUSION: Adolescents who report more digital ER in a day show more recovery from the peak of negative emotion that day, but this recovery dissipates, with digital ER also associated with increased negative emotion and loneliness by the next day for all adolescents, regardless of prior symptom status. Lonelier adolescents use more digital ER by the next day, suggesting they need support to make social connections-online or offline.


Assuntos
Regulação Emocional , Solidão , Masculino , Adolescente , Humanos , Feminino , Tecnologia Digital , Austrália , Emoções , Ira
19.
Biomol Ther (Seoul) ; 32(1): 38-55, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38148552

RESUMO

Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

20.
Semin Arthritis Rheum ; 64: 152342, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128175

RESUMO

OBJECTIVE: To educate and discuss pain mechanisms (nociceptive, neuropathic, nociplastic) illuminating its possible impact when measuring different outcomes, which may modify, confound and potentially bias the outcome measures applied across various aspects of Rheumatic Musculoskeletal Diseases (RMDs) clinical trials. METHODS: In the plenary presentations, PM lectured on different pain mechanisms and impact on disease activity assessment. Data from two data sets of RMDs patients, which assessed the prevalence and impact of nociplastic pain were presented and reviewed. Audience breakout group sessions and polling were conducted. RESULTS: Mixed pain etiologies may differentially influence disease activity assessment and therapeutic decision-making. Polling demonstrated a consensus on the need to assess different types of pain as a phenotype, as it constitutes an important contextual factor (a variable that is not an outcome of the trial, but needs to be recognized [and measured] to understand the study results), and to standardize across RMDs. CONCLUSION: There is need for a standardized pain measure that can differentiate underlying pain mechanisms.


Assuntos
Dor Crônica , Doenças Musculoesqueléticas , Doenças Reumáticas , Reumatologia , Humanos , Dor Crônica/terapia , Doenças Reumáticas/terapia , Avaliação de Resultados em Cuidados de Saúde
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